carboxamides as Novel Anticancer and Fluorescence Agents … · Supporting Information Preparation of 2-Phenyl-3-Hydroxyquinoline-4(1H)-one-5- carboxamides as Novel Anticancer and

Supporting Information

Preparation of 2-Phenyl-3-Hydroxyquinoline-4(1H)-one-5-

carboxamides as Novel Anticancer and Fluorescence Agents

Petr Funka, Kamil Motykaa, Petr Džubákb, Pawel Znojekb, Sona Gurskab, Joachim Kuszc,

Claire McMastera, Marián Hajdúchb, and Miroslav Sourala

aDepartment of Organic Chemistry, Institute of Molecular and Translational Medicine,

Faculty of Science, Palacký University, 771 46 Olomouc, Czech Republic

bInstitute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry,

Palacky University and University Hospital in Olomouc, Hněvotínská 5, CZ-775 15 Olomouc,

Czech Republic

cInstitute of Physics, University of Silesia, 4 Uniwersytecka Street, Pl-40-007 Katowice, Poland

Table of Contents

General Information………………………………………………………………………………………………………S2

Experimental Procedures…………………………………………………………………………………………......S4

Analytical data……………………………………………………………………………………………………………….S7

Original 1H and 13C NMR Spectra…………………………………………………………………………….....S16

Original HRMS Spectra…………………………………………………………………………………………….....S45

Crystallography data……………………………………………………………………………………….……….....S57

Fluorescent microscop images…………………………………………………………………………………....S61

Electronic Supplementary Material (ESI) for RSC Advances.This journal is © The Royal Society of Chemistry 2015

Material and Methods

Solvents and chemicals were purchased from Aldrich (Milwaukee, IL, www.sigmaaldrich.com), Acros (Geel, Belgium, www.acros.cz) and Fisher (Pittsburgh, PA, www.fishersci.com).

LC/MS analyses were carried out on UHPLC-MS system consisting of UHPLC chromatograph Accela with photodiode array detector and triple quadrupole mass spectrometer TSQ Quantum Access (both Thermo Scientific, CA, USA), using Nucleodur Gravity C18 column at 30°C and flow rate of 800 µL/min (Macherey-Nagel, 1.8 µm, 2.1 x 50 mm, Germany). Mobile phase was (A) 0.01 M amonium acetate in water, and (B) acetonitrile, linearly programmed from 10 % to 80 % B over 2.5 min, kept for 1.5 min. The column was re-equilibrated with 10 % of solution B for 1 min. The APCI source operated at discharge current of 5 µA, vaporizer temperature of 400°C and capillary temperature of 200 oC.

NMR 1H/13C spectra were obtained on a Varian (400 MHz) instrument. NMR spectra were recorded at ambient temperature (21 oC) in DMSO-d6 or TFA-d1 solutions and referenced to the resonance signal of DMSO of TFA. Chemical shifts δ are reported in ppm and coupling constants J in Hz.

HRMS analysis was performed using an Orbitrap Elite high-resolution mass spectrometer (Thermo Fischer Scientific, MA, USA) operating at positive full scan mode (120 000 FWMH) in the range of 200–900 m/z. The settings for electrospray ionization were as follows: oven temperature of 300 °C, sheath gas of 8 arb. units and source voltage of 1.5 kV. The acquired data were internally calibrated with diisooctyl phthalate as a contaminant in methanol (m/z 391.2843). Samples were diluted to a final concentration of 20 μmol/l with 0.1% formic acid in water and methanol (50:50, v/v). The samples were injected by direct infusion into the mass spectrometer.

Crystallography. The single-crystal X-ray experiment was performed at room temperature. For this measurement, colorless single crystal of good quality was preselected under a polarization microscope. The crystal was mounted on a quartz capillary. The data were collected using SuperNova kappa diffractometer with Atlas CCD detector (Agilent Technologies, Yarnton, UK). Accurate cell parameters were determined and refined using CrysAlis CCD program (version 1.171.37.35, Agilent Technologies, Yarnton, UK). For the integration of the collected data, the CrysAlis RED program (version 1.171.37.35, Agilent Technologies) was used.

The structure was solved using direct method with SHELXS-2014 [Sheldrick, 2008] = [Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122] program and then the solution was refined using SHELXL-2014 [Sheldrick, 2008] program. The aromatic hydrogen atoms were treated as “riding” on their parent carbon atoms with d(C H) = 0.93 Å and assigned isotropic atomic displacement parameters equal to 1.2 times the value of the equivalent atomic displacement parameters of the parent carbon atom [Uiso(H) = 1.2Ueq(C)]. The methylene H atoms were constrained to an ideal geometry with d(C H) = 0.97 Å and Uiso(H) = 1.2Ueq(C). Methyl H atoms were constrained as riding atoms, fixed to the parent atoms with distance of 0.96 Å and Uiso(H) = 1.5Ueq(C). Hydrogen atoms involved in H-bonding were introduced into the calculated positions and then refined freely with isotropic atomic displacement parameters.

The crystal structure has been deposited at the Cambridge Crystallographic Data Centre and allocated the deposition number CCDC 1057862.

Cytotoxic MTT assay. Cell suspensions were prepared and diluted according to the particular cell type and the expected target cell density (2 500–30 000 cells/well based on cell growth characteristics). Cells were added by pipette (80 L) into 96-well microtiter plates. Inoculates were allowed a pre-incubation period of 24 h at 37 °C and 5 % CO2 for stabilisation. Four-fold dilutions, in 20-L aliquots, of the intended test concentration were added to the microtiter plate wells at time zero. All test compound concentrations were examined in duplicate. Incubation of the cells with the test compounds lasted for 72 h at 37 °C, in a 5 % CO2 atmosphere at 100 % humidity. At the end of the incubation period, the cells were assayed using MTT. Aliquots (10 L) of the MTT stock solution were pipetted into each well and incubated for a further 1–4 h. After this incubation period the formazan produced was dissolved by the addition of 100 L/well of 10 % aq SDS (pH = 5.5), followed by a further incubation at 37 °C overnight. The optical density (OD) was measured at 540 nm with a Labsystem iEMS Reader MF. Tumour cell survival (TCS) was calculated using the following equation: TCS = (ODdrug-exposed well / mean ODcontrol wells) x 100 %. The IC50 value, the drug concentration lethal to 50 % of the tumour cells, was calculated from appropriate dose-response curves.

Fluorescent microscop assay. U2OS osteosacroma cancer cells were plated into 384 wells PerkinElmer CellCarrier plate in densities 2000 cells per well and left overnight in incubator. Next day live cells were exposed to 10 M compound concentration for 30 min. Live cell images were captured with the aid of Yokogawa CellVoyager7000 automated microscope with 60x water immersion objective. Cells were illuminated with 488 nm and 561 nm lasers and images were acquired respectively with 525/50 nm and 620/70 nm band pass filters

Experimental procedures:Preparation of 2-(methoxycarbonyl)-3-nitrobenzoic acid (2):

3-Nitrophtalic anhydride (10 g) was dissolved in methanol (30 mL) under boiling and subsequently refluxed for 16 hours. Methanol was removed in vacuo and the residue (white solid compound) was recrystallized from water. If the compound purity was insufficient the recrystallization was repeated.

Preparation of 3-amino-2-(methoxycarbonyl)benzoic acid (3):

The compound 2 (0.57 g) and 10% Pd/C (0.057 g) were mixed with methanol (15 mL) and the reaction mixture was kept under the hydrogen atmosphere for 2 hours. The reaction mixture was filtered and evaporated in vacuo. The resulting compound was purified by silica gel column chromatography (Hex:EtOAc 7:3).

Preparation of N-propyl-3-nitrophtalic anhydride (5):

The compound 2 (2 g, 8.9 mmol) was mixed with thionylchloride (10 mL) and the reaction mixture was stirred at 35-40°C to obtain the yellow limpid solution. The mixture is concentrated and the residue dissolved in dry toluene (2 mL) and again concentrated. This process is repeated. The residue (white solid compound) was dissolved in dry THF (15 mL) and added in several portions to the solution of propylamine (0.73 mL, 8.9 mmol) and TEA (1.6 mL, 11.5 mmol) in dry THF (20 mL). After 2 hours of stirring the mixture was diluted with water (50 mL) and extracted with EtAc (3x 25 mL). The combined organic layers were washed with saturated NaHCO3 (aq.), water and brine and finally concentrated in vacuo.

Preparation of 2-nitro-6-(propylcarbamoyl)benzoic acid (6):

The compound 5 (1.5 g) was added to the 10% NaOH solution in methanol (20 mL). The reaction mixture was refluxed for 2 hours and then concentrated in vacuo. The residue was dissolved in water and adjusted to pH 3 with hydrochloric acid. The resulting suspension was filtered and washed with water.

Preparation of dimethyl 3-nitrophthalate (8):

The compound 2 (2 g) was mixed with thionylchloride (8 mL) and the reaction mixture was stirred at 35-40°C until the yellow limpid solution is formed. The evaporation of thionylchloride yielded the white solid compound which was dissolved in methanol (15 mL) and refluxed for 4 hours. The reaction mixture was cooled down to room temperature, diluted with water (30 mL) and extracted with EtAc (3x 15 mL). The combined organic layers were washed with saturated NaHCO3 (aq.), water and brine and concentrated in vacuo to give the white solid compound.

Preparation of dimethyl 3-aminophthalate (9):

The compound 8 (3.5 g) and 10% Pd/C (0.3 g) were mixed with methanol and the reaction mixture was kept under the hydrogen atmosphere for 2 hours. The reaction mixture was filtered and concentrated in vacuo to obtain yellowish viscous liquid.

Preparation of 3-aminophthalic acid (10):

The compound 9 (2 g) was mixed with 10% solution of NaOH in methanol (20 mL). The reaction mixture was refluxed for 2 hours and then concentrated in vacuo. The residue was dissolved in water, adjusted to pH 6 with hydrochloric acid. The resulting suspension was filtered and washed with water.

Preparation of 3-nitrophthalic acid (11):

The compound 8 (2 g) was added to the 10% NaOH solution in methanol (20 mL). The reaction mixture was heated under reflux for 2 hours and concentrated in vacuo. The residue was dissolved in water, adjusted to pH 3 with hydrochloric acid. The yielded suspension was filtered and washed with water.

Preparation of bis(2-oxo-2-phenylethyl) 3-nitrophthalate (12a):

The compound 11 (0.4 g, 1.9 mmol) was added to the solution of TEA (0.58 mL, 4.2 mmol) in DMF (5 mL). After 10 minutes of stirring bromoacetophenone (0.72 g, 3.6 mmol) was added and the reaction mixture was stirred for 2 hours at room temperature. Water was added and the formed precipitation was filtered off and washed with water. The dry crude product was suspended in methanol and filtered.

General synthesis methods of compounds 13a-g

3-Aminophtalic acid (10) (0.4 g, 2.2 mmol) was dissolved in the mixture of TEA (0.675 mL, 4.9 mmol) and DMF (10 mL) and stirred for 10 minutes. The bromoacetophenone (4.2 mmol) was added and the reaction mixture was stirred for 2 hours at room temperature (the precipitation was formed gradually). The reaction mixture was poured into the water (50 mL) and the precipitated compound was filtered off and washed with water thoroughly.Purification of 13a, 13c-e: The dry crude product was suspended in methanol and filtered.Purification of 13b, 13f-g: The dry crude product was suspended in ethanol and filtered.

Preparation of bis(2-(3-nitro-4-(piperidin-1-yl)phenyl)-2-oxoethyl) 3-aminophthalate (13h):

The compound 13g (0.2 g, 0.35 mmol) was dissolved in solution of piperidine (0.42 mL, 4.05 mmol) and DMF (6 mL). The reaction mixture was stirred for 2 hours at room temperature and then poured into the water. The pH was adjusted to 5 with hydrochloric acid and the precipitated compound was filtered off and washed with water.

General synthesis methods of compounds 14a-f

The compound 13a-f (200 mg) was dissolved in trifluoroacetic acid (3 mL) and the reaction mixture was refluxed for 2 hours (6 hours for compound 13b). Trifluoracetic acid was evaporated and the residue was mixed with Et2O, filtered and washed with Et2O. The dry crude product was suspended in solution water:ethanol (1:1), warmed to boiling point, filtered hot and washed with water:ethanol (1:1) and Et2O.

General synthesis methods of compounds 14g-h

The compound 13g-h (0.2 g) was suspended in polyphosphoric acid (3 mL) and the reaction mixture was heated to 100°C. After 6 hours of heating the reaction mixture was poured into the ice-water and the formed crystals were filtered off and washed with water and Et2O. The dry crude product was mixed with water:ethanol (1:1). The suspension was heated to boiling point, filtered hot, washed with water:ethanol (1:1) and Et2O.

General synthesis methods of compounds 15a-f and 15h-i

The compound 14a-f (0.2 g) was dissolved in 10% amine in DMF (2 mL). The reaction mixture was stirred for 2 hours at 50°C. After addition of water the yielded suspension was filtered off and washed with water.Purification of 15a, 15d, 15e, 15h: The dry crude product was dissolved in ethanol, then water was added and the resulting precipitation was filtered off and washed with water.Purification 15b: The dry crude product was shortly boiled in EtAc, filtered and washed with Et2O.

Purification of 15c: The dry crude product was dissolved in EtOH and precipitated with Et2O. The formed suspension was filtered and washed with Et2O. Purification of 15f: The dry crude product was shortly boiled in Et2O and filtered.Purification of 15i: The dry crude product was purified by silica gel column chromatography (EtAc:Tol /1:1).

Preparation of compound 15g

The compound 14b (0.2 g) was mixed with 2-aminoethanol (2 mL) and the reaction mixture was stirred for 2 hours at 50°C. The reaction mixture was poured into water and the resulting precipitation was filtered off and washed with water. The dry crude product was suspended in Et2O, filtered and washed with Et2O.

Preparation of compound 15l

The compound 14b (0.2 g) was mixed with saturated solution of ammonia in methanol (2 mL) and with DMF (2 mL). The reaction mixture was stirred for 2 hours at 50°C, water was added and pH was adjusted to 7 with hydrochloric acid. The formed suspension was filtered off and washed with water. The dry crude product was suspended in methanol, filtered and washed with Et2O.

General synthesis methods of compounds 16a-b

The compound 14 (0.2 g) was mixed with 0.25M NaOH in metanol (6 mL). The reaction mixture was refluxed for 1 hour and cooled down to room temperature. The precipitated crystals were filtered off and washed with small amount of cold methanol.

Analytical data:

2-(Methoxycarbonyl)-3-nitrobenzoic acid (2):Yield 8.32 g (71 %). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.41 (dd, J=1.3, 8.3 Hz, 1 H), 8.32 (dd, J=1.1, 7.7 Hz, 1 H), 7.87 (t, J=7.9 Hz, 1 H), 3.85 (s, 3 H). 13C NMR (101MHz, DMSO-d6) δ ppm 165.4, 165.2, 146.1, 135.7, 131.4, 131.1, 129.4, 128.3, 53.2.

3-Amino-2-(methoxycarbonyl)benzoic acid (3):Yield 0.24 g (48 %). 1H NMR (400MHz, DMSO-d6) δ ppm 7.26 - 7.15 (m, 1 H), 6.87 (dd, J=1.2, 8.2 Hz, 1 H), 6.82 (dd, J=1.2, 7.4 Hz, 1 H), 5.78 (br. s., 2 H), 3.71 (s, 3 H). 13C NMR (101MHz, DMSO-d6) δ ppm 169.3, 168.2, 147.8, 134.5, 131.2, 118.6, 116.1, 113.0, 51.9.

N-Propyl-3-nitrophtalic anhydride (5):Yield 1.41 g (68 %). 1H NMR (400MHz ,DMSO-d6) δ ppm 7.45 - 7.38 (m, 1 H), 7.00 - 6.92 (m, 2 H), 6.44 (br. s., 2 H), 3.45 (t, J=7.2 Hz, 2 H), 1.56 (sxt, J=7.3 Hz, 2 H), 0.84 (t, J=7.5 Hz, 3 H). 13C NMR (101MHz, DMSO-d6) δ ppm 169.5, 168.1, 146.4, 135.0, 132.3, 121.3, 110.6, 108.9, 38.5, 21.4, 11.2.

2-Nitro-6-(propylcarbamoyl)benzoic acid (6):Yield 1.53 g (95 %). 1H NMR (400MHz, DMSO-d6) δ ppm 13.64 (br. s., 1 H), 8.81 - 8.60 (m, 1 H), 8.12 (d, J=7.5 Hz, 1 H), 7.86 (d, J=7.0 Hz, 1 H), 7.73 (t, J=7.9 Hz, 1 H), 3.24 - 3.13 (m, 2 H), 1.51 (sxt, J=7.3 Hz, 2 H), 0.90 (t, J=7.5 Hz, 3 H). 13C NMR (101MHz, DMSO-d6) δ ppm 165.8, 165.6, 147.0, 137.1, 132.5, 130.3, 128.2, 125.1, 41.0, 22.2, 11.4.

Dimethyl 3-nitrophthalate (8):Yield 1.82 g (86 %). 1H NMR (400MHz, DMSO-d6) δ ppm 8.45 (dd, J=1.1, 8.1 Hz, 1 H), 8.34 (dd, J=1.3, 7.9 Hz, 1 H), 7.90 (t, J=8.1 Hz, 1 H), 3.88 (s, 3 H), 3.88 (s, 3 H). 13C NMR (101MHz, DMSO-d6) δ ppm 165.1, 164.1, 146.1, 135.7, 131.6, 129.5, 129.3, 128.8, 53.3.

Dimethyl 3-aminophthalate (9):Yield 3.01 g (98 %). 1H NMR (400MHz, DMSO-d6) δ ppm 7.27 - 7.22 (m, 1 H), 6.92 (dd, J=0.9, 8.3 Hz, 1 H), 6.75 (dd, J=1.1, 7.2 Hz, 1 H), 6.09 (s, 2 H), 3.75 (s, 3 H), 3.74 (s, 3 H). 13C NMR (101MHz, DMSO-d6) δ ppm 168.6, 167.6, 148.7, 133.6, 131.8, 119.0, 115.6, 111.0, 52.3, 52.0.

3-Aminophthalic acid (10):Yield 1.44 g (81 %). 1H NMR (400MHz, DMSO-d6) δ ppm 7.18 (dd, J=7.5, 8.3 Hz, 1 H), 6.84 (dd, J=0.9, 8.3 Hz, 1 H), 6.67 (dd, J=1.1, 7.2 Hz, 1 H). 13C NMR (101MHz, DMSO-d6) δ ppm 170.0, 169.1, 148.7, 135.8, 131.3, 118.1, 115.2, 111.9.

3-Nitrophthalic acid (11):Yield 1.64 g (93 %). 1H NMR (400MHz, DMSO-d6) δ ppm 8.17 (dd, J=1.3, 7.9 Hz, 1 H), 7.86 (dd, J=1.3, 8.3 Hz, 1 H), 7.59 (t, J=7.9 Hz, 1 H). 13C NMR (101MHz, DMSO-d6) δ ppm 166.8, 166.1, 151.0, 134.5, 134.0, 132.9, 129.1, 125.8.

Bis(2-oxo-2-phenylethyl) 3-nitrophthalate (12a):NO2

O

O

O

OO

O

Yield 0,58 g (72 %). 1H NMR (400MHz, DMSO-d6) δ ppm 8.54 (dd, J=1.3, 8.3 Hz, 1 H), 8.49 (dd, J=1.3, 7.9 Hz, 1 H), 8.05 - 7.96 (m, 5 H), 7.75 - 7.65 (m, 2 H), 7.61 - 7.50 (m, 4 H), 5.85 (s, 2 H), 5.68 (s, 2 H). 13C NMR (101MHz, DMSO-d6) δ ppm 191.8, 191.8, 163.9, 163.3, 146.5, 135.7, 134.2, 134.1, 133.9, 133.6, 132.2, 129.3, 129.2, 129.0, 128.9, 128.6, 128.0, 127.9, 68.4, 68.2.

Bis(2-oxo-2-phenylethyl) 3-aminophthalate (13a):

NH2

O

O

O

OO

O

Yield 0.61 g (70 %). 1H NMR (400MHz, DMSO-d6) δ ppm 8.06 - 7.98 (m, 4 H), 7.76 - 7.67 (m, 2 H), 7.63 - 7.54 (m, 4 H), 7.39 - 7.32 (m, 1 H), 7.05 - 6.99 (m, 2 H), 6.29 (br. s., 2 H), 5.71 (s, 2 H), 5.65 (s, 2 H). 13C NMR (101MHz, DMSO-d6) δ ppm 193.5, 192.6, 166.7, 166.5, 148.2, 134.2, 133.9, 133.8, 133.6, 131.6, 131.6, 128.9, 128.9, 127.9, 127.7, 119.5, 116.2, 112.1, 67.2, 67.0. HRMS: Calcd for C24H19NO6 = 417.1212, Found m/z 417.1208.

Bis(2-(4-amino-3,5-dichlorophenyl)-2-oxoethyl) 3-aminophthalate (13b):

NH2

O

O

O

OO

O

NH2

Cl

Cl

Cl

NH2

Cl

Yield 0.83 g (68 %). 1H NMR (400MHz, DMSO-d6) δ ppm 7.90 (s, 2 H), 7.86 (s, 2 H), 7.33 (t, J=8.0 Hz, 1 H), 7.02 - 6.97 (m, 2 H), 6.63 (s, 2 H), 6.58 (s, 2 H), 6.25 (br. s, 2 H), 5.57 (s, 2 H), 5.51 (s, 2 H). 13C NMR (101MHz, DMSO-d6) δ ppm 189.8, 188.9, 166.6, 148.2, 146.3, 146.1, 131.5, 131.5, 128.4, 128.2, 122.3, 121.9, 119.5, 117.4, 117.4, 116.3, 112.6, 66.6, 66.5. HRMS: Calcd for C24H17N3O6 = 582.9871, Found m/z 582.9874.

Bis(2-oxo-2-(p-tolyl)ethyl) 3-aminophthalate (13c):NH2

O

O

O

OO

O

Yield 0.78 g (84 %). 1H NMR (400MHz, DMSO-d6) δ ppm7.95 - 7.86 (m, 4 H), 7.42 - 7.30 (m, 5 H), 7.04 - 7.00 (m, 2 H), 6.28 (br. s, 2 H), 5.66 (s, 2 H), 5.61 (s, 2 H), 2.40 (s, 3 H), 2.40 (s, 3 H). 13C NMR (101MHz, DMSO-d6) δ ppm 193.0, 192.0, 166.6, 166.5, 148.1, 144.7, 144.4, 131.5, 131.5, 131.4, 131.1, 129.4, 129.4, 128.0, 127.8, 119.4, 116.2, 112.3, 67.0, 66.9, 21.2, 21.2. HRMS: Calcd for C26H23NO6 = 445.1525, Found m/z 445,1527.

Bis(2-(4-methoxyphenyl)-2-oxoethyl) 3-aminophthalate (13d):

NH2

O

O

O

OO

O

O

O

Yield 0.65 g (65 %). 1H NMR (400MHz, DMSO-d6) δ ppm 8.03 - 7.95 (m, 4 H), 7.34 (t, J=8.0 Hz, 1 H), 7.13 - 7.07 (m, 4 H), 7.05 - 6.99 (m, 2 H), 6.27 (br. s, 2 H), 5.64 (s, 2 H), 5.58 (s, 2 H), 3.87 (s, 3 H), 3.86 (s, 3 H). 13C NMR (101MHz, DMSO-d6) δ ppm 191.8, 190.8, 166.6, 166.5, 163.8, 163.6, 148.0, 131.4, 131.3, 130.3, 130.1, 126.7, 126.4, 119.4, 116.2, 114.1, 114.1, 112.7, 66.8, 66.7, 55.6, 55.6. HRMS: Calcd for C26H23NO8 = 477.1424, Found m/z 477.1425.

Bis(2-(4-fluorophenyl)-2-oxoethyl) 3-aminophthalate (13e):

NH2

O

O

O

OO

O

F

F

Yield 0.78 g (82 %). 1H NMR (400MHz, DMSO-d6) δ ppm 8.16 - 8.05 (m, 4 H), 7.46 - 7.38 (m, 4 H), 7.38 - 7.31 (m, 1 H), 7.05 - 6.98 (m, 2 H), 6.28 (br. s., 2 H), 5.69 (s, 2 H), 5.63 (s, 2 H). 13C NMR (101MHz, DMSO-d6) δ ppm 192.2, 191.3, 166.8, 166.6, 165.5 (d, J=247 Hz, 1 C), 165,3 (d, J=240 Hz, 1 C), 148.3, 131.7, 131.2, 131.1, 131.0, 130.9, 130.7, 130.5, 130.4, 119.6, 116.3, 116.2, 116.2, 116.0, 115.9, 112.1, 67.1, 67.0. HRMS: Calcd for C24H17F2NO6 = 453.1024, Found m/z 453.1026.

Bis(2-(3-bromophenyl)-2-oxoethyl) 3-aminophthalate (13f):NH2

O

O

O

OO

OBr

Br

Yield 0.92 g (77 %). 1H NMR (400MHz, DMSO-d6) δ ppm 8.17 (t, J=1.8 Hz, 1 H), 8.13 (t, J=1.8 Hz, 1 H), 8.02 (td, J=1.3, 7.9 Hz, 1 H), 7.99 (td, J=1.4, 7.7 Hz, 1 H), 7.95 - 7.89 (m, 2 H), 7.59 - 7.51 (m, 2 H), 7.39 - 7.33 (m, 1 H), 7.03 (dd, J=0.9, 8.3 Hz, 1 H), 6.99 (dd, J=1.1, 7.2 Hz, 1 H), 6.29 (br. s., 2 H), 5.70 (s, 2 H), 5.65 (s, 2 H). 13C NMR (101MHz, DMSO-d6) δ ppm 192.6, 191.8, 166.8, 166.4, 148.5, 136.8, 136.6, 135.9, 135.7, 131.9, 131.8, 131.2, 131.2, 130.5, 130.4, 127.0, 126.9, 122.3, 122.3, 119.6, 116.2, 111.6, 67.2, 67.1. HRMS: Calcd for C24H17Br2NO6 = 572.9423, Found m/z 572.9417.

Bis(2-(4-chloro-3-nitrophenyl)-2-oxoethyl) 3-aminophthalate (13g):

NH2

O

O

O

OO

ONO2

NO2

Cl

Cl

Yield 0.82 g (68 %). 1H NMR (400MHz, DMSO-d6) δ ppm8.63 (d, J=2.2 Hz, 1 H), 8.60 (d, J=2.2 Hz, 1 H), 8.31 - 8.22 (m, 2 H), 8.02 (s, 1 H), 8.00 (s, 1 H), 7.40 - 7.32 (m, 1 H), 7.05 - 7.00 (m, 1 H), 6.98 (dd,

J=0.9, 7.5 Hz, 1 H), 6.29 (br. s, 2 H), 5.72 (s, 2 H), 5.68 (s, 2 H). 13C NMR (101MHz, DMSO-d6) δ ppm 192.0, 191.3, 167.3, 166.8, 149.1, 148.4, 148.4, 134.0, 133.9, 133.1, 133.0, 132.9, 132.9, 132.4, 132.4, 130.7, 130.6, 125.3, 125.2, 120.1, 116.7, 111.6, 67.7, 67.6. HRMS: Calcd for C24H15Cl2N3O10 = 575.0134, Found m/z 575.0134.

Bis(2-(3-nitro-4-(piperidin-1-yl)phenyl)-2-oxoethyl) 3-aminophthalate (13h):

NH2

O

O

O

OO

ONO2

NO2

N

N

Yield 0.21 mg (87 %). 1H NMR (400MHz, DMSO-d6) δ ppm 8.36 (d, J=2.3 Hz, 1 H), 8.33 (d, J=2.3 Hz, 1 H), 8.07 - 8.00 (m, 2 H), 7.37 - 7.30 (m, 3 H), 7.04 - 6.97 (m, 2 H), 6.27 (br. s, 2 H), 5.63 (s, 2 H), 5.57 (s, 2 H), 3.17 (br. s., 8 H), 1.61 (br. s., 12 H). 13C NMR (101MHz, DMSO-d6) δ ppm 190.6, 189.7, 166.7, 166.5, 148.8, 148.7, 148.3, 138.4, 138.4, 132.7, 132.6, 131.6, 127.2, 127.0, 123.5, 123.1, 119.8, 119.8, 119.5, 116.3, 112.3, 66.8, 66.7, 51.1, 51.1, 25.2, 23.2. HRMS: Calcd for C34H35N5O10 = 673.2384, Found m/z 673.2376.

2-Oxo-2-phenylethyl 2-phenyl-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14a):

NH

OOH

O OO

Yield 168 mg (88 %). 1H NMR (400MHz, DMSO-d6) δ ppm 11.84 (s, 1 H), 8.70 (br. s, 1 H), 8.09 - 8.02 (m, 2 H), 7.89 - 7.78 (m, 3 H), 7.76 - 7.65 (m, 2 H), 7.65 - 7.49 (m, 5 H), 7.31 (dd, J=0.9, 7.0 Hz, 1 H), 5.66 (s, 2 H). 13C NMR (101MHz, DMSO-d6) δ ppm 193.1, 169.2, 168.8, 138.4, 138.0, 134.1, 134.0, 132.0, 131.9, 131.6, 130.0, 129.4, 129.3, 129.0, 128.4, 127.9, 120.8, 120.1, 118.1, 67.1. HRMS: Calcd for C24H17NO5 = 399.1107, Found m/z 399.1101.

2-(4-Amino-3,5-dichlorophenyl)-2-oxoethyl 2-(4-amino-3,5-dichlorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14b):

NH

OOH

O OO

H2N

Cl

Cl

NH2

Cl

Cl

Yield 169 mg (87 %). 1H NMR (400MHz, DMSO-d6) δ ppm 11.62 (s, 1 H), 7.90 (s, 2 H), 7.83 (dd, J=0.8, 8.6 Hz, 1 H), 7.79 (s, 2 H), 7.70 - 7.62 (m, 1 H), 7.28 (dd, J=0.8, 7.0 Hz, 1 H), 6.59 (br. s, 2 H), 6.05 (br. s., 2 H), 5.51 (s, 2 H). 13C NMR (101MHz, DMSO-d6) δ ppm 189.3, 169.0, 168.4, 146.0, 142.1, 138.0, 137.8, 131.5, 129.9, 129.6, 128.6, 128.3, 122.4, 120.6, 119.8, 119.7, 117.8, 117.3, 117.3, 66.6. HRMS: Calcd for C24H15Cl4N3O5 = 564.9766 Found m/z 564.9758.

2-Oxo-2-(p-tolyl)ethyl 2-(p-tolyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14c):

NH

OOH

O OO

Yield 178 mg (93 %). 1H NMR (400MHz, TFA-d1) δ ppm 8.94 (d, J=7.4 Hz, 1 H), 8.42 (d, J=8.6 Hz, 1 H), 7.98 (t, J=8.0 Hz, 1 H), 7.93 (d, J=8.6 Hz, 2 H), 7.82 (d, J=8.2 Hz, 2 H), 7.44 (d, J=7.8 Hz, 2 H), 7.38 (d, J=8.2 Hz, 2 H), 5.98 (s, 2 H), 2.45 (s, 3 H), 2.44 (s, 3 H). 13C NMR (101MHz, TFA-d1) δ ppm 197.7, 172.9, 158.1, 151.0, 147.3, 145.8, 140.6, 139.1, 138.2, 133.3, 132.0, 131.9, 131.7, 130.9, 130.4, 129.7, 126.4, 126.0, 118.8, 70.7, 22.2, 21.9. HRMS: Calcd for C26H21NO5 = 427.1420 Found m/z 427.1418.

2-(4-Methoxyphenyl)-2-oxoethyl 2-(4-methoxyphenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14d):

NH

OOH

O OO

O

O

Yield 162 mg (84 %). 1H NMR (400MHz, DMSO-d6) δ ppm 11.71 (s, 1 H), 8.51 (br. s., 1 H), 8.06 - 7.99 (m, 2 H), 7.84 (dd, J=1.0, 8.6 Hz, 1 H), 7.82 - 7.76 (m, 2 H), 7.70 - 7.63 (m, 1 H), 7.30 (dd, J=1.0, 7.0 Hz, 1 H), 7.16 - 7.12 (m, 2 H), 7.12 - 7.08 (m, 2 H), 5.59 (s, 2 H), 3.87 (s, 3 H), 3.85 (s, 3 H). 13C NMR (101MHz, DMSO-d6) δ ppm 191.3, 169.2, 168.5, 163.6, 160.1, 138.0, 137.9, 131.7, 131.7, 130.7, 130.3, 129.8, 127.0, 124.1, 120.7, 119.9, 117.9, 114.2, 113.8, 66.8, 55.6, 55.4. HRMS: Calcd for C26H21NO7 = 459.1318 Found m/z 459.1315.

2-(4-Fluorophenyl)-2-oxoethyl 2-(4-fluorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14e):

NH

OOH

O OO

F

F

Yield 173 mg (90 %). 1H NMR (400MHz, DMSO-d6) δ ppm 11.83 (s, 1 H), 8.67 (br. s., 1 H), 8.18 - 8.10 (m, 2 H), 7.91 - 7.85 (m, 2 H), 7.83 (dd, J=0.9, 7.5 Hz, 1 H), 7.73 - 7.65 (m, 1 H), 7.47 - 7.38 (m, 4 H), 7.30 (dd, J=0.9, 7.0 Hz, 1 H), 5.64 (s, 2 H). 13C NMR (101MHz, DMSO-d6) δ ppm 191.8, 169.1, 168.7, 165.2 (d, J=291 Hz, 1 C), 164.1, 161.3, 162.7 (d, J=287 Hz, 1 C), 138.3, 137.9, 131.7, 131.6, 131.6, 131.1, 131.0, 130.9, 130.9, 130.9, 130.0, 128.3, 128.3, 120.8, 120.0, 118.1, 116.1 (d, J=22 Hz, 1 C), 115.3 (d, J=22 Hz, 1 C), 67.0. HRMS: Calcd for C24H15F2NO5 = 435.0918 Found m/z 435.0919.

2-(3-Bromophenyl)-2-oxoethyl 2-(3-bromophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14f):

NH

OOH

O OO

Br

Br

Yield 184 mg (95 %). 1H NMR (400MHz, DMSO-d6) δ ppm 11.86 (s, 1 H), 8.82 (br. s., 1 H), 8.17 (t, J=1.8 Hz, 1 H), 8.05 (d, J=7.9 Hz, 1 H), 8.00 (t, J=1.8 Hz, 1 H), 7.95 - 7.90 (m, 1 H), 7.84 (s, 1 H), 7.82 (s, 1 H), 7.77 - 7.72 (m, 1 H), 7.72 - 7.65 (m, 1 H), 7.60 - 7.50 (m, 2 H), 7.29 (d, J = 6.1 Hz, 1 H), 5.65 (s, 2 H). 13C NMR (101MHz, DMSO-d6) δ ppm 192.3, 169.1, 168.8, 138.5, 138.0, 136.5, 136.1, 134.1, 132.1, 131.7, 131.5, 131.2, 130.5, 130.4, 130.2, 130.1, 128.5, 127.0, 122.3, 121.5, 120.8, 120.1, 118.1, 67.2. HRMS: Calcd for C24H15Br2NO5 = 554.9317 Found m/z 554.9315.

2-(4-Chloro-3-nitrophenyl)-2-oxoethyl 2-(4-chloro-3-nitrophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14g):

NH

OOH

O OO

Cl

Cl

O2N

NO2

Yield 157 mg (81 %). 1H NMR (400MHz, DMSO-d6) δ ppm 11.97 (s, 1 H), 9.11 (br. s., 1 H), 8.65 (d, J=2.2 Hz, 1 H), 8.53 (d, J=2.2 Hz, 1 H), 8.31 (dd, J=2.0, 8.6 Hz, 1 H), 8.15 (dd, J=2.0, 8.6 Hz, 1 H), 8.03 (s, 1 H), 8.00 (s, 1 H), 7.82 (d, J=8.3 Hz, 1 H), 7.76 - 7.67 (m, 1 H), 7.31 (d, J = 6.6 Hz, 1 H), 5.70 (s, 2 H). 13C NMR (101MHz, DMSO-d6) δ ppm 191.3, 169.0, 147.9, 147.4, 138.9, 138.1, 134.6, 133.7, 132.8, 132.4, 132.1, 131.6, 131.4, 130.5, 130.1, 128.4, 126.2, 125.6, 124.9, 121.0, 120.2, 118.2, 112.1, 67.3. HRMS: Calcd for C24H13Cl2N3O9 = 557.0029 Found m/z 557.0020.

2-(3-Nitro-4-(piperidin-1-yl)phenyl)-2-oxoethyl 2-(3-nitro-4-(piperidin-1-yl)phenyl)- 3-hydroxy-quinoline-4(1H)-one-5-carboxylate (14h):

NH

OOH

O OO

N

N

O2N

NO2

Yield 154 mg (79 %). 1H NMR (400MHz, DMSO-d6) δ ppm 11.78 (s, 1 H), 8.80 (br. s., 1 H), 8.37 (d, J=2.2 Hz, 1 H), 8.28 (d, J=1.3 Hz, 1 H), 8.09 (dd, J=1.8, 8.8 Hz, 1 H), 8.00 (d, J=8.3 Hz, 1 H), 7.82 (d, J=8.3 Hz, 1 H), 7.68 (t, J=7.7 Hz, 1 H), 7.44 (d, J=8.8 Hz, 1 H), 7.35 (d, J=8.8 Hz, 1 H), 7.30 (d, J=7.0 Hz, 1 H), 5.58 (s, 2 H), 3.18 (br. s., 4 H), 3.08 (br. s., 4 H), 1.61 (br. s., 12 H). 13C NMR (101MHz, DMSO-d6) δ ppm 190.2, 169.1, 168.6, 148.7, 146.2, 140.3, 138.5, 138.4, 137.9, 134.3, 132.8, 131.6, 130.1, 129.7, 127.1, 126.7, 123.7, 122.9, 120.8, 120.4, 120.0, 119.9, 118.0, 66.8, 51.8, 51.1, 25.4, 25.2, 23.4, 23.2. HRMS: Calcd for C34H33N5O9 = 655.2278 Found m/z 655.2270

N-Propyl-2-phenyl-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15a):

NH

OOH

HN O

Yield 57 mg (35 %). 1H NMR (400MHz, DMSO-d6) δ ppm 11.54 (s, 1 H), 8.44 (br. s., 1 H), 7.91 (t, J=5.5 Hz, 1 H), 7.82 - 7.78 (m, 2 H), 7.72 (dd, J=0.9, 8.3 Hz, 1 H), 7.61 - 7.50 (m, 4 H), 7.02 (dd, J=1.3, 7.0 Hz, 1 H), 3.24 - 3.14 (m, 2 H), 1.57 (sxt, J=7.3 Hz, 2 H), 0.93 (t, J=7.5 Hz, 3 H). 13C NMR (101MHz, DMSO-d6) δ ppm 169.7, 166.4, 138.1, 138.0, 135.9, 134.0, 131.4, 130.0, 129.8, 129.5, 128.4, 123.0, 120.0, 117.6, 41.3, 22.1, 11.7. HRMS: Calcd for C19H18N2O3 = 322.1317 Found m/z 322.1317.

N-Propyl-2-(4-amino-3,5-dichlorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15b)

NH

OOH

HN O

NH2

Cl

Cl

Yield 64 mg (45 %). 1H NMR (400MHz, DMSO-d6) δ ppm 11.35 (s, 1 H), 7.91 (t, J=5.5 Hz, 1 H), 7.78 (s, 2 H), 7.71 (d, J=8.8 Hz, 1 H), 7.53 (dd, J=7.0, 8.8 Hz, 1 H), 7.00 (d, J=7.0 Hz, 1 H), 6.02 (br. s., 2 H), 3.23 - 3.13 (m, 2 H), 1.56 (sxt, J=7.3 Hz, 2 H), 0.92 (t, J=7.2 Hz, 3 H). 13C NMR (101MHz, DMSO-d6) δ ppm 169.6, 168.9, 141.9, 138.3, 138.0, 137.4, 129.7, 128.4, 128.0, 120.8, 119.9, 118.5, 117.8, 117.4, 41.0, 22.1, 11.6. Calcd for C19H17Cl2N3O3 = 405.0647 Found m/z 405.0644.

N-Propyl-2-(p-tolyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15c):

NH

OOH

HN O

Yield 101 g (64 %). 1H NMR (400MHz, DMSO-d6) δ ppm 12.80 (br. s., 1 H), 8.51 (br. s., 1 H), 8.03 (d, J=8.8 Hz, 1 H), 7.76 (d, J=8.3 Hz, 2 H), 7.68 (t, J=7.0 Hz, 1 H), 7.41 (d, J=7.9 Hz, 1 H), 7.34 (d, J=7.0 Hz, 1 H), 3.32 - 3.19 (m, 2 H), 2.42 (s, 3 H), 1.59 (sxt, J=7.3 Hz, 2 H), 0.94 (t, J=7.5 Hz, 3 H). 13C NMR (101MHz, DMSO-d6) δ ppm 169.7, 165.1, 139.8, 137.9, 137.7, 135.5, 135.3, 130.0, 129.5, 128.9, 128.2, 123.7, 120.4, 117.4, 41.4, 22.1, 21.1, 11.7. Calcd for C20H20N2O3 = 336.1474 Found m/z 336.1464.

N-Propyl-2-(4-Methoxyphenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15d):

NH

OOH

HN O

O

Yield 62 mg (40 %). 1H NMR (400MHz, DMSO-d6) δ ppm 12.21 (br. s., 1 H), 8.27 (br. s., 1 H), 7.90 (dd, J=0.9, 8.8 Hz, 1 H), 7.84 - 7.78 (m, 2 H), 7.66 - 7.57 (m, 1 H), 7.21 (dd, J=0.9, 7.0 Hz, 1 H), 7.17 - 7.11 (m, 2 H), 3.85 (s, 3 H), 3.28 - 3.17 (m, 2 H), 1.65 - 1.51 (m, 1 H), 0.93 (t, J=7.2 Hz, 3 H). 13C NMR (101MHz, DMSO-d6) δ ppm 169.7, 166.6, 160.3, 138.0, 137.8, 136.1, 133.3, 130.9, 129.8, 123.6, 122.5, 119.7, 117.6, 113.8, 55.4, 41.3, 22.1, 11.7. Calcd for C20H20N2O4 = 352.1423 Found m/z 352.1412.

N-Propyl-2-(4-fluorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15e):

NH

OOH

HN O

F

Yield 48 g (31 %). 1H NMR (400MHz, DMSO-d6) δ ppm 11.55 (br. s., 1 H), 7.92 (t, J=4.8 Hz, 1 H), 7.86 (dd, J=5.7, 8.8 Hz, 2 H), 7.71 (d, J=8.3 Hz, 1 H), 7.55 (t, J=7.5 Hz, 1 H), 7.48 - 7.35 (m, 2 H), 7.02 (d, J=6.6 Hz, 1 H), 3.20 (q, J=6.1 Hz, 2 H), 1.57 (sxt, J=7.3 Hz, 2 H), 0.93 (t, J=7.2 Hz, 3 H). 13C NMR (101MHz, DMSO-d6 ) δ ppm 169.7, 169.3, 162.4 (d, J=247, 1 C), 138.4, 138.3, 137.5, 131.6, 131.5,

129.9, 129.3, 128.5, 121.0, 118.7, 118.1, 115.4, 115.2, 41.1, 22.2, 11.7. Calcd for C19H17FN2O3 = 340.1223 Found m/z 340.1221.

N-Propyl-2-(3-bromophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15f):

NH

OOH

HN O

Br

Yield 125 mg (81 %). 1H NMR (400MHz, DMSO-d6) δ ppm 11.56 (s, 1 H), 8.63 (br. s., 1 H), 7.99 (s, 1 H), 7.92 (t, J=5.5 Hz, 1 H), 7.82 (d, J=7.5 Hz, 1 H), 7.77 - 7.65 (m, 2 H), 7.61 - 7.48 (m, 2 H), 7.02 (d, J=6.6 Hz, 1 H), 3.20 (q, J=6.6 Hz, 1 H), 1.57 (sxt, J=7.3 Hz, 2 H), 0.93 (t, J=7.5 Hz, 3 H). 13C NMR (101MHz, DMSO-d6) δ = 169.6, 169.4, 138.5, 138.5, 137.6, 134.3, 131.9, 131.5, 130.5, 130.0, 128.4, 128.3, 121.5, 121.0, 118.7, 118.1, 41.1, 22.2, 11.7. Calcd for C19H17BrN2O3 = 400.0423 Found m/z 400.0413.

N-(2-Hydroxyethyl)-2-(4-amino-3,5-dichlorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15g):

NH

OOH

HN O

HO

Cl

NH2Cl

Yield 20 mg (35 %). 1H NMR (400MHz, DMSO-d6) δ ppm 11.47 (s, 1 H), 8.50 (br. s., 1 H), 7.92 (t, J=5.7 Hz, 1 H), 7.79 (s, 2 H), 7.73 (dd, J=0.9, 8.8 Hz, 1 H), 7.59 - 7.50 (m, 1 H), 7.04 (dd, J=0.9, 7.0 Hz, 1 H), 6.04 (s, 2 H), 4.71 (br. s., 1 H), 3.60 (t, J=6.1 Hz, 2 H), 3.32 (t, J=6.1 Hz, 2 H). 13C NMR (101MHz, DMSO) δ ppm 169.9, 168.9, 142.0, 138.1, 138.0, 137.0, 129.7, 128.6, 128.5, 120.9, 119.7, 118.7, 117.7, 117.4, 59.8, 42.0. Calcd for C18H15Cl2N3O4 = 407.0440 Found m/z 407.0431.

N-(2-(Piperidin-1-yl)ethyl)-2-(4-amino-3,5-dichlorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15h):

NH

OOH

HN O

N

Cl

NH2Cl

Yield 41 mg (24 %). 1H NMR (400MHz, DMSO-d6) ppm 11.35 (s, 1 H), 8.08 - 7.76 (m, 2 H), 7.69 (d, J=7.9 Hz, 1 H), 7.47 (t, J=7.7 Hz, 1 H), 6.99 (d, J=6.6 Hz, 1 H), 5.95 (br. s., 2 H), 3.67 - 3.20 (m, 6 H), 2.65 - 2.52 (m, 2 H), 1.63 - 1.44 (m, 4 H), 1.44 - 1.28 (m, 2 H). 13C NMR (101MHz, DMSO-d6) ppm 170.4, 142.3, 142.2, 142.2, 142.1, 138.7, 138.6, 137.2, 129.5, 128.9, 121.3, 118.4, 117.9, 117.9, 57.7, 54.3, 40.6, 31.1, 26.8. Calcd for C23H24Cl2N4O3 = 474.1225 Found m/z 474.1223.

N-Benzyl-2-(4-amino-3,5-dichlorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15i):

NH

OOH

HN O

NH2

Cl

Cl

Yield 55 mg (34 %). 1H NMR (400MHz, DMSO-d6) ppm 11.39 (s, 1 H), 8.49 (t, J = 5.9 Hz, 1 H), 7.80 (s, 2 H), 7.74 (d, J=7.9 Hz, 1 H), 7.60 - 7.51 (m, 1 H), 7.46 (d, J=7.0 Hz, 2 H), 7.34 (t, J=7.7 Hz, 2 H), 7.29 - 7.21 (m, 1 H), 7.07 (d, J = 6.6 Hz, 1 H), 6.03 (br. s, 2 H), 4.49 (d, J=6.1 Hz, 2 H). 13C NMR (101MHz, DMSO-d6) ppm 169.7, 168.9, 142.0, 139.8, 138.3, 138.0, 136.9, 128.8, 128.4, 128.1, 128.1, 127.2, 126.4, 120.9, 119.8, 118.7, 117.8, 117.4, 42.5. Calcd for C23H17Cl2N3O3 = 453.0647 Found m/z 4530637.

2-(4-Amino-3,5-dichlorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15l):

NH

OOH

H2N O

NH2

Cl

Cl

Yield 39 mg (30 %). 1H NMR (400MHz, DMSO-d6) ppm 11.34 (s, 1 H), 7.79 (s, 2 H), 7.70 (d, J=8.8 Hz, 1 H), 7.58 - 7.49 (m, 1 H), 7.44 (br. s., 1 H), 7.18 (br. s., 1 H), 7.03 (d, J = 6.1 Hz, 1 H), 6.03 (s, 2 H). 13C NMR (101MHz, DMSO-d6) ppm 171.6, 169.0, 142.0, 138.4, 138.0, 137.5, 129.8, 128.5, 128.0, 120.7, 119.9, 118.5, 117.5, 117.5. Calcd for C16H11Cl2N3O3 = 363.0177 Found m/z 363,0175.

Methyl 2-phenyl-3-hydroxyquinoline-4(1H)-one-5-carboxylate (16a)

NH

OOH

O O

Yield 50 mg (34 %). 1H NMR (400MHz, DMSO-d6) ppm 11.76 (br. s., 1 H), 8.59 (br. s., 1 H), 7.82 - 7.78 (m, 3 H), 7.64 - 7.48 (m, 4 H), 7.18 (dd, J=0.9, 7.0 Hz, 1 H), 3.84 (s, 3 H). 13C NMR (101MHz, DMSO-d6) ppm 170.3, 168.8, 138.3, 138.0, 132.2, 132.0, 131.6, 129.8, 129.3, 129.2, 128.3, 120.2, 119.8, 118.1, 52.0. Calcd for C17H13NO4 = 295.0845 Found m/z 295.0843.

Methyl 2-(4-amino-3,5-dichlorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (16b)

NH

OOH

O O

NH2

Cl

Cl

Yield 43 mg (32 %). 1H NMR (400MHz, DMSO-d6) ppm 11.56 (br. s., 1 H), 7.82 - 7.75 (m, 3 H), 7.63 - 7.55 (m, 1 H), 7.15 (d, J=6.6 Hz, 1 H), 6.02 (s, 2 H), 3.83 (s, 3 H). 13C NMR (101MHz, DMSO-d6) ppm 170.3, 168.5, 142.1, 138.1, 137.9, 132.2, 129.8, 129.5, 128.6, 120.1, 119.9, 119.8, 118.0, 117.4, 52.0. Calcd for C17H12Cl2N2O4 = 378.0174 Found m/z 378.0131.

Original 1H and 13C NMR spectra

Bis(2-oxo-2-phenylethyl) 3-nitrophthalate (12a):

pfMS_NO2_DIFE_PROTON_01

Chemical Shift (ppm)8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5

Nor

mal

ized

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

NO2

O

O

O

OO

O

pfMS_NO2_DIFE_CARBON_01

Chemical Shift (ppm)190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40

Nor

mal

ized

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

NO 2

O

O

O

OO

O

Bis(2-oxo-2-phenylethyl) 3-aminophthalate (13a):

pfMS_ADIFE02_PROTON_01

Chemical Shift (ppm)8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5

Nor

mal

ized

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

NH2

O

O

O

OO

O

pfMS_ADIFE02_CARBON_01

Chemical Shift (ppm)190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40

Nor

mal

ized

Inte

nsity

0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

0.55

NH2

O

O

O

OO

O

Bis(2-(4-amino-3,5-dichlorophenyl)-2-oxoethyl) 3-aminophthalate (13b):

pfMS_ADIFE_08_PROTON_01

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5Chemical Shift (ppm)

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH2

O

O

O

OO

O

NH2

Cl

Cl

Cl

NH2

Cl

NH2

O

O

O

OO

O

NH2

Cl

Cl

Cl

NH2

Cl

pfMS_ADIFE_08_CARBON_01

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40Chemical Shift (ppm)

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

Bis(2-oxo-2-(p-tolyl)ethyl) 3-aminophthalate (13c):

pfMS_ADIF_03_PROTON_01


0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH2

O

O

O

OO

O

NH2

O

O

O

OO

O

pfMS_ADIF_03_CARBON_01

180 160 140 120 100 80 60 40 20Chemical Shift (ppm)

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

Bis(2-(4-methoxyphenyl)-2-oxoethyl) 3-aminophthalate (13d):

pfMS-ADIFE_OH_PROTON_01


0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH2

O

O

O

OO

O

O

O

NH2

O

O

O

OO

O

O

O

pfMS-ADIFE_OH_CARBON_01


0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

Bis(2-(4-fluorophenyl)-2-oxoethyl) 3-aminophthalate (13e):

pfMS-DIFE05_PROTON_02

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5Chemical Shift (ppm)

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH2

O

O

O

OO

O

F

F

NH2

O

O

O

OO

O

F

F

pfMS-DIFE05_CARBON_01


0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

Bis(2-(3-bromophenyl)-2-oxoethyl) 3-aminophthalate (13f):

pfMS_ADIFE06_PROTON_01


0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH2

O

O

O

OO

OBr

Br

NH2

O

O

O

OO

OBr

Br

pfMS_ADIFE06_CARBON_01


0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

Bis(2-(4-chloro-3-nitrophenyl)-2-oxoethyl) 3-aminophthalate (13g):

pfMS_ADIFE_07_PROTON_01

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5Chemical Shift (ppm)

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH2

O

O

O

OO

ONO2

NO2

Cl

Cl

NH2

O

O

O

OO

ONO2

NO2

Cl

Cl

pfMS_ADIFE_07_CARBON_01


0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

0.55

Nor

mal

ized

Inte

nsity

Bis(2-(3-nitro-4-(piperidin-1-yl)phenyl)-2-oxoethyl) 3-aminophthalate (13h):

ADIFE-09_PROTON_01

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5Chemical Shift (ppm)

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH2

O

O

O

OO

ONO2

NO2

N

N

NH2

O

O

O

OO

ONO2

NO2

N

N

ADIFE-09_CARBON_01


0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

0.55

Nor

mal

ized

Inte

nsity

2-Oxo-2-phenylethyl 2-phenyl-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14a):

pfMS_02_Q5_FE_PROTON_01

12 11 10 9 8 7 6 5 4 3 2Chemical Shift (ppm)

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

O OO

NH

OOH

O OO

pfMS_02_Q5_FE_CARBON_01


0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

0.55

Nor

mal

ized

Inte

nsity

2-(4-Amino-3,5-dichlorophenyl)-2-oxoethyl 2-(4-amino-3,5-dichlorophenyl)- hydroxyquinoline-4(1H)-one-5-carboxylate (14b):



0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

O OO

NH2

Cl

Cl

NH2

Cl

Cl

NH

OOH

O OO

NH2

Cl

Cl

NH2

Cl

Cl



0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

Nor

mal

ized

Inte

nsity

2-Oxo-2-(p-tolyl)ethyl 2-(p-tolyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14c):

pfMS-03-Q5-Fe_TFA_PROTON_01

11 10 9 8 7 6 5 4 3 2Chemical Shift (ppm)

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

O OO

NH

OOH

O OO

pfMS-03-Q5-Fe_TFA_CARBON_01

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20Chemical Shift (ppm)

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

2-(4-Methoxyphenyl)-2-oxoethyl 2-(4-methoxyphenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14d):

pfMS_O4_Q5_FE_PROTON_01


0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

O OO

O

O

NH

OOH

O OO

O

O

pfMS_O4_Q5_FE_CARBON_01

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

Nor

mal

ized

Inte

nsity

2-(4-Fluorophenyl)-2-oxoethyl 2-(4-fluorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14e):



0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

O OO

F

F

NH

OOH

O OO

F

F



0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

Nor

mal

ized

Inte

nsity

2-(3-Bromophenyl)-2-oxoethyl 2-(3-bromophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14f):



0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

O OO

Br

Br

NH

OOH

O OO

Br

Br



0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

Nor

mal

ized

Inte

nsity

2-(4-Chloro-3-nitrophenyl)-2-oxoethyl 2-(4-chloro-3-nitrophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14g):



0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

O OO

Cl

Cl

O2N

NO2

NH

OOH

O OO

Cl

Cl

O2N

NO2



0

0.05

0.10

0.15

0.20

0.25

Nor

mal

ized

Inte

nsity



12 11 10 9 8 7 6 5 4 3 2 1Chemical Shift (ppm)

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

O OO

N

N

O2N

NO2

NH

OOH

O OO

N

N

O2N

NO2



0

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0.08

0.09

0.10

Nor

mal

ized

Inte

nsity


pfMS02-Q5-02_PROTON_01


0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

NH O

NH

OOH

NH O

pfMS_Q5_AM_CARBON_01


0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

Nor

mal

ized

Inte

nsity

N-Propyl-2-(4-amino-3,5-dichlorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15b)

pfMS_08_Q5_02_PROTON_01


0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

NH O

NH2

Cl

Cl

NH

OOH

NH O

NH2

Cl

Cl

pfMS_08_Q5_02_CARBON_01


0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

Nor

mal

ized

Inte

nsity

N-Propyl-2-(p-tolyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15c):


13 12 11 10 9 8 7 6 5 4 3 2 1Chemical Shift (ppm)

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

NH O

NH

OOH

NH O

pfMS03-Q5-02_CARBON_01


0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

Nor

mal

ized

Inte

nsity

N-Propyl-2-(4-Methoxyphenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15d):



0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

NH O

O

NH

OOH

NH O

O

pfMS04-Q5-02_CARBON_01


0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

Nor

mal

ized

Inte

nsity

N-Propyl-2-(4-fluorophenyl)- 3-hydroxyquinoline-4(1H)-one-5-carboxamide (15e):



0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

NH O

F

NH

OOH

NH O

F



0.05

0.10

0.15

0.20

0.25

0.30

Nor

mal

ized

Inte

nsity

N-Propyl-2-(3-bromophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15f):



0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

NH O

Br



0

0.05

0.10

0.15

0.20

Nor

mal

ized

Inte

nsity

NH

OOH

NH O

Br

N-(2-Hydroxyethyl)-2-(4-amino-3,5-dichlorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15g):

08-Q5-03_PROTON_01


0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

NH OOH

Cl

NH2

Cl

NH

OOH

NH OOH

Cl

NH2

Cl

08-Q5-03_CARBON_01

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

Nor

mal

ized

Inte

nsity




0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

NH ON

Cl

NH2

Cl



0

0.05

0.10

0.15

Nor

mal

ized

Inte

nsity

N-Benzyl-2-(4-amino-3,5-dichlorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15i):



0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

NH O

NH2

Cl

Cl

NH

OOH

NH O

NH2

Cl

Cl


170 160 150 140 130 120 110 100 90 80 70 60 50 40Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

Nor

mal

ized

Inte

nsity



Chemical Shift (ppm)11 10 9 8 7 6 5 4 3

Nor

mal

ized

Inte

nsity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

NH

OOH

NH2 O

NH2

Cl

Cl

NH

OOH

NH2 O

NH2

Cl

Cl


Chemical Shift (ppm)170 160 150 140 130 120 110 100 90 80 70 60 50 40

Nor

mal

ized

Inte

nsity

0

0.05

0.10

0.15

0.20

0.25

Methyl 2-phenyl-3-hydroxyquinoline-4(1H)-one-5-carboxylate (16a)

pfMS_02_Q5_Me_PROTON_01


0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

O O

NH

OOH

O O

pfMS_02_Q5_Me_CARBON_01


0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

Methyl 2-(4-amino-3,5-dichlorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (16b)

pfMS_08_Q5_Me_PROTON_01


0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Nor

mal

ized

Inte

nsity

NH

OOH

O O

NH2

Cl

Cl

NH

OOH

O O

NH2

Cl

Cl

pfMS_08_Q5_Me_CARBON_01


0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

0.55

0.60

Nor

mal

ized

Inte

nsity

Original HRMS spectra

Bis(2-oxo-2-phenylethyl) 3-aminophthalate (13a):20150306_ADIFE-02 #1-30 RT: 0.01-0.27 AV: 30 NL: 3.25E5T: FTMS + c ESI Full ms [393.00-443.00]

417.8 418.0 418.2 418.4 418.6 418.8 419.0 419.2 419.4 419.6 419.8 420.0 420.2 420.4 420.6m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

90

95

100

Rel

ativ

e A

bund

ance

418.1281

418.8781

419.1314

417.9973

419.3151

419.6784419.1257

419.8818 420.1799 420.3184419.0963418.8599 419.9926419.2764418.2651417.9500 418.6706

418.1642

418.3513 419.6598 419.8607419.3727 420.5606

418.9146

420.4248

Bis(2-(4-amino-3,5-dichlorophenyl)-2-oxoethyl) 3-aminophthalate (13b):20150306_ADIFE-08 #1-30 RT: 0.00-0.31 AV: 30 NL: 1.43E5T: FTMS + c ESI Full ms [558.00-608.00]

583.0 583.5 584.0 584.5 585.0 585.5 586.0 586.5 587.0 587.5 588.0 588.5 589.0 589.5 590.0 590.5m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

90

95

100

Rel

ativ

e A

bund

ance

585.9917

583.9947

585.1722

587.9887

586.9951

584.9982

586.1755588.9921

587.1679 589.9857

584.3714583.2310 589.9630589.4077589.1650

587.9669584.8732 585.2886 588.1617 590.3758586.8289586.2917 588.9696587.3143 589.4830585.6710583.3093 587.8309590.0211583.6250

Bis(2-oxo-2-(p-tolyl)ethyl) 3-aminophthalate (13c):20150306_ADIFE-03 #1-30 RT: 0.01-0.28 AV: 30 NL: 1.81E5T: FTMS + c ESI Full ms [300.00-550.00]

443 444 445 446 447 448 449 450 451 452 453m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

90

95

100

Rel

ativ

e A

bund

ance

446.1600

447.1635

450.2315

450.7332 452.8687444.8696

446.7028442.9344448.1670445.8163444.8445 447.2044 451.2351 451.7114 452.9809450.1314449.1546445.1523

446.3180

442.8474 452.2131448.3112443.9101443.1596 444.3871

Bis(2-(4-methoxyphenyl)-2-oxoethyl) 3-aminophthalate (13d):20150306_ADIFE-04 #1-30 RT: 0.01-0.28 AV: 30 NL: 4.17E5T: FTMS + c ESI Full ms [300.00-550.00]

474 475 476 477 478 479 480 481 482 483 484 485 486 487 488 489 490m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

90

95

100

Rel

ativ

e A

bund

ance

478.1498

479.1532

481.1283 489.1348

489.6363475.1890 481.6300 488.1183473.1033 477.1858 479.2537 484.1158480.1563 488.6202476.7132 490.1376482.1316 485.3237480.2084474.3482 487.3607485.8254478.1881475.3254 477.2380 484.0708473.6412

Bis(2-(4-fluorophenyl)-2-oxoethyl) 3-aminophthalate (13e):20150306_ADIFE-05 #1-30 RT: 0.00-0.28 AV: 30 NL: 1.81E5T: FTMS + c ESI Full ms [300.00-550.00]

451.0 451.5 452.0 452.5 453.0 453.5 454.0 454.5 455.0 455.5 456.0 456.5 457.0 457.5 458.0 458.5 459.0 459.5 460.0m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

90

95

100

Rel

ativ

e A

bund

ance

454.1099

455.1133

450.6777454.2064

454.8656451.1794 452.8686456.8630

456.1166453.1022 455.6865 458.8608451.6813455.2100451.2226

458.0813457.2718 459.1656456.7046453.8723452.7135 454.2778 460.1184451.1347

Bis(2-(3-bromophenyl)-2-oxoethyl) 3-aminophthalate (13f):20150306_ADIFE-06 #1-31 RT: 0.00-0.26 AV: 31 NL: 5.10E4T: FTMS + c ESI Full ms [548.00-598.00]

572.5 573.0 573.5 574.0 574.5 575.0 575.5 576.0 576.5 577.0 577.5 578.0 578.5 579.0 579.5 580.0m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

90

95

100

Rel

ativ

e A

bund

ance

575.9469

573.9490577.9448

576.9503

574.9524 578.9483573.1516

573.4330 578.3208577.2565576.3837573.9692 579.2532575.4119

576.8852

574.9392573.9315 579.9180

574.9747

572.4489 576.1994573.1169 577.9213 578.3430578.8437

Bis(2-(4-chloro-3-nitrophenyl)-2-oxoethyl) 3-aminophthalate (13g):20150306_ADIFE-07 #1-30 RT: 0.01-0.31 AV: 30 NL: 3.20E4T: FTMS + c ESI Full ms [551.00-601.00]

575.5 576.0 576.5 577.0 577.5 578.0 578.5 579.0 579.5 580.0 580.5 581.0 581.5m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

90

95

100

Rel

ativ

e A

bund

ance

576.0194

578.0163

577.0229

579.0198

576.3828 580.0135578.3205577.3699576.8845 581.3641575.4106 577.9446 578.9625 580.9589579.5329575.9458 576.1987 579.1724578.3407577.2344576.5057 580.0311579.9264575.6630 580.5325

578.0823

581.5299577.6608

Bis(2-(3-nitro-4-(piperidin-1-yl)phenyl)-2-oxoethyl) 3-aminophthalate (13h):20150306_ADIFE-09 #1-30 RT: 0.01-0.31 AV: 30 NL: 1.57E6T: FTMS + c ESI Full ms [649.00-699.00]

673.0 673.5 674.0 674.5 675.0 675.5 676.0 676.5 677.0 677.5 678.0 678.5 679.0 679.5 680.0m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

90

95

100

Rel

ativ

e A

bund

ance

674.2449

675.2477

676.2505

677.2535 677.4586675.6751 678.2155 678.4770 679.2180 679.4361676.6786673.2341 680.2102673.4823 675.9601

2-Oxo-2-phenylethyl 2-phenyl-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14a):20150306_02-Q5-FE #1-30 RT: 0.01-0.31 AV: 30 NL: 1.92E6T: FTMS + c ESI Full ms [375.00-425.00]

398.5 399.0 399.5 400.0 400.5 401.0 401.5 402.0 402.5 403.0 403.5 404.0 404.5 405.0 405.5m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

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75

80

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95

100

Rel

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400.1174

401.1204

402.1233398.6902 399.1918 403.2792400.8238 403.7809401.2387399.6934 401.5136 402.3857 404.9605402.8203 404.0247400.4142 405.2237404.5888 405.7686

2-(4-Amino-3,5-dichlorophenyl)-2-oxoethyl 2-(4-amino-3,5-dichlorophenyl)- hydroxyquinoline-4(1H)-one-5-carboxylate (14b):20150306_08-Q5-FE #30 RT: 0.35 AV: 1 NL: 1.04E4T: FTMS + c ESI Full ms [540.00-590.00]

565.5 566.0 566.5 567.0 567.5 568.0 568.5 569.0 569.5 570.0 570.5m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

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95

100

Rel

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e A

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ance

567.9886

569.9854

567.9786

565.9831

568.1642

567.6626568.9923

566.6646 569.3134 569.9749

568.2543567.1661

568.4777567.2968566.0330 567.7857565.6342 566.9859 568.9813 569.1642

566.7870

570.4572566.2863 570.3159569.3634568.7849 569.9490565.6566 570.1588569.4529567.3559566.4987 570.4843

2-Oxo-2-(p-tolyl)ethyl 2-(p-tolyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14c):20150306_03-Q5-FE #1-30 RT: 0.00-0.33 AV: 30 NL: 8.66E5T: FTMS + c ESI Full ms [403.00-453.00]

427.0 427.5 428.0 428.5 429.0 429.5 430.0 430.5 431.0 431.5m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

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95

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Rel

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428.1491

429.1521

430.1552429.2174429.7192426.5806 431.7999429.3183427.0822 431.1394430.2211427.2814 427.5838 428.7731427.9469 430.8011430.1399 431.2799428.2714

428.9096

2-(4-Methoxyphenyl)-2-oxoethyl 2-(4-methoxyphenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14d):20150306_04-Q5-FE #1-30 RT: 0.01-0.31 AV: 30 NL: 2.59E6T: FTMS + c ESI Full ms [435.00-485.00]

460.0 460.5 461.0 461.5 462.0 462.5 463.0 463.5 464.0 464.5m/z

0

5

10

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25

30

35

40

45

50

55

60

65

70

75

80

85

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95

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Rel

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460.1388

461.1417

462.1444

463.1467462.2088 464.3394462.9385 463.6182 464.1493461.6754 461.8388459.7039 460.7906 462.5830460.5511 461.5161

2-(4-Fluorophenyl)-2-oxoethyl 2-(4-fluorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14e):20150306_05-Q5-FE #1-30 RT: 0.01-0.29 AV: 30 NL: 3.46E6T: FTMS + c ESI Full ms [411.00-461.00]

435.0 435.5 436.0 436.5 437.0 437.5 438.0 438.5 439.0 439.5 440.0 440.5m/z

0

5

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30

35

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55

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65

70

75

80

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95

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Rel

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436.0992

437.1022

438.1050

439.1075437.2352 438.1651 439.2909 440.5706435.2714 438.6845 440.0068439.7926437.7685435.0912 435.6547 436.6965436.5278436.9240

2-(3-Bromophenyl)-2-oxoethyl 2-(3-bromophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14f):20150306_06-Q5-FE #1-30 RT: 0.01-0.31 AV: 30 NL: 1.24E6T: FTMS + c ESI Full ms [530.00-580.00]

555.5 556.0 556.5 557.0 557.5 558.0 558.5 559.0 559.5 560.0 560.5 561.0 561.5 562.0 562.5m/z

0

5

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25

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45

50

55

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65

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75

80

85

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95

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Rel

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557.9364

555.9388 559.9342

558.9394

556.9421 560.9371

561.9399557.4382 561.3959557.9499 558.4411 562.3991556.4418 562.8583555.3494 559.3802

561.1386559.6604556.2081560.3083

557.1986

560.6291556.6698555.6116

2-(4-Chloro-3-nitrophenyl)-2-oxoethyl 2-(4-chloro-3-nitrophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (14g):20150306_07-Q5-FE #1-30 RT: 0.01-0.30 AV: 30 NL: 1.24E5T: FTMS + c ESI Full ms [530.00-580.00]

557.5 558.0 558.5 559.0 559.5 560.0 560.5 561.0 561.5 562.0 562.5 563.0 563.5 564.0m/z

0

5

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Rel

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558.0093

560.0063

559.0128

561.3962557.9362 561.0097

562.0033559.9340561.3753 562.3996 563.3754558.9396558.4413

558.2703

563.0066559.2275 560.9374 561.3390 563.4635 564.0182559.4177 561.9851561.4479

560.1307 562.6554559.8796

562.3420557.4535 558.8774

557.8712



N-Propyl-2-(4-amino-3,5-dichlorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15b):

N-Propyl-2-(p-tolyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15c):20150306_03-Q5-02 #1-30 RT: 0.00-0.22 AV: 30 NL: 1.68E7T: FTMS + c ESI Full ms [312.00-362.00]

336.5 337.0 337.5 338.0 338.5 339.0 339.5 340.0 340.5 341.0 341.5 342.0 342.5m/z

0

5

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Rela

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337.1537

338.1565

339.1596338.3403336.9740 338.9682 340.1624 341.9743339.3434 340.8630 341.2643337.9863 342.5851336.7479 339.9199336.4068 337.5613 340.3556

337.3579341.5726

N-Propyl-2-(4-Methoxyphenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15d):20150306_04-Q5-02 #1-31 RT: 0.00-0.22 AV: 31 NL: 1.97E7T: FTMS + c ESI Full ms [328.00-378.00]

352.0 352.5 353.0 353.5 354.0 354.5 355.0 355.5 356.0 356.5 357.0 357.5 358.0m/z

0

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50

55

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65

70

75

80

85

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95

100

Rela

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353.1485

354.1513

355.1541351.9688 356.1561355.0306353.9645352.2757 357.9140352.7124 355.9179353.5852

352.9302356.9113 357.1453355.1846

353.4220354.7897 356.5544 357.6194

354.2831

N-Propyl-2-(4-fluorophenyl)- 3-hydroxyquinoline-4(1H)-one-5-carboxamide (15e):20150306_05-Q5-02 #1-30 RT: 0.00-0.28 AV: 30 NL: 1.01E7T: FTMS + c ESI Full ms [316.00-366.00]

339.5 340.0 340.5 341.0 341.5 342.0 342.5 343.0 343.5 344.0 344.5 345.0m/z

0

5

10

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45

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55

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65

70

75

80

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95

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Rel

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341.1294

342.1323

343.1353342.9160339.3567 344.8863344.0578339.9848 344.5615339.5529 343.5537341.9853340.7163340.3517 341.5439 345.0632342.6424

341.3368340.9372 342.3404

N-Propyl-2-(3-bromophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15f):20150306_06-Q5-02 #1-30 RT: 0.01-0.25 AV: 30 NL: 1.14E6T: FTMS + c ESI Full ms [376.00-426.00]

401.0 401.5 402.0 402.5 403.0 403.5 404.0 404.5 405.0 405.5 406.0 406.5 407.0 407.5 408.0m/z

0

5

10

15

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65

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Rel

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401.0486403.0464

402.0518 404.0494

401.0326403.0621 405.0615

406.5906402.0348400.8239 404.0116 404.0660 406.0649 407.0923 407.5477402.8512401.2654 402.3567 405.2234 407.9060404.6033403.5539 405.5931

N-(2-Hydroxyethyl)-2-(4-amino-3,5-dichlorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15g):20150306_08-Q5-03 #1-31 RT: 0.00-0.24 AV: 31 NL: 2.24E6T: FTMS + c ESI Full ms [383.00-433.00]

408.0 408.5 409.0 409.5 410.0 410.5 411.0 411.5 412.0 412.5 413.0 413.5 414.0m/z

0

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10

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95

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Relat

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408.0504

410.0472

409.0536

411.0503412.0440

413.0471 413.2649408.3076 409.1820 412.3254 414.2681412.5217408.7866 414.0219411.1534410.8519410.3880407.7125 411.9031409.4502410.1854409.7991


N-Benzyl-2-(4-amino-3,5-dichlorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxamide (15i):20150306_08-Q5-05 #1-30 RT: 0.00-0.24 AV: 30 NL: 4.85E6T: FTMS + c ESI Full ms [429.00-479.00]

453.5 454.0 454.5 455.0 455.5 456.0 456.5 457.0 457.5 458.0 458.5 459.0 459.5 460.0 460.5 461.0 461.5m/z

0

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65

70

75

80

85

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95

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Rela

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454.0710

456.0677

455.0739

457.0705

458.0644

459.0673453.7849 459.5400458.5418 460.0706454.8973 457.1733 460.5381 461.0401456.8157453.3312 461.3926457.8874456.3354455.6656

458.2728

454.5694455.4263


Methyl 2-phenyl-3-hydroxyquinoline-4(1H)-one-5-carboxylate (16a)20150306_02-Q5-Me #1-30 RT: 0.01-0.29 AV: 30 NL: 1.02E7T: FTMS + c ESI Full ms [271.00-321.00]

295.0 295.5 296.0 296.5 297.0 297.5 298.0 298.5 299.0 299.5 300.0 300.5 301.0 301.5 302.0m/z

0

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Rela

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296.0916

297.0946

298.0977 299.0512 302.0116299.5529294.9204 297.5494296.8809 300.8665 301.1402300.5630300.0544295.7575295.4974 296.4273 298.5475

297.2640

Methyl 2-(4-amino-3,5-dichlorophenyl)-3-hydroxyquinoline-4(1H)-one-5-carboxylate (16b)20150306_08-Q5-ME #1-30 RT: 0.01-0.24 AV: 30 NL: 3.94E6T: FTMS + c ESI Full ms [354.00-404.00]

378.0 378.5 379.0 379.5 380.0 380.5 381.0 381.5 382.0 382.5 383.0 383.5 384.0 384.5 385.0 385.5 386.0 386.5m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

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95

100

Rel

ativ

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nce

379.0240

381.0206

380.0270

382.0235383.0172

384.0203383.1545 384.9435 386.9111382.9819379.1603 381.9836378.8811377.9433 385.2905382.4850 385.9466384.4816380.1638379.7840 381.5097380.5312

Crystallography data

Table 1: Experimental data

Crystal data

Chemical formula C19H18N2O3·C3H6O

Mr 380.43

Crystal system, space group

Monoclinic, P21/c

Temperature (K) 298 (1)

a, b, c (Å) 12.5280 (3), 10.6895 (2), 15.9537 (4)

(°) 104.877 (3)

V (Å3) 2064.87 (9)

Z 4

Radiation type Mo K

(mm-1) 0.09

Crystal size (mm) 0.22 × 0.13 × 0.05

Data collection

Diffractometer SuperNova diffractometer (Agilent Technologies) with Atlas detector

Absorption correction Multi-scan CrysAlis PRO, Agilent Technologies, Version 1.171.37.35 Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.

Tmin, Tmax 0.583, 1.000

No. of measured, independent and observed [I > 2(I)] reflections

31019, 3914, 3154

Rint 0.028

(sin /)max (Å-1) 0.610

Refinement

R[F2 > 2(F2)], wR(F2), S

0.067, 0.204, 1.06

No. of reflections 3914

No. of parameters 275

No. of restraints 6

H-atom treatment H-atom parameters constrained

max, min (e Å-3) 0.53, -0.35

Computer programs: CrysAlis PRO, Agilent Technologies, Version 1.171.37.35, SHELXS2013 (Sheldrick, 2014), SHELXL2014/6 (Sheldrick, 2014).

Table 2. Geometric parameters (Å, °).

O1—C3 1.354 (3) C13—C14 1.394 (5)

O1—H1 0.8200 C13—H13 0.9300O2—C4 1.249 (3) C14—H14 0.9300O3—C15 1.227 (3) C16A—C17A 1.486 (9)N2—C16B 1.26 (2) C16A—H16A 0.9700N2—C15 1.322 (3) C16A—H16B 0.9700N2—C16A 1.512 (6) C17A—C18A 1.444 (11)N2—H2 0.8600 C17A—H17A 0.9700N1—C8A 1.361 (3) C17A—H17B 0.9700N1—C2 1.364 (3) C18A—H18A 0.9600N1—H1A 0.8600 C18A—H18B 0.9600C2—C3 1.369 (3) C18A—H18C 0.9600C2—C9 1.482 (3) C16B—C17B 1.46 (4)C3—C4 1.424 (3) C16B—H16C 0.9700C4—C4A 1.445 (3) C16B—H16D 0.9700C4A—C8A 1.410 (3) C17B—C18B 1.24 (4)C4A—C5 1.418 (3) C17B—H17C 0.9700C5—C6 1.369 (4) C17B—H17D 0.9700C5—C15 1.497 (3) C18B—H18D 0.9600C6—C7 1.395 (4) C18B—H18E 0.9600C6—H6 0.9300 C18B—H18F 0.9600C7—C8 1.359 (4) C31—C88B 1.513 (15)C7—H7 0.9300 C31—C88A 1.5198 (5)C8—C8A 1.399 (3) C31—H31A 0.9600C8—H8 0.9300 C31—H31B 0.9600C9—C14 1.379 (4) C31—H31C 0.9600C9—C10 1.380 (4) C30—C88A 1.5199 (5)C10—C11 1.380 (4) C30—C88B 1.5200 (4)C10—H10 0.9300 C30—H30A 0.9600C11—C12 1.350 (6) C30—H30B 0.9600C11—H11 0.9300 C30—H30C 0.9600C12—C13 1.370 (6) C88A—O77A 1.2131 (5)C12—H12 0.9300 C88B—O77B 1.2132 (5)

C2—N1—C8A 122.8 (2) N1—C8A—C4A 119.9 (2) C3—O1—H1 109.00 N1—C8A—C8 119.5 (2)C15—N2—C16B 126.7 (10) C2—C9—C14 121.1 (3)C15—N2—C16A 119.4 (3) C10—C9—C14 118.7 (3)C8A—N1—H1A 119.00 C2—C9—C10 120.2 (3) C2—N1—H1A 119.00 C9—C10—C11 121.0 (3) N1—C2—C9 117.0 (2) C10—C11—C12 120.3 (4) N1—C2—C3 119.1 (2) C11—C12—C13 119.9 (4) C3—C2—C9 124.0 (2) C12—C13—C14 120.6 (4) C16B—N2—H2 110.00 C9—C14—C13 119.5 (3) C15—N2—H2 120.00 N2—C15—C5 115.6 (2) C16A—N2—H2 120.00 O3—C15—N2 122.1 (2) O1—C3—C4 118.5 (2) O3—C15—C5 122.3 (2) O1—C3—C2 119.0 (2) N2—C16A—C17A 113.2 (5) C2—C3—C4 122.5 (2) N2—C16B—C17B 113.7 (18) O2—C4—C3 120.3 (2) C16A—C17A—C18A 117.8 (6) O2—C4—C4A 123.4 (2) C16B—C17B—C18B 117 (3) C3—C4—C4A 116.3 (2) C5—C6—H6 120.00 C4—C4A—C8A 119.3 (2) C7—C6—H6 120.00 C5—C4A—C8A 118.0 (2) C6—C7—H7 120.00 C4—C4A—C5 122.6 (2) C8—C7—H7 120.00 C4A—C5—C15 121.7 (2) C7—C8—H8 120.00 C4A—C5—C6 120.1 (2) C8A—C8—H8 120.00

C6—C5—C15 118.3 (2) C9—C10—H10 119.00 C5—C6—C7 120.7 (3) C11—C10—H10 120.00 C6—C7—C8 120.7 (3) C10—C11—H11 120.00 C7—C8—C8A 119.8 (3) C12—C11—H11 120.00 C4A—C8A—C8 120.7 (2) C11—C12—H12 120.00C13—C12—H12 120.00 H18A—C18A—H18B 109.00 C12—C13—H13 120.00 H18A—C18A—H18C 110.00 C14—C13—H13 120.00 C17A—C18A—H18A 109.00 C9—C14—H14 120.00 C17B—C18B—H18D 110.00 C13—C14—H14 120.00 C17B—C18B—H18E 109.00 N2—C16A—H16A 109.00 C17B—C18B—H18F 110.00 N2—C16A—H16B 109.00 H18D—C18B—H18E 109.00 C17A—C16A—H16A 109.00 H18D—C18B—H18F 110.00 C17A—C16A—H16B 109.00 H18E—C18B—H18F 109.00 H16A—C16A—H16B 108.00 O77A—C88A—C30 141.3 (8) H16C—C16B—H16D 108.00 O77A—C88A—C31 108.7 (7) N2—C16B—H16C 109.00 C30—C88A—C31 108.3 (6) N2—C16B—H16D 109.00 O77B—C88B—C30 93.3 (10) C17B—C16B—H16C 109.00 O77B—C88B—C31 156.1 (12) C17B—C16B—H16D 109.00 C30—C88B—C31 108.6 (10) C18A—C17A—H17A 108.00 C88A—C30—H30A 110.00 C18A—C17A—H17B 108.00 C88A—C30—H30B 109.00 C16A—C17A—H17B 108.00 C88A—C30—H30C 110.00 C16A—C17A—H17A 108.00 C88B—C30—H30A 106.00 H17A—C17A—H17B 107.00 C88B—C30—H30B 100.00 C16B—C17B—H17C 108.00 C88B—C30—H30C 122.00 C16B—C17B—H17D 108.00 H30A—C30—H30B 109.00 H17C—C17B—H17D 107.00 H30A—C30—H30C 109.00 C18B—C17B—H17D 109.00 H30B—C30—H30C 109.00 C18B—C17B—H17C 108.00 C88A—C31—H31A 109.00 C17A—C18A—H18C 109.00 C88A—C31—H31B 109.00 C17A—C18A—H18B 109.00 C88A—C31—H31C 109.00 C88B—C31—H31B 102.00 H31A—C31—H31C 110.00 C88B—C31—H31C 104.00 H31B—C31—H31C 109.00 H31A—C31—H31B 109.00

C8A—N1—C2—C3 3.2 (3) C8A—C4A—C5—C15 178.0 (2)C8A—N1—C2—C9 -177.0 (2) C4—C4A—C8A—N1 1.0 (3)C2—N1—C8A—C4A -3.9 (3) C4—C4A—C8A—C8 -178.1 (2)C2—N1—C8A—C8 175.2 (2) C5—C4A—C8A—N1 180.0 (2)C16A—N2—C15—O3 -16.4 (5) C5—C4A—C8A—C8 0.9 (3)C16A—N2—C15—C5 167.2 (4) C4A—C5—C6—C7 1.2 (4)C15—N2—C16A—C17A

-173.0 (5) C15—C5—C6—C7 -178.5 (3)

N1—C2—C3—O1 178.8 (2) C4A—C5—C15—O3 101.1 (3)N1—C2—C3—C4 0.5 (3) C4A—C5—C15—N2 -82.5 (3)C9—C2—C3—O1 -0.9 (4) C6—C5—C15—O3 -79.3 (3)C9—C2—C3—C4 -179.2 (2) C6—C5—C15—N2 97.2 (3)N1—C2—C9—C10 131.9 (3) C5—C6—C7—C8 0.2 (5)N1—C2—C9—C14 -47.3 (4) C6—C7—C8—C8A -1.0 (5)C3—C2—C9—C10 -48.3 (4) C7—C8—C8A—N1 -178.6 (3)C3—C2—C9—C14 132.5 (3) C7—C8—C8A—C4A 0.5 (4)O1—C3—C4—O2 0.0 (3) C2—C9—C10—C11 179.7 (3)O1—C3—C4—C4A 178.5 (2) C14—C9—C10—C11 -1.0 (5)C2—C3—C4—O2 178.3 (2) C2—C9—C14—C13 -179.2 (3)C2—C3—C4—C4A -3.2 (3) C10—C9—C14—C13 1.5 (5)

O2—C4—C4A—C5 1.9 (3) C9—C10—C11—C12 -0.1 (6)O2—C4—C4A—C8A -179.2 (2) C10—C11—C12—C13 0.7 (7)C3—C4—C4A—C5 -176.5 (2) C11—C12—C13—C14 -0.2 (7)C3—C4—C4A—C8A 2.4 (3) C12—C13—C14—C9 -1.0 (6)C4—C4A—C5—C6 177.3 (2) N2—C16A—C17A—

C18A -70.4 (8)

C4—C4A—C5—C15 -3.0 (3) C8A—C4A—C5—C15 178.0 (2)C8A—C4A—C5—C6 -1.7 (3) C4—C4A—C8A—N1 1.0 (3)

Table 3. Hydrogen bond geometric parameters (Å, °).

D-H···A d(D-H) d(H..A) d(D..A) <DHA O1-H1···O2 0.8200 2.2700 2.701 (3) 113.00 O1-H1···O2i 0.8200 1.9900 2.729 (3) 151.00 N1-H1A···O3ii 0.8600 1.9500 2.798 (3) 170.00 N2-H2···O77Aiii 0.8600 2.0400 2.894 (7) 172.00 C8-H8···O2ii 0.9300 2.4200 3.244 (3) 148.00

i: -x, -y, -z+1ii: -x, y+1/2, -z+3/2iii: -x, -y+1, -z+1

Fluorescent microscope images of compound 14b

Fluorescent microscope images of compound 15i

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