Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CS[C:3]1[N:8]=[C:7]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([C:18]([F:21])([F:20])[F:19])[CH:16]=3)[N:11]([S:22]([C:25]3[CH:31]=[CH:30][C:28]([CH3:29])=[CH:27][CH:26]=3)(=[O:24])=[O:23])[CH:10]=2)[C:6]([C:32]#[N:33])=[CH:5][N:4]=1.ClC1C=CC=C(C(OO)=O)C=1.[F:45][C:46]1[C:51]([OH:52])=[C:50]([F:53])[C:49]([F:54])=[C:48]([F:55])[C:47]=1[F:56]>ClCCl>[F:45][C:46]1[C:47]([F:56])=[C:48]([F:55])[C:49]([F:54])=[C:50]([F:53])[C:51]=1[O:52][C:3]1[N:8]=[C:7]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([C:18]([F:19])([F:20])[F:21])[CH:16]=3)[N:11]([S:22]([C:25]3[CH:26]=[CH:27][C:28]([CH3:29])=[CH:30][CH:31]=3)(=[O:24])=[O:23])[CH:10]=2)[C:6]([C:32]#[N:33])=[CH:5][N:4]=1
Reactant: Oc1c(F)c(F)c(F)c(F)c1F
Reactant: CSc1ncc(C#N)c(-c2cn(S(=O)(=O)c3ccc(C)cc3)c3ncc(C(F)(F)F)cc23)n1
Agent: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)n2cc(-c3nc(Oc4c(F)c(F)c(F)c(F)c4F)ncc3C#N)c3cc(C(F)(F)F)cnc32)cc1
Reaction time: 0.08 h
Yield: 30.9 %

Procedure:
2-(Methylthio)-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile (150 mg, 0.31 mmol) was dissolved in dichloromethane at room temperature. Meta-chloroperbenzoic acid (110 mg, 0.64 mmol) was added in one portion and the reaction was stirred for 5 minutes. Pentafluorophenol (285 mg, 1.55 mmol) was added and the solution was stirred at room temperature for 3 hours. The crude mixture was washed with a diluted solution of sodium bicarbonate and brine. The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography to afford the title compound as a solid (60 mg, 31% yield).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH2:11][CH2:12][S:13]([CH3:16])(=[O:15])=[O:14])=[C:6]([N+:17]([O-])=O)[CH:5]=1.[CH3:21]O>[Pd]>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[CH:8][C:7]2[N:10]([CH2:11][CH2:12][S:13]([CH3:16])(=[O:15])=[O:14])[CH:21]=[N:17][C:6]=2[CH:5]=1)=[O:20]
Reactant: COC(=O)c1ccc(NCCS(C)(=O)=O)c([N+](=O)[O-])c1
Reactant: CO
Agent: [Pd]
Product: COC(=O)c1ccc2c(c1)ncn2CCS(C)(=O)=O
Reaction time: 2 h

Procedure:
4-(2-Methanesulfonyl-ethylamino)-3-nitro-benzoic acid methyl ester (1.63 g, 5.40 mmol) was dissolved in methanol, and 10% Pd/C (150 mg) was added to it under N2 atmosphere. The reaction mixture was then hydrogenated at 1 atmospheric pressure at room temp for 2 h. It was filtered through celite and the filtrate concentrated to yield the desired product. The crude material (1.32 g, 4.85 mmol) was taken in formic acid (10 mL) and allowed to stir at 50° C. for 4 h. The reaction mass was concentrated, diluted with water and extracted with EtOAc. The organic layers were washed with saturated NaHCO3, brine, dried over Na2SO4 and concentrated to give 1-(2-methanesulfonylethyl)-1H-benzoimidazole-5-carboxylic acid methyl ester (77%). 1H NMR (300 MHz, DMSO-d6).
Reaction SMILES: [CH2:1]([N:3]([CH2:27][CH3:28])[C:4](=[O:26])[C:5]1[CH:10]=[CH:9][C:8]([C:11](=[C:18]2[CH2:24][CH:23]3[NH:25][CH:20]([CH2:21][CH2:22]3)[CH2:19]2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:7][CH:6]=1)[CH3:2].[CH:29](=O)[CH2:30][CH3:31].CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+].[Cl:53]CCCl>C(Cl)Cl.CCOCC>[ClH:53].[CH2:27]([N:3]([CH2:1][CH3:2])[C:4](=[O:26])[C:5]1[CH:6]=[CH:7][C:8]([C:11](=[C:18]2[CH2:24][CH:23]3[N:25]([CH2:29][CH2:30][CH3:31])[CH:20]([CH2:21][CH2:22]3)[CH2:19]2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:9][CH:10]=1)[CH3:28]
Reactant: CCC=O
Reactant: CCN(CC)C(=O)c1ccc(C(=C2CC3CCC(C2)N3)c2ccccc2)cc1
Reactant: ClCCCl
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Solvent: ClCCl
Solvent: CC(=O)O
Product: CCCN1C2CCC1CC(=C(c1ccccc1)c1ccc(C(=O)N(CC)CC)cc1)C2
Product: Cl
Reaction time: 16 h

Procedure:
A slurry of 0.4 g (1.0 mmol) N,N-diethyl-4-[(8-azabicyclo[3.2.1]oct-3-ylidene)phenylmethyl]benzamide, 0.11 mL (1.5 mmol) propionaldehyde, 0.1 mL (1.7 mmol) HOAc, and 0.5 g (2.3 mmol) NaBH(OAc)3 in 20 mL DCE was allowed to stir for 16 h. The reaction was made strongly basic with 3N NaOH and diluted with CH2Cl2. The organic layer was separated, washed with brine, dried over K2CO3, filtered, and concentrated. The remaining oil was absorbed onto silica gel and purified by flash chromatography eluted with 5% 0.5 M NH3 in MeOH 95% CH2Cl2. The pure product (0.25 g, 0.6 mmol) was taken up in Et2O, filtered, and precipitated after the addition of ethereal HCl; mp 184-184° C. MS m/z (MH+) 417. 1H NMR 300 MHz (CD3OD) δ 7.2-7.45 (m, 9H), 3.95-4.05 (m, 2H), 3.45-3.6 (m, 2H), 3.2-3.3 (m, 2H), 2.95-3.05 (m, 2H), 2.55-2.7 (m, 4H), 2.2-2.3 (m, 2H), 1.95-2.05 (m, 2H), 1.7-1.85 (m, 2H), 1.0-1.35 (br m, 9H). Anal calc C28H36N2O HCl.0.5H2O: C, 72.78; H, 8.29; N, 6.06. Found: C, 73.01; H, 7.94; N, 5.85.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]([NH:14][C:15](=[O:17])[CH3:16])[CH:11]=[CH:12][CH:13]=2)[CH:5]=[C:4]([C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:20][CH:19]=2)[C:3]=1[C:31]#[N:32].[NH2:33][NH2:34]>CC(O)C>[NH2:32][C:31]1[C:3]2[C:2](=[N:7][C:6]([C:8]3[CH:9]=[C:10]([NH:14][C:15](=[O:17])[CH3:16])[CH:11]=[CH:12][CH:13]=3)=[CH:5][C:4]=2[C:18]2[CH:19]=[CH:20][C:21]([O:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:22][CH:23]=2)[NH:34][N:33]=1
Reactant: NN
Reactant: CC(=O)Nc1cccc(-c2cc(-c3ccc(Oc4ccccc4)cc3)c(C#N)c(Cl)n2)c1
Solvent: CC(C)O
Product: CC(=O)Nc1cccc(-c2cc(-c3ccc(Oc4ccccc4)cc3)c3c(N)n[nH]c3n2)c1
Temperature: 160 °C
Yield: 41 %

Procedure:
A mixture of N-(3-(6-chloro-5-cyano-4-(4-phenoxyphenyl)pyridin-2-yl)phenyl)acetamide (25 mg, 0.057 mmol) and 35% aqueous hydrazine (0.051 mL, 0.568 mmol) in 2-propanol (1.5 mL) was heated to 160° C. under microwave for 1 h then cooled to room temperature. Purification with reverse phase HPLC (Sunfire S10 30×250 mm column), eluting with 60-90% solvent B (10% methanol-90% water-0.1% TFA) in solvent A (90% methanol-10% water-0.1% TFA), gave Example 25 as the faster eluting peak (18 mg, 41% yield, yellow solid) and Example 24 as the slower eluting peak (3 mg, 8% yield, yellow solid).
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][CH:4]=1.[Br:11][C:12]1[CH:13]=[CH:14][C:15]([OH:21])=[C:16]([CH:20]=1)[C:17]([OH:19])=[O:18].[C:22](=[O:25])([O-])[O-].[K+].[K+]>CC(C)=O>[Br:11][C:12]1[CH:13]=[CH:14][C:15]([O:21][CH2:2][C:3]2[CH:8]=[CH:7][C:6]([O:25][CH3:22])=[CH:5][CH:4]=2)=[C:16]([CH:20]=1)[C:17]([O:19][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][CH:4]=1)=[O:18]
Reactant: O=C([O-])[O-]
Reactant: O=C(O)c1cc(Br)ccc1O
Reactant: COc1ccc(CBr)cc1
Agent: [K+]
Solvent: CC(C)=O
Product: COc1ccc(COC(=O)c2cc(Br)ccc2OCc2ccc(OC)cc2)cc1
Temperature: 55 °C
Reaction time: 16 h

Procedure:
1-(Bromomethyl)-4-methoxybenzene (510 mg, 2.53 mmol) was added in a single charge to a stirred suspension of 5-bromo-2-hydroxybenzoic acid (250 mg, 1.15 mmol) and potassium carbonate (318 mg, 2.30 mmol) in acetone (40 ml) over 1 min under nitrogen. The reaction mixture was stirred at 55° C. for 16 h. The organic phase was evaporated and the residue was washed with water (25 ml), extracted with ethyl acetate (3×30 ml) and evaporated in vacuo to yield the title compound as a light yellow solid. 400 mg.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]Cl)=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.[Cl:17][C:18]1[CH:32]=[C:31]([O:33][C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[CH:35]=2)[CH:30]=[CH:29][C:19]=1[O:20][CH2:21][CH2:22][O:23][C:24]([NH:26][CH2:27][CH3:28])=[O:25].N1C=CC=CC=1>CCOCC>[Cl:17][C:18]1[CH:32]=[C:31]([O:33][C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[CH:35]=2)[CH:30]=[CH:29][C:19]=1[O:20][CH2:21][CH2:22][O:23][C:24]([N:26]([CH2:27][CH3:28])[S:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)=[O:25]
Reactant: ClSc1ccc(Cl)cc1
Reactant: CCNC(=O)OCCOc1ccc(Oc2cccc(Cl)c2)cc1Cl
Solvent: c1ccncc1
Solvent: CCOCC
Solvent: Cc1ccccc1
Product: CCN(Sc1ccc(Cl)cc1)C(=O)OCCOc1ccc(Oc2cccc(Cl)c2)cc1Cl
Reaction time: 16 h

Procedure:
A solution of 2 g of 4-chlorophenylsulfenyl chloride in 1 0 ml of toluene is added dropwise with stirring at 0°-5° C. in the course of approximately 30 minutes to a mixture of 3.7 g of 1-[2-chloro-4-(3-chlorophenoxy)phenoxy]2-ethylaminocarbonyloxyethane, 10 ml of pyridine and 10 ml of toluene, and stirring is continued for 16 hours at room temperature. The reaction mixture is diluted with 100 ml of ether, washed three times using ice-cold 1N hydrochloric acid and three times using water, the organic phase is dried over sodium sulfate and the solvent is evaporated in vacuo. The crude product is purified on silica gel using diethyl ether/n-hexane (1:3) as mobile phase. This gives the title compound of refractive index nD20 1.6209.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:11]=1[NH:10][CH:9]=[CH:8]2.[H-].[Na+].Br[CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1>CN(C)C=O>[CH:16]1([CH2:15][N:10]2[C:11]3[C:7](=[CH:6][CH:5]=[CH:4][C:3]=3[O:2][CH3:1])[CH:8]=[CH:9]2)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1
Reactant: COc1cccc2cc[nH]c12
Reactant: BrCC1CCCCC1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1cccc2ccn(CC3CCCCC3)c12
Temperature: 25 °C
Reaction time: 42 h
Yield: 90.3 %

Procedure:
To a solution of 7-methoxyindole (5.00 g, 34.0 mmol) in dimethylformamide (50 ml) under nitrogen was added sodium hydride (60% dispersion in mineral oil; 1.50 g, 37.4 mmol). The mixture was stirred at room temperature for 10 minutes before the addition of bromomethylcyclohexane (5.20 ml, 37.4 mmol). The resulting mixture was stirred at room temperature for 42 hours and then partitioned between ethyl acetate (150 ml) and water (150 ml). The aqueous layer was extracted with ethyl acetate (150 ml) and the combined organic layers were washed with brine (150 ml), dried over sodium sulfate and concentrated in vacuo. The crude intermediate was purified by flash column chromatography eluting with 0-10% (v/v) ethyl acetate in n-heptane to afford 1-(cyclohexyl)methyl-7-methoxy-1H-indole (7.48 g, 30.7 mmol). Chloroacetyl chloride (8.66 ml, 109 mmol) was added dropwise over a period of 1.5 h, to a stirred solution of pyridine (2.20 ml, 27.2 mmol) and 1-(cyclohexyl)methyl-7-methoxy-1H-indole (6.60 g, 27.2 mmol) in toluene (50 ml) at 55° C. The resulting mixture was heated at 55° C. for a further 0.5 h then allowed to cool to room temperature. Water (60 ml) and methanol (10 ml) were added. The organic layer was separated and concentrated under reduced pressure to afford a dark brown residue. The residue was purified by column chromatography eluting with 5% (v/v) ethyl acetate in n-heptane. The solid obtained was repeatedly recrystallised from ether to give 2-chloro-1-[1-(cyclohexyl)methyl-7-methoxy-1H-indol-3-yl]ethanone as a white solid (1.40 g).
Reaction SMILES: [NH:1]1[CH2:10][CH2:9][CH2:8][C:7]2[N:6]=[CH:5][C:4]3[CH:11]=[CH:12][CH:13]=[CH:14][C:3]=3[C:2]1=2.[Br:15][CH:16]([CH3:20])[C:17](Br)=[O:18]>C(OCC)C>[BrH:15].[Br:15][CH:16]([CH3:20])[C:17]([N:1]1[CH2:10][CH2:9][CH2:8][C:7]2[N:6]=[CH:5][C:4]3[CH:11]=[CH:12][CH:13]=[CH:14][C:3]=3[C:2]1=2)=[O:18]
Reactant: c1ccc2c3c(ncc2c1)CCCN3
Reactant: CC(Br)C(=O)Br
Solvent: CCOCC
Product: Br
Product: CC(Br)C(=O)N1CCCc2ncc3ccccc3c21
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A solution of 15.0 g of 1,2,3,4-tetrahydrobenzo[c]-1,5-naphthyridine in 24 ml of 2-bromopropionyl bromide was stirred overnight at ambient temperature. The solution was then diluted with anhydrous diethyl ether and stirred for approximately 3 hours at ambient temperature. A precipitate separated from the solution. The precipitate was collected by vacuum filtration and dried under vacuum at 40° C. overnight. The solid was recrystallized from a mixture of 95% ethanol and anhydrous diethyl ether (1:2) to yield 28.22 g of a powdery solid.
Reaction SMILES: CS([C:4]1[NH:5][CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10])=O.[CH3:12][C:13]1[NH:17][CH:16]=[N:15][C:14]=1[CH2:18][S:19][CH2:20][CH2:21][NH2:22]>CO>[CH3:12][C:13]1[NH:17][CH:16]=[N:15][C:14]=1[CH2:18][S:19][CH2:20][CH2:21][NH:22][C:4]1[NH:5][CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10]
Reactant: CS(=O)c1[nH]ccc1[N+](=O)[O-]
Reactant: Cc1[nH]cnc1CSCCN
Solvent: CO
Product: Cc1[nH]cnc1CSCCNc1[nH]ccc1[N+](=O)[O-]
Yield: 34.1 %

Procedure:
A solution of 2-methylsulphinyl-3-nitropyrrole (2 g, 0.01 mol) and 2-(5-methyl-4-imidazolylmethylthio)-ethylamine (2 g, 0.01 mol) in methanol (50 ml) was refluxed for 7 days and evaporated to dryness. The residue was chromatographed on a silica gel column eluted with ethyl acetate, and the eluate was evaporated to dryness and recrystallised from propan-2-ol to give 2-[2-(5-methyl-4-imidazolylmethylthio)ethylamino]-3-nitropyrrole (0.96 g, 31%) m.p. 161°-162°.
Reaction SMILES: C(Cl)(=O)C.[NH:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([N:20]3[CH2:28][C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH2:21]3)=[O:19])=[CH:13][CH:12]=2)[CH2:7][CH2:6]1.NC1C=C2C(=CC=1)CN(C(NC1C=[CH:46][C:45]([C:48](=[O:53])NCCC)=[CH:44]C=1)=O)C2>>[C:48]([N:5]1[CH2:6][CH2:7][CH:8]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([N:20]3[CH2:28][C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH2:21]3)=[O:19])=[CH:13][CH:12]=2)[CH2:9][CH2:10]1)(=[O:53])[CH:45]([CH3:46])[CH3:44]
Reactant: O=C(Nc1ccc(C2CCNCC2)cc1)N1Cc2ccccc2C1
Reactant: CCCNC(=O)c1ccc(NC(=O)N2Cc3ccc(N)cc3C2)cc1
Solvent: CC(=O)Cl
Product: CC(C)C(=O)N1CCC(c2ccc(NC(=O)N3Cc4ccccc4C3)cc2)CC1

Procedure:
The title compound was prepared as described in Example 278, substituting isobutyryl chloride for acetyl chloride and N-[4-(piperidin-4-yl)phenyl]-1,3-dihydro-2H-isoindole-2-carboxamide for 5-amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.28 (s, 1H), 7.46-7.48 (m, 2H), 7.34-7.39 (m, 2H), 7.29-7.33 (m, 2H), 7.12-7.14 (m, 2H), 4.75-4.76 (bs, 4H), 4.53-4.58 (m, 1H), 4.03-4.07 (m, 1H), 3.06-3.14 (m, 1H), 2.86-2.93 (m, 1H), 2.67-2.74 (m, 1H), 2.53-2.61 (m, 1H), 1.75-1.84 (m, 2H), 1.45-1.56 (m, 1H), 1.33-1.45 (m, 1H), 1.03 (d, J=6.7 Hz, 3H), 1.00 (d, J=6.6 Hz, 3H); MS (ESI(−)) m/e 390 (M−H)−.
Reaction SMILES: [NH2:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([F:14])([F:13])[F:12])[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[C:4]2[CH:19]=[CH:20][CH:21]=[CH:22][C:3]1=2.[C:23](O)(=[O:27])[C@H:24]([CH3:26])[OH:25].O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C.Cl.CN(C)CCCN=C=NCC>O1CCCC1>[OH:25][C@@H:24]([CH3:26])[C:23]([NH:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([F:14])([F:12])[F:13])[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[C:4]2[CH:19]=[CH:20][CH:21]=[CH:22][C:3]1=2)=[O:27]
Reactant: N[C@@H]1C(=O)N(CC(F)(F)F)c2ccccc2-c2ccccc21
Reactant: C[C@H](O)C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: C[C@H](O)C(=O)N[C@@H]1C(=O)N(CC(F)(F)F)c2ccccc2-c2ccccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 68.4 %

Procedure:
A solution of 0.26 g (0.85 mmol) (S)-7-amino-5-(2,2,2-trifluoro-ethyl)-5H,7H-dibenzo[b,d]azepin-6-one in 18 ml tetrahydrofurane was treated at 0° C. with 0.08 g (0.94 mmol) L-lactic acid, 0.13 g (0.85 mmol) 1-hydroxybenzotriazole hydrate, 297 μl (1.70 mmol) N-ethyldiisopropylamine and 0.17 g (0.85 mmol) N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimid-hydrochlorid. After stirring at room temperature overnight the mixture was extracted with 1N aqueous hydrochloric acid/ethylacetate. Purification by chromatography on silicagel with ethylacetate/heptane (0-100/100-0) yielded 0.22 g (68%) (S)-2-hydroxy-N—[(S)-6-oxo-5-(2,2,2-trifluoro-ethyl)-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-propionamide as grey solid, MS: m/e: 379.4 (M+H+), [α] 589=−23° (1.1% in CHCl3).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:24])[CH2:4][C:5]1[CH:10]=[C:9]([Cl:11])[CH:8]=[C:7]([O:12][C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-])=O)=[CH:15][C:14]=2[CH2:22]Br)[CH:6]=1.[CH3:25][CH:26]([SH:28])[CH3:27].[C:29](Cl)(=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31]>>[CH3:1][O:2][C:3](=[O:24])[CH2:4][C:5]1[CH:6]=[C:7]([O:12][C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:29](=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:15][C:14]=2[CH2:22][S:28][CH:26]([CH3:27])[CH3:25])[CH:8]=[C:9]([Cl:11])[CH:10]=1
Reactant: COC(=O)Cc1cc(Cl)cc(Oc2ccc([N+](=O)[O-])cc2CBr)c1
Reactant: CC(C)(C)C(=O)Cl
Reactant: CC(C)S
Product: COC(=O)Cc1cc(Cl)cc(Oc2ccc(NC(=O)C(C)(C)C)cc2CSC(C)C)c1

Procedure:
Following the procedures described in Example 21, Step 8 (starting from [3-(2-bromomethyl-4-nitro-phenoxy)-5-chloro-phenyl]-acetic acid methyl ester and 2-propanethiol), Example 21, Step 9, and Example 21, Step 10 (using pivaloyl chloride), {3-Chloro-5-[4-(2,2-dimethyl-propionylamino)-2-isopropylsulfanylmethyl-phenoxy]-phenyl}-acetic acid methyl ester was obtained. Hydrolysis of the ester according to the procedure described in Example 21, Step 11 provided the acid.
Reaction SMILES: [C:1]1([P:7]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[O:8]C2C=CC=CC=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:22](=O)[CH3:23].[N:25]1([S:31]([NH2:34])(=[O:33])=[O:32])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1>ClC1C=CC=CC=1>[C:16]1([O:15][P:7]([CH:22]([NH:34][S:31]([N:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)(=[O:33])=[O:32])[CH3:23])([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[O:8])[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: c1ccc(OP(Oc2ccccc2)c2ccccc2)cc1
Reactant: CC=O
Reactant: NS(=O)(=O)N1CCCCC1
Solvent: Clc1ccccc1
Product: CC(NS(=O)(=O)N1CCCCC1)P(=O)(Oc1ccccc1)c1ccccc1
Yield: 75 %

Procedure:
This compound is obtained in 75% yield in a crude form from a mixture of equimolar quantities of diphenyl phenylphosphonite, acetaldehyde, and piperidinosulfonylamine in chlorobenzene. Recrystallization of a portion twice from acetonitrile gives a white solid product: mp 152°-165°; 31P nmr(DMSO-d6) -38.4 ppm.
Reaction SMILES: [F:1][C:2]1[C:11]([F:12])=[C:10]2[C:5]([CH:6]=[C:7]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[C:15]=3[C:21](=[O:23])[CH3:22])[CH:8]=[N:9]2)=[CH:4][CH:3]=1.[CH3:24][Mg]Cl.Cl>O1CCCC1>[F:1][C:2]1[C:11]([F:12])=[C:10]2[C:5]([CH:6]=[C:7]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[C:15]=3[C:21]([OH:23])([CH3:24])[CH3:22])[CH:8]=[N:9]2)=[CH:4][CH:3]=1
Reactant: C[Mg]Cl
Reactant: CC(=O)c1c(F)cccc1Oc1cnc2c(F)c(F)ccc2c1
Agent: Cl
Solvent: C1CCOC1
Product: CC(C)(O)c1c(F)cccc1Oc1cnc2c(F)c(F)ccc2c1
Temperature: 0 °C

Procedure:
After 0.64 g of 1-[2-(7,8-difluoroquinolin-3-yloxy)-6-fluoro-phenyl]-ethanone was dissolved in 10 ml of tetrahydrofuran, the resultant was cooled to 0° C. and 1.5 ml of methylmagnesium chloride (3.0 M tetrahydrofuran solution) was added dropwise. Dilute hydrochloric acid was added to the reaction solution, and the liquid was separated with ethyl acetate. The organic layer was concentrated and purified by silica gel column chromatography to obtain 0.49 g of 2-[2-(7,8-difluoroquinolin-3-yloxy)-6-fluoro-phenyl]-propan-2-ol (Compound Number 124).
Reaction SMILES: [OH:1][C:2]1[CH:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH2:5][C:4](=[O:13])[CH:3]=1.[CH:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[CH2:22]([C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][CH:28]=[C:27]2[CH2:33][CH2:34][NH2:35])C>>[NH2:35][CH2:34][CH2:33][C:27]1[C:26]2[C:30](=[CH:31][CH:32]=[C:24]([CH3:22])[CH:25]=2)[NH:29][C:28]=1[CH:14]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:3]1[C:4](=[O:13])[CH2:5][CH:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:2]=1[OH:1]
Reactant: O=C1C=C(O)C(c2ccccc2)C1
Reactant: CCc1ccc2[nH]cc(CCN)c2c1
Reactant: O=Cc1ccccc1
Product: Cc1ccc2[nH]c(C(C3=C(O)C(c4ccccc4)CC3=O)c3ccccc3)c(CCN)c2c1

Procedure:
Using general procedure C, 3-hydroxy-4-phenyl-cyclopent-2-enone (Lit. 17) was reacted with benzaldehyde and 2-(5-ethyl-1H-indol-3-yl)-ethylamine to give the title compound as orange solid. MS: 437.1 ([M+H]+).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]([N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:15])[CH:11]=[C:10]([C:21](O)=[O:22])[CH:9]=2)=[CH:4][CH:3]=1.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.[CH3:47][C:48]1[N:53]=[CH:52][C:51]([CH2:54][NH2:55])=[CH:50][CH:49]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]([N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:15])[CH:11]=[C:10]([C:21]([NH:55][CH2:54][C:51]3[CH:52]=[N:53][C:48]([CH3:47])=[CH:49][CH:50]=3)=[O:22])[CH:9]=2)=[CH:4][CH:3]=1
Reactant: Cc1ccc(CN)cn1
Reactant: O=C(O)c1cc(C(=O)N2CCCC2)cc(-c2ccc(Br)cc2)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: ClCCl
Product: Cc1ccc(CNC(=O)c2cc(C(=O)N3CCCC3)cc(-c3ccc(Br)cc3)c2)cn1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a mixture of 4′-bromo-5-(pyrrolidine-1-carbonyl)-biphenyl-3-carboxylic acid (1.65 g, 4.41 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.7 g, 8.8 mmol), 1-hydroxybenzotriazole hydrate (0.20 g, 1.3 mmol), and CH2Cl2 (50 mL) were added (6-methylpyridin-3-yl)methanamine (0.81 g, 6.6 mmol) and N,N-diisopropylethylamine (1.5 mL, 8.8 mmol). The mixture was stirred at room temperature overnight and then washed with water, dried (Na2SO4), and concentrated. The residue was purified by silica gel column (0-15% MeOH/CH2Cl2) and analytical sample was purified by preparative HPLC (100×20.2 mm, C18 column; 30-80% CH3CN-water[10 mM Et2NH]) to afford a white foam.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:5]2=[N:6][C:7](=[O:9])[N:8]=[C:4]2[CH:3]=1.[OH:12][C:13]1[C:14]([C:23](O)=[O:24])=[CH:15][C:16]2[C:21]([CH:22]=1)=[CH:20][CH:19]=[CH:18][CH:17]=2>>[OH:12][C:13]1[C:14]([C:23]([NH:1][C:2]2[CH:11]=[CH:10][C:5]3=[N:6][C:7](=[O:9])[N:8]=[C:4]3[CH:3]=2)=[O:24])=[CH:15][C:16]2[C:21]([CH:22]=1)=[CH:20][CH:19]=[CH:18][CH:17]=2
Reactant: Nc1ccc2c(c1)=NC(=O)N=2
Reactant: O=C(O)c1cc2ccccc2cc1O
Product: O=C1N=c2ccc(NC(=O)c3cc4ccccc4cc3O)cc2=N1

Procedure:
The product thus obtained is fit for the preparation of azo pigments of high fastness and according to HPLC contains <0.1% of 5-aminobenzimidazolone and <0.1% of 3-hydroxy-2-naphthoic acid.
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][CH:5]=1)[CH2:2][CH3:3].[Mg].[CH2:12]([C@H:17]1[CH2:22][CH2:21][C@H:20]([C:23]2[C:24](=O)[CH2:25][CH2:26][CH2:27][CH:28]=2)[CH2:19][CH2:18]1)[CH2:13][CH2:14][CH2:15][CH3:16].Cl.C([O:33]CC)C>>[CH2:12]([C@H:17]1[CH2:22][CH2:21][C@H:20]([C:23]2[CH2:24][CH2:25][C:26]([C:7]3[CH:8]=[CH:9][C:4]([CH2:1][CH2:2][CH3:3])=[CH:5][CH:6]=3)([OH:33])[CH2:27][CH:28]=2)[CH2:19][CH2:18]1)[CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCc1ccc(Br)cc1
Reactant: CCCCC[C@H]1CC[C@H](C2=CCCCC2=O)CC1
Reactant: CCOCC
Agent: Cl
Agent: [Mg]
Product: CCCCC[C@H]1CC[C@H](C2=CCC(O)(c3ccc(CCC)cc3)CC2)CC1

Procedure:
A solution of 6.1 g of 4-propylbromobenzene in 25 ml of anhydrous diethyl ether was added dropwise under stirring at 10°-15° C. to 0.66 g of magnesium metal powder, followed by reaction at room temperature for one hour so that a Grignard reagent was formed. After 5 g of trans-4-pentylcyclohexylcyclohexenone were added under stirring at -10° to 0° C. to the thus-formed Grignard reagent, they were reacted at room temperature for additional 1 hour. After the completion of the reaction, diluted hydrochloric acid was added dropwise to the reaction mixture, followed by the extraction of the reaction mixture with diethyl ether. After the extract was washed with saturated NaCl, anhydrous sodium sulfate was added to dry the extract. The diethyl ether was distilled off under reduced pressure, whereby 1-(trans-4-pentylcyclohexyl)-4-(4-propylphenyl)-4-hydroxycyclohexene was obtained as a crude reaction product.