Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C@H:2]1[C@H:7]([NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:6][CH2:5][C@@H:4]([C:16]([NH2:18])=[O:17])[CH2:3]1.[N+:19]([C:22]1[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=1)([O-:21])=[O:20].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1.CN(C=O)C>[C:12]([O:11][C:9]([NH:8][C@@H:7]1[CH2:6][CH2:5][C@@H:4]([C:16](=[O:17])[NH2:18])[CH2:3][C@@H:2]1[O:1][C:26](=[O:27])[C:25]1[CH:24]=[CH:23][C:22]([N+:19]([O-:21])=[O:20])=[CH:30][CH:29]=1)=[O:10])([CH3:13])([CH3:14])[CH3:15]
Reactant: CC(C)(C)OC(=O)N[C@@H]1CC[C@@H](C(N)=O)C[C@H]1O
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N[C@@H]1CC[C@@H](C(N)=O)C[C@@H]1OC(=O)c1ccc([N+](=O)[O-])cc1
Reaction time: 0.08 h
Yield: 53.7 %

Procedure:
To (1R,3R,4R)-3-hydroxy-4-tert-butoxycarbonylamino-cyclohexanecarboxylic acid amide (e) (2.78 g, 10.8 mmol), para-nitrobenzoic acid (2.16 g, 12.9 mmol) and triphenylphosphine (3.38 g, 12.9 mmol) in dry THF (200 mL) and DMF (25 mL) under argon was added dropwise diisopropyl azodicarboxylate (2.5 mL, 12.9 mmol) at 0° C. After 5 min at 0° C. and 17 hours at room temperature, the mixture was concentrated in vacuo and the residue purified by flash column chromatography (silica gel, DCM/MeOH, 0-4%) to give a white solid (2.36 g, 5.8 mmol, 54%).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[CH2:27][CH2:28][C:29](O)=[O:30])=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[CH3:32][C:33]([NH2:41])([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[CH3:34]>>[CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[CH2:27][CH2:28][C:29](=[O:30])[NH:41][C:33]([CH3:34])([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[CH3:32])=[CH:17][CH:16]=3)=[CH:13][CH:14]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4CCC(=O)O)cc3)cc2)CC1
Reactant: CC(C)(N)c1ccccc1
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4CCC(=O)NC(C)(C)c4ccccc4)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 33, Step 4, using 1-{4′-[4-(2-carboxy-ethyl)-3-methyl-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid ethyl ester and 1-methyl-1-phenyl-ethylamine.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]#[N:11])[CH:5]=[C:6]([Cl:8])[CH:7]=1.Cl.[OH-].[Na+]>C1COCC1.C(OCC)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][NH2:11])[CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: N#CCc1cc(Cl)cc(Cl)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCOCC
Product: NCCc1cc(Cl)cc(Cl)c1
Temperature: 25 °C
Yield: 85.1 %

Procedure:
2-(3,5-dichlorophenyl)acetonitrile (155.5 mg, 0.836 mmol), 0.3 molar in THF, was heated to reflux and then treated with Borane-methyl sulfide complex (87.20 μL, 0.919 mmol). After 1 hour of refluxing, the reaction mixture was cooled to ambient temperature and then treated dropwise with 5.0 molar hydrochloric acid (601.8 μl, 3.009 mmol). The reaction mixture was heated to reflux for an additional 30 minutes. After 30 minutes the reaction mixture was cooled to 0° C. and treated with 1.0 molar sodium hydroxide (4597 μL, 4.597 mmol). The reaction mixture was diluted with diethyl ether and partitioned with deionized water. The organic layer was dried with potassium carbonate 98% powder, filtered, concentrated, and dried for one minute under high vacuum to provide the title compound (135.2 mg, 0.7113 mmol, 85.1% yield) as a light yellow oil.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:6]=[C:7]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[CH:8]=[CH:9][C:10]=1[O:11][CH2:12][CH2:13][C:14]1[N:15]=[C:16]([S:19][C:20]([CH3:29])([CH3:28])[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[S:17][CH:18]=1)=[O:4].[OH-].[Na+]>CO.O1CCCC1>[F:36][C:33]1[CH:34]=[CH:35][C:30]([C:7]2[CH:8]=[CH:9][C:10]([O:11][CH2:12][CH2:13][C:14]3[N:15]=[C:16]([S:19][C:20]([CH3:29])([CH3:28])[C:21]([O:23][C:24]([CH3:27])([CH3:25])[CH3:26])=[O:22])[S:17][CH:18]=3)=[C:5]([C:3]([OH:4])=[O:2])[CH:6]=2)=[CH:31][CH:32]=1
Reactant: COC(=O)c1cc(-c2ccc(F)cc2)ccc1OCCc1csc(SC(C)(C)C(=O)OC(C)(C)C)n1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)C(C)(C)Sc1nc(CCOc2ccc(-c3ccc(F)cc3)cc2C(=O)O)cs1
Temperature: 25 °C
Reaction time: 8 h
Yield: 83.5 %

Procedure:
4-(2-{2-[(2-tert-Butoxy-1,1-dimethyl-2-oxoethyl)thio]-1,3-thiazol-4-yl}ethoxy)-4′-fluoro-biphenyl-3-carboxylic acid methyl ester (1.6 g) synthesized in Example 92-2 was dissolved in methanol (15 mL) and tetrahydrofuran (20 mL), aqueous sodium hydroxide solution (1 mol/L, 15 ml) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, aqueous 10% citric acid solution was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give the title compound (1.3 g) as an oil.
Reaction SMILES: [CH3:1][C:2]1[C:19]([CH3:20])=[CH:18][C:5]2[NH:6][C:7]([C:9]3[C:13]4[CH2:14][NH:15][CH2:16][CH2:17][C:12]=4[NH:11][N:10]=3)=[N:8][C:4]=2[CH:3]=1.[CH2:21]([N:23]([CH2:27][CH3:28])[C:24](Cl)=[O:25])[CH3:22]>>[CH2:21]([N:23]([CH2:27][CH3:28])[C:24]([N:15]1[CH2:16][CH2:17][C:12]2[NH:11][N:10]=[C:9]([C:7]3[NH:6][C:5]4[CH:18]=[C:19]([CH3:20])[C:2]([CH3:1])=[CH:3][C:4]=4[N:8]=3)[C:13]=2[CH2:14]1)=[O:25])[CH3:22]
Reactant: CCN(CC)C(=O)Cl
Reactant: Cc1cc2nc(-c3n[nH]c4c3CNCC4)[nH]c2cc1C
Product: CCN(CC)C(=O)N1CCc2[nH]nc(-c3nc4cc(C)c(C)cc4[nH]3)c2C1

Procedure:
By proceeding in a manner similar to Example 258(f) above, but using 3-(5,6-dimethyl-1H-benzoimidazol-2-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine [Example 251(a)] and diethylcarbamyl chloride, and subjecting the reaction product to flash column chromatography eluting with ethyl acetate to ethyl acetate/methanol (49:1, v/v), there was prepared 3-(5,6-dimethyl-1H-benzoimidazol-2-yl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid diethylamide (20.9 mg) as an off-white solid. LC-MS (METHOD J): RT=3.44 minutes, 367 (M+H)+.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][CH:23]=2)[N:20]=[CH:19][N:18]([CH:24]([C:31]([O:33]C(C)(C)C)=[O:32])[CH2:25][O:26]C(C)(C)C)[C:17]3=[O:38])[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C1(OC)C=CC=CC=1>[OH:26][CH2:25][CH:24]([N:18]1[C:17](=[O:38])[C:16]2[C:21](=[CH:22][CH:23]=[C:14]([N:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)[CH:15]=2)[N:20]=[CH:19]1)[C:31]([OH:33])=[O:32]
Reactant: CC(C)(C)OCC(C(=O)OC(C)(C)C)n1cnc2ccc(N3CCN(C(=O)OC(C)(C)C)CC3)cc2c1=O
Solvent: O=C(O)C(F)(F)F
Solvent: COc1ccccc1
Product: O=C(O)C(CO)n1cnc2ccc(N3CCNCC3)cc2c1=O
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 156.1 %

Procedure:
4-[3-(2-tert-butoxy-1-tert-butoxycarbonyl-ethyl)-4-oxo-3,4-dihydro-quinazolin-6-yl]-piperazine-1-carboxylic acid tert-butyl ester (4.7 g) was dissolved in anisole (8 mL) and cooled in an ice-water bath. Trifluoroacetic acid (80 mL) is added slowly. The mixture was stirred for 5 minutes while cooling with the ice-water bath and then for 5 hours at room temperature; during this time, the color of the reaction mixture changed from orange to red to purple to dark blue over time. At this time, the reaction solvents were removed in vacuo, leaving a blue oil. This oil was triturated with dry diethyl ether and evaporated to dryness again. The residue was again triturated with dry diethyl ether and stirred overnight with this solvent. At this time, the mixture was filtered and the resulting solid was washed with diethyl ether and dried in a vacuum oven, resulting in 4.4 g of a solid. This solid was used in the next step without further purification. H1-NMR spectroscopy indicated a spectrum consistent with 3-hydroxy-2-(4-oxo-6-piperazin-1-yl-4H-quinazolin-3-yl)-propionic acid.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([O:24][CH:25]([CH3:27])[CH3:26])=[C:13]([C:15]2[NH:23][C:18]3=[N:19][CH:20]=[CH:21][CH:22]=[C:17]3[N:16]=2)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC1C=CC=C(C(OO)=[O:36])C=1>C(Cl)(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([O:24][CH:25]([CH3:27])[CH3:26])=[C:13]([C:15]2[NH:23][C:18]3=[N+:19]([O-:36])[CH:20]=[CH:21][CH:22]=[C:17]3[N:16]=2)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)Oc1ccc(OCc2ccccc2)cc1-c1nc2cccnc2[nH]1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClC(Cl)Cl
Product: CC(C)Oc1ccc(OCc2ccccc2)cc1-c1nc2ccc[n+]([O-])c2[nH]1

Procedure:
A solution (10 ml) of 2-[5-(benzyloxy)-2-isopropoxyphenyl]-3H-imidazo[4,5-b]pyridine (0.2 g) and m-chloroperbenzoic acid (0.15 g) in chloroform was stirred at room temperature for 18 hr. The reaction mixture was washed with aqueous sodium hydrogencarbonate solution, dried over magnesium sulfate and concentrated to give the title compound as colorless crystals. purity 80%. M+H: 376.
Reaction SMILES: [Cl:1]C1C=C2C(C(=O)C(C(O)=O)=CN2C2C=CC=C(F)C=2)=CC=1.[F:23][C:24]1[CH:29]=[CH:28][C:27]([N:30]2[C:39]3[C:34](=[CH:35][CH:36]=[C:37](C4C=CN=CC=4)[CH:38]=3)[C:33](=[O:46])[C:32]([C:47]([NH2:49])=[O:48])=[CH:31]2)=[CH:26][CH:25]=1>>[Cl:1][C:37]1[CH:38]=[C:39]2[C:34]([C:33](=[O:46])[C:32]([C:47]([NH2:49])=[O:48])=[CH:31][N:30]2[C:27]2[CH:28]=[CH:29][C:24]([F:23])=[CH:25][CH:26]=2)=[CH:35][CH:36]=1
Reactant: NC(=O)c1cn(-c2ccc(F)cc2)c2cc(-c3ccncc3)ccc2c1=O
Reactant: O=C(O)c1cn(-c2cccc(F)c2)c2cc(Cl)ccc2c1=O
Product: NC(=O)c1cn(-c2ccc(F)cc2)c2cc(Cl)ccc2c1=O

Procedure:
7-Chloro-1,4-dihydro-1-(3-fluorophenyl)-4-oxo-3-quinolinecarboxamide [IV; R=H, R1 =3-FC6H4, R2 =H, R6H, X=Cl]was prepared from 7.36 g 7-chloro-1,4-dihydro1-(3-fluorophenyl)-4-oxo-3-quinolinecarboxylic acid by the procedure of Example 1, part (h), and was obtained (7.14 g) as a colorless solid, m.p. 294-296° C. when recrystallized from DMF. e) 1,4-Dihydro-1-(3-fluorophenyl)-4-oxo-7-(4-pyridinyl)3-quinolinecarboxamide [I; R=H, R1 =3-FC6H4, R2 =H, R6H, R7 4 -pyridinyl]was prepared from 4.13 g 7-chloro-1,4-dihydro-1-(3-fluorophenyl)-4-oxo-3-quinolinecarboxamide, 3.78 g 4-trimethylstannylpyridine and 0.46 g dichloro-bis-triphenylphosphine palladium according to the procedure of Example 37, part (c), and was obtained (2.4 g) in the form of its methanesulfonate salt, m.p. above 320° C. when recrystallized from methanol.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[Cl:22])[CH2:5][C:6]1[C:7](=[O:18])[O:8][C:9]2[C:14]([C:15]=1[CH3:16])=[CH:13][CH:12]=[C:11]([OH:17])[CH:10]=2.[I-].[CH3:24][N:25]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:26](N1C=C[N+](C)=C1)=[O:27]>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[Cl:22])[CH2:5][C:6]1[C:7](=[O:18])[O:8][C:9]2[C:14]([C:15]=1[CH3:16])=[CH:13][CH:12]=[C:11]([O:17][C:26](=[O:27])[N:25]([CH3:24])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH:10]=2
Reactant: CN(C(=O)n1cc[n+](C)c1)c1ccccc1
Reactant: Cc1c(Cc2ccc(Cl)c(Cl)c2)c(=O)oc2cc(O)ccc12
Agent: [I-]
Product: Cc1c(Cc2ccc(Cl)c(Cl)c2)c(=O)oc2cc(OC(=O)N(C)c3ccccc3)ccc12

Procedure:
The title compound was prepared from 3-(3,4-dichloro-benzyl)-7-hydroxy-4-methyl-2H-chromen-2-one and 3-(methyl-phenyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide (white solid). HPLC-MS m/z=468 (M+1), Rt: 5.47 min.
Reaction SMILES: Cl.Cl.[O:3]1[C:8]2=[CH:9][CH:10]=[CH:11][C:7]2=[CH:6][C:5]([CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][N:13]2[CH2:18][CH2:19][C@H:20]2[CH2:25][CH2:24][C@H:23]([NH2:26])[CH2:22][CH2:21]2)=[CH:4]1.[OH:27][C:28]([CH3:33])([CH3:32])[C:29](N)=[O:30]>>[O:3]1[C:8]2=[CH:9][CH:10]=[CH:11][C:7]2=[CH:6][C:5]([CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][N:13]2[CH2:18][CH2:19][C@H:20]2[CH2:21][CH2:22][C@H:23]([NH:26][C:29](=[O:30])[C:28]([OH:27])([CH3:33])[CH3:32])[CH2:24][CH2:25]2)=[CH:4]1
Reactant: N[C@H]1CC[C@H](CCN2CCCCC2c2coc3cccc-3c2)CC1
Reactant: CC(C)(O)C(N)=O
Agent: Cl
Product: CC(C)(O)C(=O)N[C@H]1CC[C@H](CCN2CCCCC2c2coc3cccc-3c2)CC1

Procedure:
The title compound, white solid (65 mg, 63%), MS (ISP) m/z=413.4 [(M+H)+], mp 169° C., was prepared in accordance with the general method of example 1 from trans-4-[2-(4-benzofuran-3-yl-piperidin-1-yl)-ethyl]-cyclohexylamine dihydrochloride (intermediate A) (100 mg, 0.25 mmol) and 2-hydroxy-2-methyl-propionamide.
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)C(C)C)(C)C.[F:17][C:18]1[CH:26]=[C:25]([F:27])[C:24]([F:28])=[CH:23][C:19]=1[C:20](Cl)=[O:21]>ClCCl>[F:17][C:18]1[CH:26]=[C:25]([F:27])[C:24]([F:28])=[CH:23][C:19]=1[C:20]([O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:21]
Reactant: Oc1ccccc1
Reactant: O=C(Cl)c1cc(F)c(F)cc1F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C(Oc1ccccc1)c1cc(F)c(F)cc1F
Reaction time: 2 h

Procedure:
A solution of phenol (13.3 g, 141 mmol) in dry dichloromethane (370 mL) was cooled in ice bath and treated with N,N-diisopropylethylamine (34 mL, 129 mmol) followed by dropwise addition of 2,4,5-trifluorobenzoyl chloride over a period of 15 minutes. The ice bath was removed, stirring was continued for two hours at room temperature and the solution was then transferred to a separatory funnel and the organic layer was washed successively with hydrochloric acid solution (2N, 150 mL), saturated aqueous sodium bicarbonate solution, and brine, dried over anhydrous sodium sulfate, filtered and evaporated. The residue was triturated with hexane to yield an off-white solid product upon evaporation, and the hot hexane-soluble fraction of the resulting solid product was purified on silica in portions by eluting successively with hexane, and then 0-5% ether in hexane in a gradient fashion to yield phenyl 2,4,5-trifluorobenzoate as white solid.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([N+:16]([O-:18])=[O:17])[C:7](OC)=[C:8]2[C:13]=1[CH2:12][CH2:11][CH2:10][CH2:9]2)(=[O:3])[CH3:2].[NH3:19]>CS(C)=O>[C:1]([C:4]1[CH:5]=[C:6]([N+:16]([O-:18])=[O:17])[C:7]([NH2:19])=[C:8]2[C:13]=1[CH2:12][CH2:11][CH2:10][CH2:9]2)(=[O:3])[CH3:2]
Reactant: COc1c([N+](=O)[O-])cc(C(C)=O)c2c1CCCC2
Reactant: N
Solvent: CS(C)=O
Product: CC(=O)c1cc([N+](=O)[O-])c(N)c2c1CCCC2
Temperature: 0 °C
Yield: 75 %

Procedure:
A solution of 8-acetyl-1,2,3,4-tetrahydro-5-methoxy-6nitronaphthalene (1.0 g, 4 mmol) in 15 ml of dry dimethylsulfoxide was heated to 100° C. and ammonia was passed into the solution for 3 h. After the solution was added to 100 ml of ice-water, the crude solid was filtered off and washed with water. Recrystallization from ethanol afforded 0.71 g (75%) of the pure title compound M.p. 170°-172° C.; 1H-NMR (DMSO-d6): 1.47-1.93 (m, 4H, 2CH2), 2.27-2.63 (m, 2H, CH2), 2.48 (s, 3H, COCH3), 2.70-3.03 (m, 2H, CH2), 7.50 (broad s, 2H, NH2), 8.33 (s, 1H, H-7).
Reaction SMILES: [NH2:1][CH:2]1[N:8]=[C:7]([CH:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)[C:6]2[CH:14]=[CH:15][CH:16]=[CH:17][C:5]=2[N:4]([CH2:18][CH2:19][CH3:20])[C:3]1=[O:21].Cl[C:23]([O:25][C:26]1[CH:31]=[CH:30][C:29]([N+:32]([O-:34])=[O:33])=[CH:28][CH:27]=1)=[O:24]>>[CH:9]1([C:7]2[C:6]3[CH:14]=[CH:15][CH:16]=[CH:17][C:5]=3[N:4]([CH2:18][CH2:19][CH3:20])[C:3](=[O:21])[CH:2]([NH:1][C:23]([O:25][C:26]3[CH:27]=[CH:28][C:29]([N+:32]([O-:34])=[O:33])=[CH:30][CH:31]=3)=[O:24])[N:8]=2)[CH2:10][CH2:11][CH2:12][CH2:13]1
Reactant: CCCN1C(=O)C(N)N=C(C2CCCC2)c2ccccc21
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Product: CCCN1C(=O)C(NC(=O)Oc2ccc([N+](=O)[O-])cc2)N=C(C2CCCC2)c2ccccc21
Yield: 7.8 %

Procedure:
The title compound was prepared from 3(R,S)-amino-5-cyclopentyl-1,3-dihydro-1-propyl-2H-1,4-benzodiazepin-2-one (321 mg, 11.2 mmol) and 4-nitrophenyl chloroformate (229 mg, 11.4 mmol) using the procedure described in Example 20, Step 1. The crude product was triturated with ether (10 ml) to give the title compound (396 mg, 78%) as a white solid. 1H NMR (360 MHz, CDCl3) 0.83 (3H, t, J=7.4 Hz), 1.33-1.82 (8H, m), 1.97 (1H, m), 2.15 (1H, m), 3.34 (1H, m), 3.60 (1H, m), 4.32 (1H, m), 5.16 (1H, d, J=8.3 Hz), 6.89 (1H, d, J=8.4 Hz), 7.30-7.37 (4H, m), 7.52 (1H, t of d, J=7.8 and 1.6 Hz), 7.59 (1H, dd, J=7.8 and 1.5 Hz), 8.22 (2H, d, J=9.2 Hz).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([NH:12][C:13]2[CH:17]=[CH:16][NH:15][N:14]=2)[N:3]=1.[Cl:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1>>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH:5]=[C:4]([NH:12][C:13]3[CH:17]=[CH:16][NH:15][N:14]=3)[N:3]=2)=[CH:21][CH:20]=1
Reactant: Clc1nc(Nc2cc[nH]n2)cc2ccccc12
Reactant: OB(O)c1ccc(Cl)cc1
Product: Clc1ccc(-c2nc(Nc3cc[nH]n3)cc3ccccc23)cc1

Procedure:
Similar procedure as described in example 131 was used, starting from (1-chloro-isoquinolin-3-yl)-(1H-pyrazol-3-yl)-amine and 4-chloro-phenylboronic acid to give [1-(4-chloro-phenyl)-isoquinolin-3-yl]-(1H-pyrazol-3-yl)-amine. LC-MS m/e 321(MH+).
Reaction SMILES: [CH3:1][N:2]1[C:6]([CH2:7][C:8](O)=[S:9])=[N:5][N:4]=[N:3]1.S(Cl)([Cl:13])=O>CN(C)C=O.C1C=CC=CC=1>[CH3:1][N:2]1[C:6]([CH2:7][C:8]([Cl:13])=[S:9])=[N:5][N:4]=[N:3]1
Reactant: Cn1nnnc1CC(O)=S
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Solvent: c1ccccc1
Product: Cn1nnnc1CC(=S)Cl
Temperature: 50 °C

Procedure:
A solution of (1-methyl-1H-tetrazol-5-yl)-thioacetic acid (10 g) and thionyl chloride (10.2 g) in a mixture of dried benzene (130 ml) and dimethylformamide (1 drop) was warmed for 1.5 hours at 50° C. The solvent was distilled off and dried benzene was added to the residue. Excess thionyl chloride was removed by evaporating benzene to give crystals of (1-methyl-1H-tetrazol-5-yl)-thioacetyl chloride. A solution of the above obtained acid chloride in a mixture of dried benzene (70 ml) and dried chloroform (7 ml) was dropwise added over 30 minutes under stirring and ice cooling to a solution of 3,4-dimethoxyphenethylamine (8.0 g) and triethylamine (5.80 g) in a mixture of dried benzene (120 ml) and dried chloroform (15 ml). The mixture was stirred for 1 hour at the same temperature and further 1 hour at room temperature, after which the solvent was removed. The residue was dissolved in ethyl acetate and the solution was in turn washed with water, 5% hydrochloric acid, water, dilute sodium bicarbonate aqueous solution and water, and dried. The solvent was distilled off and the residual oil was crystallized by treating with ether. The crystals were collected by filtration and washed with ether to give N-(3,4-dimethoxyphenethyl)-(1-methyl-1H-tetrazol-5-yl)thioacetamide (9.7 g). The crystals were recrystallized from a mixture of ethyl acetate and ether to give colorless crystals of the object compound, mp 90° to 92° C.
Reaction SMILES: [C:1]([OH:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:10][S:11](O)(=[O:13])=[O:12].O=S(=O)=O.[Cl-].[Na+:20]>>[S:11]([C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=1)[C:1]([O-:9])=[O:8])([OH:13])(=[O:12])=[O:10].[Na+:20]
Reactant: O=S(=O)(O)O
Reactant: O=C(O)c1ccccc1
Agent: O=S(=O)=O
Agent: [Cl-]
Agent: [Na+]
Product: O=C([O-])c1cccc(S(=O)(=O)O)c1
Temperature: 130 °C
Reaction time: 1 h

Procedure:
122.1 g (1.0 mol) of benzoic acid are melted at 125° to 130° C. in a 1 l four-neck flask fitted with stirrer, internal thermometer and reflux condenser. Then 405 g of oleum are introduced over 30 minutes. Subsequently the reaction mixture is heated to 130° C. and stirred for a further 1 hour at this temperature. The reaction mixture is cooled and 1800 g (=1500 ml) of 26.4% strength sodium chloride solution are run in over 15 minutes. The reaction mixture is heated to 80° C. to 85° C. Then the mixture is allowed to cool to 50° C. while stirring. Subsequently it is cooled with an ice bath to <5° C. and stirred for a further 30 minutes at this temperature. The precipitated product is filtered off with suction and washed with 256 g (=250 ml) of 5% strength sodium chloride solution cooled to 5° C., in two portions. After drying, 204.4 g of sodium 3-sulfobenzoate are obtained with a purity of 96% and a sodium chloride content of 3% (corresponding to 196.3 g (0.88 mol) of 100% sodium 3-sulfobenzoate). 2342 g of effluent are produced.
Reaction SMILES: [CH3:1][CH:2]([CH2:5][CH:6]([CH3:14])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH2:3][OH:4].[H][H]>C1CCCCC1>[CH:8]1([CH2:7][CH:6]([CH3:14])[CH2:5][CH:2]([CH3:1])[CH2:3][OH:4])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1
Reactant: CC(CO)CC(C)Cc1ccccc1
Reactant: [H][H]
Solvent: C1CCCCC1
Product: CC(CO)CC(C)CC1CCCCC1
Reaction time: 18 h
Yield: 97 %

Procedure:
100 g of 2,4-Dimethyl-5-phenyl-pentanol (obtained as described in EP 0 908 439) combined with 2 g Ru on aluminium oxide (Ru content: 5 wt. %) were hydrogenated in 80 ml cyclohexane at a hydrogen pressure of 22 bar and at a temperature of 105° C. After 18 hours the reaction was finished. The catalyst was removed and the product distilled. 100 g (content: 99.5%) of 5-cyclohexyl-2,4-dimethyl-pentanol were obtained.
Reaction SMILES: [NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH3:21])[N:14]([CH2:15][CH2:16][CH2:17][C:18](=O)[CH3:19])[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.Cl.[CH2:23]([O:30][NH2:31])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[CH2:23]([O:30][N:31]=[C:18]([CH2:17][CH2:16][CH2:15][N:14]1[C:10]2[C:9]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[N:3]=[C:2]([NH2:1])[C:11]=2[N:12]=[C:13]1[CH3:21])[CH3:19])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: CC(=O)CCCn1c(C)nc2c(N)nc3ccccc3c21
Reactant: NOCc1ccccc1
Agent: Cl
Product: CC(CCCn1c(C)nc2c(N)nc3ccccc3c21)=NOCc1ccccc1

Procedure:
By the general method described in Part F of Example 30, 5-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)pentan-2-one was reacted with O-benzylhydroxylamine hydrochloride to provide 5-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)pentan-2-one O-benzyloxime) in about a 3 to 1 mixture of E and Z isomers as white crystals after recrystallization from a mixture of toluene and hexane, mp 146-148° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CC(C)=O>[CH2:15]([O:8][C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: BrCc1ccccc1
Reactant: Oc1ccc(Br)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: Brc1ccc(OCc2ccccc2)cc1
Yield: 78.2 %

Procedure:
4-Bromophenol (100 g, 0.587 mol) was dissolved in acetone (1100 ml), anhydrous potassium carbonate (159.53 g, 1.156 mmol) and benzyl bromide (103.78 g, 0.607 mol) were successively added thereto and the mixture was heated to reflux for 3 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The resulting crude product was recrystallized from hexane to give the title compound (120.76 g, 0.459 mol, 79%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][CH3:21])=[N:8][NH:9][C:10]2=O)=[CH:5][CH:4]=1.P(Cl)(Cl)([Cl:24])=O>>[Cl:24][C:10]1[C:11]2[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:12]=2)[C:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH3:21])=[N:8][N:9]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: COc1ccc2c(-c3ccccc3OC)n[nH]c(=O)c2c1
Product: COc1ccc2c(-c3ccccc3OC)nnc(Cl)c2c1

Procedure:
This compound is obtained according to the procedure described in 1.3. by reacting 7-methoxy-4-(2-methoxyphenyl)-2H-phthalazin-1-one with phosphoryl chloride.