Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1]N1C(=O)CCC1=O.[NH2:9][C:10]1[C:11]([NH:20][CH2:21][CH2:22][CH2:23][OH:24])=[C:12]([CH:17]=[CH:18][CH:19]=1)[C:13]([O:15][CH3:16])=[O:14]>C(#N)C.C(=O)([O-])O.[Na+]>[NH2:9][C:10]1[C:11]([NH:20][CH2:21][CH2:22][CH2:23][OH:24])=[C:12]([CH:17]=[CH:18][C:19]=1[Cl:1])[C:13]([O:15][CH3:16])=[O:14]
Reactant: COC(=O)c1cccc(N)c1NCCCO
Reactant: O=C1CCC(=O)N1Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Product: COC(=O)c1ccc(Cl)c(N)c1NCCCO
Temperature: 25 °C
Reaction time: 16 h
Yield: 16.4 %

Procedure:
N-Chlorosuccinimide (74.1 g, 555 mmol) was added to a stirred solution of methyl 3-amino-2-[(3-hydroxypropyl)amino]benzoate (81.9 g, 370 mmol) in acetonitrile (1480 mL) at room temperature, and the mixture was stirred at room temperature for 16 hr. Additional N-chlorosuccinimide (9.88 g, 74.0 mmol) was added to the mixture, and the mixture was stirred at room temperature for 90 min. The mixture was diluted with saturated aqueous sodium hydrogen carbonate, concentrated in vacuo, and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 20-45% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the title compound (15.7 g, 60.8 mmol, 16%).
Reaction SMILES: C[C:2]1(C)[O:9][CH2:8][CH2:7][C@H:6]2[N:3]1[C:4](=[O:13])[C@H:5]2[N:10]=[N+:11]=[N-:12].CC(C)=[O:17].OS(O)(=O)=O.O=[Cr](=O)=O.C(O)(C)C>CC(C)=O>[N:10]([C@H:5]1[C@H:6]([CH2:7][C:8]([O:9][CH3:2])=[O:17])[NH:3][C:4]1=[O:13])=[N+:11]=[N-:12]
Reactant: CC(C)=O
Reactant: CC1(C)OCC[C@@H]2[C@H](N=[N+]=[N-])C(=O)N21
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: CC(C)O
Product: COC(=O)C[C@@H]1NC(=O)[C@H]1N=[N+]=[N-]

Procedure:
In 30 ml of acetone is dissolved 330 mg of trans-2,2-dimethyl-7-azido-1-aza-3-oxabicyclo[4.2.0]octan-8-one and under ice-cooling and stirring, 3.3 ml (8N solution) of Jones reagent is added. The mixture is stirred for 2.5 hours, after which 5 ml of isopropyl alcohol is added and the mixture is further stirred for 10 minutes. The insolubles are filtered off with the aid of Celite and the filtrate is concentrated under reduced pressure. The residue is shaken with tetrahydrofuran and a small amount of saturated aqueous sodium chloride. The tetrahydrofuran layer is taken and extracted three times with tetrahydrofuran. The tetrahydrofuran layers are combined, dried over anhydrous sodium sulfate and, after addition of a solution of diazomethane in ether, the mixture is allowed to stand. The solvent is then distilled off and the residue is shaken with water and ethyl acetate. The ethyl acetate layer is taken, washed with aqueous sodium hydrogen carbonate and water in this order and dried over anhydrous sodium sulfate. It is concentrated under reduced pressure and the residue is purified by silica gel column chromatography to give trans-3-azido-4-methoxycarbonylmethyl-2-oxoazetidine.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:4]=[C:5]([CH2:9][CH:10]([O:16][CH:17]([CH3:19])[CH3:18])[C:11]([O:13]CC)=[O:12])[CH:6]=[CH:7][CH:8]=1.[F:20][C:21]([F:32])([F:31])[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([N:28]=[C:29]=[O:30])[CH:23]=1>>[CH:17]([O:16][CH:10]([CH2:9][C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([CH2:2][O:1][C:29]([NH:28][C:24]2[CH:25]=[CH:26][CH:27]=[C:22]([C:21]([F:20])([F:31])[F:32])[CH:23]=2)=[O:30])[CH:4]=1)[C:11]([OH:13])=[O:12])([CH3:18])[CH3:19]
Reactant: CCOC(=O)C(Cc1cccc(CO)c1)OC(C)C
Reactant: O=C=Nc1cccc(C(F)(F)F)c1
Product: CC(C)OC(Cc1cccc(COC(=O)Nc2cccc(C(F)(F)F)c2)c1)C(=O)O

Procedure:
Using ethyl 3-[3-(hydroxymethyl)phenyl]-2-isopropoxypropanoate and α,α,α-trifluoro-m-tolylisocyanate, the title compound was obtained in the same manner as described in Example 148.
Reaction SMILES: [F:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][CH:12]([CH:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[CH2:11][CH2:10]2)=[N:4][C:5]([CH3:8])=[N:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:28]1[N:33]=[CH:32][C:31](F)=[CH:30][N:29]=1>CN1C(=O)CCC1.C(OCC)(=O)C>[F:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][CH:12]([CH:15]3[CH2:20][CH2:19][N:18]([C:28]4[N:33]=[CH:32][CH:31]=[CH:30][N:29]=4)[CH2:17][CH2:16]3)[CH2:11][CH2:10]2)=[N:4][C:5]([CH3:8])=[N:6][CH:7]=1
Reactant: Fc1cnc(Cl)nc1
Reactant: Cc1ncc(F)c(N2CCC(C3CCNCC3)CC2)n1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN1CCCC1=O
Solvent: CCOC(C)=O
Product: Cc1ncc(F)c(N2CCC(C3CCN(c4ncccn4)CC3)CC2)n1
Temperature: 110 °C

Procedure:
1-(5-fluoro-2-methylpyrimidin-4-yl)-4,4′-bipiperidine (10 mg, 0.036 mmol) and cesium carbonate (35 mg, 0.11 mmol) were stirred in NMP (2 ml) and 2-chloro-5-fluoropyrimidine (8.2 mg, 0.72 mmol) was added. The mixture was heated at 110° C. for 2 h. The reaction was cooled down to r.t. and diluted with ethyl acetate (5 mL) and was washed with water 2 mL (×1) and brine 2 mL (×1). The organic phase was dried over magnesium sulfate, filtered, and concentrated on rotavapor. The crude material was purified by preparative TLC with 30% acetone: hexane to yield the titled compound.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-])=O)=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].C([O-])([O-])=O.[K+].[K+].[CH2:20](Br)[CH:21]=[CH2:22].O>CN(C=O)C>[NH2:11][C:8]1[CH:9]=[CH:10][C:2]([F:1])=[C:3]([CH:7]=1)[C:4]([O:6][CH2:22][CH:21]=[CH2:20])=[O:5]
Reactant: C=CCBr
Reactant: O=C(O)c1cc([N+](=O)[O-])ccc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: C=CCOC(=O)c1cc(N)ccc1F

Procedure:
2-Fluoro-5-nitrobenzoic acid (4.16 g, 22.5 mM) was dissolved in DMF (45 ml), and anhydrous K2CO3 (4.65 g, 33.7 mM) added with stirring. Allyl bromide (2.38 ml, 28.1 mM) was run in, the mixture was stirred for 18 hours at ambient temperature before being poured into water (450 ml) and extracted with diethyl ether (3×100 ml). The combined extracts were dried over MgSO4, and evaporated to give a yellow oil (5.4 g). The oil was purified by chromatography on silica, eluting with a mixture of ethyl acetate/hexane (12.5:87.5), to give allyl 2-fluoro-5-nitrobenzoate (4.64 g, 92%). Nmr (CDCl3): δ 4.89 (d, 2H); 5.30-5.50 (m, 2H); 5.90-6.10 (m, 1H); 7.32 (t, 1H); 8.38-8.46 (m, 1H); 8.86 (dd, 1H).
Reaction SMILES: [OH:1][C:2]1[C:10]([OH:11])=[C:9]([O:12][CH3:13])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[CH2:14](Br)[CH2:15]Br>O>[CH3:13][O:12][C:9]1[C:10]2[O:11][CH2:14][CH2:15][O:1][C:2]=2[C:3]([C:4]([OH:6])=[O:5])=[CH:7][CH:8]=1
Reactant: COc1ccc(C(=O)O)c(O)c1O
Reactant: BrCCBr
Solvent: O
Product: COc1ccc(C(=O)O)c2c1OCCO2
Yield: 57 %

Procedure:
171.5 g of 2,3-dihydroxy-4-methoxy benzoic acid, 515 cm3 of alcohol, 280 cm3 of soda lye and 175 g of ethylene bromide were introduced into a balloon flask provided with an agitator, a thermometer and an inlet pipe for nitrogen. The mixture was heated under reflux and then cooled and poured into 2.8 liters of water. The solution was filtered and treated with 85 cm3 of concentrated hydrochloric acid. The pecipitate was dried off, washed and dried. After recrystallization in dimethylformamide, 110 g, of 8-methoxy-1,4-benzodioxane-5-carboxylic acid were obtained (M.P.: 224°-226° C.; yield: 57%).
Reaction SMILES: [Br:1][C:2]1[C:22]([OH:23])=[CH:21][C:5]2[C:6]([C:9]([C:11]3[CH:16]=[C:15]([F:17])[C:14]([O:18][CH3:19])=[C:13]([F:20])[CH:12]=3)=[O:10])=[CH:7][O:8][C:4]=2[C:3]=1[Br:24].[N+]([O-])(O)=[O:26].O>CC(O)=O>[Br:1][C:2]1[C:22](=[O:23])[C:21](=[O:26])[C:5]2[C:6]([C:9](=[O:10])[C:11]3[CH:16]=[C:15]([F:17])[C:14]([O:18][CH3:19])=[C:13]([F:20])[CH:12]=3)=[CH:7][O:8][C:4]=2[C:3]=1[Br:24]
Reactant: COc1c(F)cc(C(=O)c2coc3c(Br)c(Br)c(O)cc23)cc1F
Reactant: O=[N+]([O-])O
Solvent: CC(=O)O
Solvent: O
Product: COc1c(F)cc(C(=O)c2coc3c2C(=O)C(=O)C(Br)=C3Br)cc1F
Temperature: 60 °C
Yield: 90.5 %

Procedure:
To a solution of (6,7-dibromo-5-hydroxybenzofuran-3-yl)(3,5-difluoro-4-methoxyphenyl)methanone (30 mg, 0.065 mmol) in AcOH (1 mL) was added nitric acid—69% (20.03 μl, 0.325 mmol) at room temperature. The mixture was heated to 60° C. for 3 hours, cooled to room temperature, poured onto iced water and the suspension filtered. A red/orange solid was isolated which was dried under vacuum to afford the product (28 mg, 91%).
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([CH2:8][N:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=[O:19])[C:11]([C:20]([C:22]3[CH:23]=[N:24][C:25](Cl)=[CH:26][CH:27]=3)=[O:21])=[CH:10]2)[CH:5]=[CH:4][CH:3]=1.[CH3:29][O-:30].[Na+]>CO>[Br:1][C:2]1[N:7]=[C:6]([CH2:8][N:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=[O:19])[C:11]([C:20]([C:22]3[CH:23]=[N:24][C:25]([O:30][CH3:29])=[CH:26][CH:27]=3)=[O:21])=[CH:10]2)[CH:5]=[CH:4][CH:3]=1
Reactant: O=C(c1ccc(Cl)nc1)c1cn(Cc2cccc(Br)n2)c2ccccc2c1=O
Reactant: C[O-]
Agent: [Na+]
Solvent: CO
Product: COc1ccc(C(=O)c2cn(Cc3cccc(Br)n3)c3ccccc3c2=O)cn1

Procedure:
Experimental conditions analogous to those described for Example 141, from 38 mg (0.084 mmol) of 1-(6-bromo-pyridin-2-ylmethyl)-3-(6-chloro-pyridine-3-carbonyl)-1H-quinolin-4-one, 90 mg (1.67 mmol) of sodium methoxide and 1 mL dry methanol. Yield: 19 mg of a white powder. LC-MSD, m/z for C22H16BrN3O3 [M+H]+=450.0, 452.0; HPLC retention time: 2.3 min.
Reaction SMILES: [Cl:1][C:2]1[CH:13]=[C:12]([N+:14]([O-])=O)[C:11]([N+:17]([O-])=O)=[CH:10][C:3]=1[C:4]([NH:6][CH:7]1[CH2:9][CH2:8]1)=[O:5].[Cl-].[NH4+]>C(O)C.O.[Fe]>[NH2:14][C:12]1[C:11]([NH2:17])=[CH:10][C:3]([C:4]([NH:6][CH:7]2[CH2:9][CH2:8]2)=[O:5])=[C:2]([Cl:1])[CH:13]=1
Reactant: O=C(NC1CC1)c1cc([N+](=O)[O-])c([N+](=O)[O-])cc1Cl
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: Nc1cc(Cl)c(C(=O)NC2CC2)cc1N
Temperature: 60 °C
Yield: 67.4 %

Procedure:
2-Chloro-N-cyclopropyl-4,5-dinitrobenzamide (7.5 g, 26.3 mmol) was initially charged in ethanol (200 ml) and water (40 ml). At room temperature, ammonium chloride (2.53 g, 47.4 mmol) was added and the reaction mixture was heated to 60° C. At this temperature, iron powder (14.7 g, 263 mmol) was added in portions and the reaction mixture was then heated under reflux for 4 h. The ethanol was removed under reduced pressure and the remaining aqueous suspension was filtered through Celite. The filtrate was extracted three times with ethyl acetate, and the combined organic phases were washed with saturated sodium chloride solution and dried over sodium sulphate. After removing the solvent under reduced pressure, 4 g (68% of theory) of 4,5-diamino-2-chloro-N-cyclopropylbenzamide were obtained. 1H NMR (D6-DMSO): δ 0.44-0.48 (m, 2H), 0.61-0.64 (m, 2H), 2.71-2.75 (m, 1H), 4.68 (bs, 2H), 4.98 (bs, 2H), 6.47 (s, 1H), 6.55 (s, 1H), 7.95-7.97 (d, 1H).
Reaction SMILES: [Br:1][CH:2]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[C:3](Cl)=[O:4].[OH:16][CH:17]1[O:36][C@H:35]([CH2:37][OH:38])[C@@H:22]([O:23][C@@H:24]2[O:32][C@H:31]([CH2:33][OH:34])[C@H:29]([OH:30])[C@H:27]([OH:28])[C@H:25]2[OH:26])[C@H:20]([OH:21])[C@H:18]1[NH2:19].O.C(=O)([O-])[O-].[Na+].[Na+]>C(O)CCC>[Br:1][CH:2]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[C:3]([C:17]1([O:36][C@H:35]([CH2:37][OH:38])[C@@H:22]([O:23][C@@H:24]2[O:32][C@H:31]([CH2:33][OH:34])[C@H:29]([OH:30])[C@H:27]([OH:28])[C@H:25]2[OH:26])[C@H:20]([OH:21])[C@H:18]1[NH2:19])[OH:16])=[O:4]
Reactant: CCCCCCCCCCC(Br)C(=O)Cl
Reactant: N[C@H]1C(O)O[C@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)[C@@H]1O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCCCO
Solvent: O
Product: CCCCCCCCCCC(Br)C(=O)C1(O)O[C@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1N
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Alpha-bromolauroyl chloride (0.50 g) was added drop-wise to a 30% aqueous solution of lactosamine (0.7 g) at zero degrees centigrade. The pH of the solution was kept above 9.0 by adding saturated sodium carbonate water solution. The reaction was stirred overnight at room temperature. It was then heated to 36° C. for an additional hour. The final product was obtained by extraction two times with n-butanol. After evaporating butanol, the remaining solid material was washed with cold ethanol. The final product was collected by filtration. The NMR spectra showed that the solid material is the expected product. The yield of the reaction was 75%.
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:5]=[C:6]([C:10](=[O:12])[CH3:11])[CH:7]=[CH:8][CH:9]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1.O>[F:1][C:2]([F:13])([F:14])[O:3][C:4]1[CH:5]=[C:6]([CH:10]([OH:12])[CH3:11])[CH:7]=[CH:8][CH:9]=1
Reactant: CC(=O)c1cccc(OC(F)(F)F)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: CC(O)c1cccc(OC(F)(F)F)c1
Temperature: 25 °C

Procedure:
To a solution of 1-(3-Trifluoromethoxyphenyl)ethanone (1.00 g, 4.90 mmol) in THF (5 mL) at 0° C. was added 1M LiAlH4 in THF (5.9 mL, 5.9 mmol), and the solution was allowed to warm to rt. A few drops of water were added to quench. The mixture was concentrated in vacuo, transferred to a separatory funnel, and extracted using DCM and sat. aq. Rochelle salt. The organic layer was concentrated in vacuo to afford the title compound as a clear oil.
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.CS(O[CH2:20][C:21]1([C:24]#[N:25])[CH2:23][CH2:22]1)(=O)=O.[H-].[Na+]>CN(C)C=O.C(OCC)(=O)C>[CH3:1][C:2]1([CH3:14])[C:6]([CH3:7])([CH3:8])[O:5][B:4]([C:9]2[CH:13]=[N:12][N:11]([CH2:20][C:21]3([C:24]#[N:25])[CH2:23][CH2:22]3)[CH:10]=2)[O:3]1
Reactant: CS(=O)(=O)OCC1(C#N)CC1
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC1(C)OB(c2cnn(CC3(C#N)CC3)c2)OC1(C)C
Temperature: 110 °C
Reaction time: 2 h
Yield: 109.8 %

Procedure:
A mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.1 g, 0.5 mmol), (1-cyanocyclopropyl)methyl methanesulfonate (0.14 g, 0.77 mmol), and sodium hydride (31 mg, 0.77 mmol) in N,N-dimethylformamide (1 mL) was stirred at 110° C. for 2 h. After cooling, it was diluted with ethyl acetate, washed with water and brine, dried over Na2SO4. After filtration the filtrate was concentrated to yield 0.15 g of the crude product which was used in the next step reaction without further purification.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([NH:11][C:12](=[O:23])[C:13]2[CH:18]=[CH:17][C:16]([C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=2)=[S:10])=[CH:4][CH:3]=1.[Br:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][C:30](Cl)=[O:31].C(N(CC)CC)C>C(Cl)Cl>[C:19]([C:16]1[CH:15]=[CH:14][C:13]([C:12]([NH:11][C:9](=[S:10])[NH:8][C:5]2[CH:6]=[CH:7][C:2]([NH:1][C:30](=[O:31])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][Br:24])=[CH:3][CH:4]=2)=[O:23])=[CH:18][CH:17]=1)([CH3:20])([CH3:22])[CH3:21]
Reactant: O=C(Cl)CCCCCBr
Reactant: CC(C)(C)c1ccc(C(=O)NC(=S)Nc2ccc(N)cc2)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)c1ccc(C(=O)NC(=S)Nc2ccc(NC(=O)CCCCCBr)cc2)cc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 53.9 %

Procedure:
Thiourea 4 (200 mg, 0.61 mmol, 1 equiv.) was stirred in CH2Cl2 (10 mL) under N2 atmosphere. 6-Bromohexanoyl chloride (195.8 mg, 0.92 mmol, 1.5 equiv.) was added, followed by triethylamine (85 μL, 0.61 mmol, 1 equiv.). The beige suspension was stirred at rt for 1.5 h and diluted with CH2Cl2 (10 mL). The organic solution was washed with 1 M aqueous hydrochloric acid (1×10 mL), 10% aqueous sodium hydroxide (1×50 mL), and saturated brine (1×10 mL). The organic phase was dried over MgSO4 and concentrated in vacuo. The resulting brown foam was purified by flash chromatography on silica (50% ethyl acetate/petroleum ether) to give 6-bromo-hexanoic acid {4-[3-(4-tert-butyl-benzoyl)-thioureido]-phenyl}-amide (166 mg, 55%) as a yellow oil.
Reaction SMILES: [OH:1][C:2]1[C:7]([CH3:8])=[C:6]([CH3:9])[CH:5]=[C:4]([CH3:10])[C:3]=1[CH:11](O)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][OH:17].[H][H]>C(O)(=O)C.[Pd]>[OH:1][C:2]1[C:7]([CH3:8])=[C:6]([CH3:9])[CH:5]=[C:4]([CH3:10])[C:3]=1[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][OH:17]
Reactant: Cc1cc(C)c(C(O)CCCCCO)c(O)c1C
Reactant: [H][H]
Agent: [Pd]
Solvent: CC(=O)O
Product: Cc1cc(C)c(CCCCCCO)c(O)c1C

Procedure:
A solution of 1-(2'-hydroxy-3',4',6'-trimethylphenyl)-1,6-hexanediol (formula III-3 wherein R=H3C, X=H, Y=OH, n=4, in the free form) (5.43 parts) in acetic acid (150 volume parts) was stirred with 5% palladium on carbon (4.79 parts) under a stream of hydrogen gas at room temperature until the uptake of hydrogen ceased. The catalyst was filtered off and the filtrate was concentrated in vacuo. The resulting residue was subjected to column chromatography on silica gel and eluted with chloroform-methanol (100:1). From the 1st fraction, 6-(2'-hydroxy-3',4',6'-trimethylphenyl)hexanol (formula III-2, wherein R=H3C, X=H, Y=OH, n=4, in the free form) (0.872 part) was obtained as colorless needles melting at 81°-82° C.
Reaction SMILES: C1(O[C:8](=[O:22])[NH:9][C:10]2[C:11]([O:19][CH2:20][CH3:21])=[N:12][C:13]([CH3:18])=[C:14]([CH2:16][CH3:17])[CH:15]=2)C=CC=CC=1.[CH3:23][O:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1>>[CH2:20]([O:19][C:11]1[C:10]([NH:9][C:8]([N:34]2[CH2:33][CH2:32][N:31]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=3[O:24][CH3:23])[CH2:36][CH2:35]2)=[O:22])=[CH:15][C:14]([CH2:16][CH3:17])=[C:13]([CH3:18])[N:12]=1)[CH3:21]
Reactant: CCOc1nc(C)c(CC)cc1NC(=O)Oc1ccccc1
Reactant: COc1ccccc1N1CCNCC1
Product: CCOc1nc(C)c(CC)cc1NC(=O)N1CCN(c2ccccc2OC)CC1
Yield: 82 %

Procedure:
Phenyl-N-(2-ethoxy-5-ethyl-6-methylpyridin-3-yl)carbamate and 1-(2-methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound.
Reaction SMILES: [C:1]1(/[CH:7]=[CH:8]/[S:9](Cl)(=[O:11])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN(C1C=CC=CN=1)C.[NH2:22][C:23]1[N:27]([CH3:28])[N:26]=[C:25]([O:29][CH2:30][CH2:31][OH:32])[C:24]=1[C:33]1[CH:41]=[CH:40][C:36]2[O:37][CH2:38][O:39][C:35]=2[CH:34]=1>N1C=CC=CC=1>[O:37]1[C:36]2[CH:40]=[CH:41][C:33]([C:24]3[C:25]([O:29][CH2:30][CH2:31][OH:32])=[N:26][N:27]([CH3:28])[C:23]=3[NH:22][S:9](/[CH:8]=[CH:7]/[C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)(=[O:11])=[O:10])=[CH:34][C:35]=2[O:39][CH2:38]1
Reactant: O=S(=O)(Cl)/C=C/c1ccccc1
Reactant: Cn1nc(OCCO)c(-c2ccc3c(c2)OCO3)c1N
Agent: CN(C)c1ccccn1
Solvent: c1ccncc1
Product: Cn1nc(OCCO)c(-c2ccc3c(c2)OCO3)c1NS(=O)(=O)/C=C/c1ccccc1
Reaction time: 24 h
Yield: 80.3 %

Procedure:
(E)-2-phenylethensulfonyl chloride (381 mg) and dimethylaminopyridine (77 mg) were added at room temperature under an atmosphere of nitrogen to a solution of 2-{[5-amino-4-(1,3-benzodioxol-5-yl)-1-methyl-1H-pyrazol-3-yl]oxy}-1-ethanol (200 mg) (Preparation 45) in anhydrous pyridine (6 ml). After 24 h, the mixture was concentrated under reduced pressure. To the yellow solid was added water (30 ml), an aqueous solution of HCl (1N) to acidify the solution and the mixture was extracted with dichloromethane (3×30 ml). The organic fractions were combined, dried on sodium sulfate and concentrated under reduced pressure. The residue was dissolved in ethanol (6 ml) and dichloromethane (1 ml) and an excess of an aqueous solution of sodium hydroxyde (2N) was added. The reaction was stirred overnight. The reaction mixture was then diluted with dichloromethane (100 ml), acidified with an aqueous solution of HCl (1N). The phases were separated and the aqueous phase was extracted with dichloromethane (2×50 ml). The combined organic fractions were dried on sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica, 20 g) eluted with dichloromethane:methanol (95:5) to yield the title compound as colourless solid (257 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=[N:19][CH3:20])[CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].C(OCC)(=O)C.[H][H]>[Ni].ClC1C=CC=CC=1Cl>[CH3:20][NH:19][C@@H:12]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=2[C@H:9]([C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=2)[CH2:10][CH2:11]1
Reactant: CN=C1CCC(c2ccc(Cl)c(Cl)c2)c2ccccc21
Reactant: [H][H]
Agent: [Ni]
Solvent: Clc1ccccc1Cl
Solvent: CCOC(C)=O
Product: CN[C@H]1CC[C@@H](c2ccc(Cl)c(Cl)c2)c2ccccc21
Yield: 0.78 %

Procedure:
N-[4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H) naphthalenylidene]methanamine (Ketimine) (50 g), Ethyl acetate (300 ml), Raney Nickel (0.15 g wet basis) and o-dichlorobenzene (25 ml) are charged into a reaction vessel. The mixture is hydrogenated at 5 to 6 kg/cm2 over pressure of hydrogen for 6 to 7 hrs at about 28 to 30° C. The catalyst is removed by filtration and the cake is washed with 50 ml ethyl acetate. The amount of dehalogenated by product is <0.1%. Sertraline racemate free base thus formed is treated with hydrochloric acid (24 ml, 33%) and predominantly isomer of sertraline HCl racemate is filtered [Cis>98%, trans<2%, dehalogenation product<0.1%, yield 0.78 to 0.80%].
Reaction SMILES: Cl[C:2]1[N:6]([CH:7]2[CH2:12][CH2:11][N:10]([C:13]3([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[CH2:9][CH2:8]2)[C:5]2[CH:26]=[CH:27][CH:28]=[CH:29][C:4]=2[N:3]=1.[C:30]([O:34][C:35]([N:37]1[CH:42]2[CH2:43][CH2:44][CH:38]1[CH2:39][NH:40][CH2:41]2)=[O:36])([CH3:33])([CH3:32])[CH3:31]>CO>[C:20]1([C:13]2([N:10]3[CH2:11][CH2:12][CH:7]([N:6]4[C:5]5[CH:26]=[CH:27][CH:28]=[CH:29][C:4]=5[N:3]=[C:2]4[N:40]4[CH2:41][CH:42]5[N:37]([C:35]([O:34][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:36])[CH:38]([CH2:44][CH2:43]5)[CH2:39]4)[CH2:8][CH2:9]3)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: Clc1nc2ccccc2n1C1CCN(C2(c3ccccc3)CCCCCC2)CC1
Reactant: CC(C)(C)OC(=O)N1C2CCC1CNC2
Solvent: CO
Product: CC(C)(C)OC(=O)N1C2CCC1CN(c1nc3ccccc3n1C1CCN(C3(c4ccccc4)CCCCCC3)CC1)C2
Temperature: 120 °C
Reaction time: 96 h
Yield: 73.9 %

Procedure:
A mixture of 2-chloro-1-[1-(1-phenylcycloheptyl)-4-piperidinyl]-1H-benzimidazole (0.12 g, 0.294 mmol), 8-t-butoxycarbonyl-3,8-diazabicyclo[3.2.1]octane (0.12 g, 0.565 mmol,: D.Barlocco et al, J. Med. Chem. 1998, 41, 674), and methanol (1.5 ml) was stirred in a sealed tube at 120° C. for 4 days. After cooling down to room temperature, the reaction mixture was concentrated and purified by preparative TLC (1 mm plate×2, developed by CH2Cl2/MeOH: 10/1) to give 0.1269 g (74%) of an oil.
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][C:6]([N+:12]([O-])=O)=[CH:7][CH:8]=2)[NH:3]1.CCO>[Pd].CCOC(C)=O>[NH2:12][C:6]1[CH:5]=[C:4]2[C:9]([CH2:10][CH2:11][C:2]([CH3:15])([CH3:1])[NH:3]2)=[CH:8][CH:7]=1
Reactant: CC1(C)CCc2ccc([N+](=O)[O-])cc2N1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Product: CC1(C)CCc2ccc(N)cc2N1
Reaction time: 6 h
Yield: 99.6 %

Procedure:
In a 200-mL r.b. flask, a solution of 1,2,3,4-tetrahydro-2,2-dimethyl-7-nitroquinoline (1.00 g, 4.84 mmol) in 1:1 EtOH:EtOAc (40 mL) was treated with 10% Pd/C (0.20 g). The reaction mixture was de-gassed and fitted with a balloon of H2. The reaction mixture was stirred for 6 h, de-gassed, and filtered through a pad of Celite. The pad was rinsed with EtOAc (300 mL). The filtrate was concentrated to afford 0.85 g (99%) of the crude aniline as a reddish oil. Data for 7-amino-1,2,3,4-tetrahydro-2,2-dimethylquinoline: 1H NMR (400 MHz, CDCl3) 6.77 (d, J=7.9, 1H), 6.00 (dd, J=7.9, 2.2, 1H), 5.81 (d, J=2.2, 1H), 3.47 (bs, 1H) 3.40 (bs, 2H), 2.66 (t, J=6.7, 2H), 1.65 (t, J=6.7, 2H), 1.18 (s, 6H).