Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][NH2:19])[CH2:11][CH2:10]1.BrCCCCN1[C:29](=[O:30])[C:28]2=[CH:31][CH:32]=[CH:33][CH:34]=[C:27]2[C:26]1=[O:35].COC1C=CC=CC=1N1CCNCC1>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:10][CH2:11][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][N:19]2[C:29](=[O:30])[C:28]3=[CH:31][CH:32]=[CH:33][CH:34]=[C:27]3[C:26]2=[O:35])[CH2:13][CH2:14]1
Reactant: O=C1c2ccccc2C(=O)N1CCCCBr
Reactant: COc1ccccc1N1CCN(CCCCN)CC1
Agent: COc1ccccc1N1CCNCC1
Product: COc1ccccc1N1CCN(CCCCN2C(=O)c3ccccc3C2=O)CC1
Yield: 84.3 %

Procedure:
4-[4-(2-methyloxyphenyl)piperazinyl]butylamine: according to the method of claim 1, N-(4-bromobutyl)phthalimide and 2-methyloxyphenyl-piperazine was used in reaction to produce N-{4-[4-(2-methyloxyphenyl)piperazinyl]butyl}phthalimide, which was then reacted with hydrazine hydrate. The yield was: 84.3%. Hydrochloride salt had a mp: 173-175° C.
Reaction SMILES: [CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].F[C:12]1[CH:17]=[C:16](F)[CH:15]=[CH:14][C:13]=1[N+:19]([O-:21])=[O:20]>CN(C)C=O>[CH2:1]([O:8][C:12]1[CH:17]=[C:16]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:15]=[CH:14][C:13]=1[N+:19]([O-:21])=[O:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=[N+]([O-])c1ccc(F)cc1F
Reactant: OCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1ccc(OCc2ccccc2)cc1OCc1ccccc1
Reaction time: 0.5 h
Yield: 34.1 %

Procedure:
Benzyl alcohol (5.4 g) is added slowly to a stirred suspension of sodium hydride (2 g, 60% dispersion in mineral oil) in dry dimethylformamide (100 mL). The mixture is stirred for 30 minutes then 2,4-difluoronitrobenzene (3.2 g) is added in one portion. The resulting black solution is stirred at room temperature for 18 hours ,evaporated and the residue partitioned between ether (200 mL) and water (100 mL). The organic phase is washed thoroughly with water, dried and evaporated. The residue is triturated with hot ethanol (50 mL) and the mixture cooled in an ice-bath. The insoluble material is purified by filtration through a bed of silica eluting with a mixture of dichloromethane and petroleum ether, b.p.40-60° C., (1:1 v/v). The filtrate is evaporated and the solid crystallised from ethanol to give 2,4-dibenzyloxynitrobenzene (2.3 g) as a cream coloured solid, m.p. 101-103° C. [Elemental analysis:- C,71.4; H,5.07; N,4.09%. Calculated:- C,71.6; H,5.11; N,4.18%].
Reaction SMILES: [CH2:1]([SH:4])[CH2:2][CH3:3].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C1COCC1.Cl[C:21]1[N:25]([C:26]2[CH:27]=[C:28]([CH:33]=[CH:34][CH:35]=2)[C:29]([O:31][CH3:32])=[O:30])[N:24]=[CH:23][C:22]=1[C:36](=[O:44])[NH:37][CH:38]1[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1>CN(C=O)C.C(OCC)(=O)C>[CH:38]1([NH:37][C:36]([C:22]2[CH:23]=[N:24][N:25]([C:26]3[CH:27]=[C:28]([CH:33]=[CH:34][CH:35]=3)[C:29]([O:31][CH3:32])=[O:30])[C:21]=2[S:4][CH2:1][CH2:2][CH3:3])=[O:44])[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1
Reactant: COC(=O)c1cccc(-n2ncc(C(=O)NC3CCCCC3)c2Cl)c1
Reactant: CCCS
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCCSc1c(C(=O)NC2CCCCC2)cnn1-c1cccc(C(=O)OC)c1
Reaction time: 2 h

Procedure:
Propane thiol (48 mg, 0.57 mmol) was dissolved in DMF (3 mL) and treated at ambient temperature with a 1M solution of NaHMDS in THF (0.63 mL, 0.63 mmol). After stirring for 15 min a solution of methyl 3-[5-chloro-4-(cyclohexylcarbamoyl)pyrazol-1-yl]benzoate (Intermediate #19) (205 mg, 0.57 mmol) in DMF (5 mL) was added and stirring continued for 2 h. Ethyl acetate (50 mL) was added and the mixture washed with water (3×20 mL), dried (MgSO4) and evaporated to give an oil which was purified by chromatography on silica gel eluting with an EtOAc/DCM gradient (0-25%) to provide the title compound as a clear colourless oil. (175 mg, 75%)
Reaction SMILES: [CH2:1]([Li])[CH2:2][CH2:3][CH3:4].[CH:6]([CH:9]1[CH:13]([C:14]([F:17])([F:16])[F:15])[O:12][C:11](=[O:18])[NH:10]1)([CH3:8])[CH3:7]>CCCCCC.C1COCC1>[CH:6]([C@H:9]1[C@H:13]([C:14]([F:15])([F:17])[F:16])[O:12][C:11](=[O:18])[N:10]1[C:11]([O:18][C@H:1]1[C@H:9]([CH:6]([CH3:8])[CH3:7])[CH2:13][CH2:14][C@@H:3]([CH3:4])[CH2:2]1)=[O:12])([CH3:8])[CH3:7]
Reactant: CC(C)C1NC(=O)OC1C(F)(F)F
Reactant: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)N1C(=O)O[C@@H](C(F)(F)F)[C@@H]1C(C)C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
n-Butyllithium (20 ml of a 10M solution in hexane) was added to a solution of (4RS),5SR)-4-isopropyl-5-trifluoromethyl-oxazolidin-2-one (35.8 g) in THF (600 ml) at -78° C., followed by stirring for 0.5 hours. (-)-Menthyl chloroformate (41 ml, freshly distilled) was added followed by continuation of stirring at -78° C. for 0.5 hours. The solution was warmed to 25° C. and the reaction quenched by addition of saturated aqueous sodium bicarbonate solution. The product was extracted into ether and washed with water and brine. The solution was dried (MgSO4) and the solvent removed under vacuum. The resulting oil crystallized upon standing to give a solid which was collected by filtration. The solid was washed with ether:hexane (1:1) and dried to give (4S,5R)-4-isopropyl-3-[(1R,3R,4S)-3-p-menthyloxycarbonyl]-5-trifluoromethyloxazolidin-2-one (23.15 g); m.p. 138-140° C.; 1H NMR (300 MHz, DMSO):5.51 (dd, 1H), 4.68 (m, 1H), 4.26 (m, 1H), 2.27 (m, 1H), 1.94 (d, 1H), 1.78 (m, 1H), 1.62 (d, 2H), 1.42 (m, 2H), 1.01 (dd, 2H), 0.95-0.84 (m, 24H), 0.71 (d, 3H); 19FNMR (376.5 MHz,DMSO): -76.9910; 99% d.e. (A further crop of 4.3 g (99% d.e.) was obtained from the mother liquor). [Note: the (4R,5S) isomer has m.p. 80-82° C. and 19FNMR (376.5 MHz, DMSO): -77.0019.
Reaction SMILES: [O:1]=[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][N:6]=[CH:7][CH:8]=2)[N:3]1[CH2:12][CH:13]=O.[O:15]1[C:20]2[CH:21]=[CH:22][C:23]([CH2:25][N:26]([CH:34]3[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]3)[C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:24][C:19]=2[O:18][CH2:17][CH2:16]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.O>[O:15]1[C:20]2[CH:21]=[CH:22][C:23]([CH2:25][N:26]([CH:34]3[CH2:39][CH2:38][N:37]([CH2:13][CH2:12][N:3]4[C:4]5[C:9](=[CH:8][CH:7]=[N:6][CH:5]=5)[CH:10]=[CH:11][C:2]4=[O:1])[CH2:36][CH2:35]3)[C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:30])[CH3:31])=[CH:24][C:19]=2[O:18][CH2:17][CH2:16]1
Reactant: CC(C)(C)OC(=O)N(Cc1ccc2c(c1)OCCO2)C1CCNCC1
Reactant: O=CCn1c(=O)ccc2ccncc21
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)N(Cc1ccc2c(c1)OCCO2)C1CCN(CCn2c(=O)ccc3ccncc32)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 17 %

Procedure:
To a solution of 0.32 g of (2-oxo-1,7-naphthyridin-1(2H)-yl)acetaldehyde in 10 mL of dichloromethane, 0.59 g of tert-butyl (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(piperidin-4-yl)carbamate and 97 μL of acetic acid were added, then, 0.54 g of sodium triacetoxyborohydride was added to the reaction mixture, and the mixture was stirred at room temperature for 2 hours 30 minutes. Thereto were added water, a saturated aqueous sodium hydrogen carbonate solution and chloroform, the organic layer was separated, and the aqueous layer was extracted with chloroform. The organic layer and the extract were combined, the resultant solution was washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography using an eluent of chloroform:methanol=100:1 to obtain 0.15 g of tert-butyl (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(1-(2-(2-oxo-1,7-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate as a colorless oily substance.
Reaction SMILES: [NH2:1][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[CH3:11])[CH2:3]1.C(N(CC)CC)C.[F:19][C:20]1[CH:28]=[CH:27][C:23]([C:24](Cl)=[O:25])=[CH:22][CH:21]=1>O1CCOCC1>[F:19][C:20]1[CH:28]=[CH:27][C:23]([C:24]([NH:1][CH:2]2[CH2:10][C:9]3[C:4](=[CH:5][CH:6]=[CH:7][C:8]=3[CH3:11])[CH2:3]2)=[O:25])=[CH:22][CH:21]=1
Reactant: O=C(Cl)c1ccc(F)cc1
Reactant: Cc1cccc2c1CC(N)C2
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: Cc1cccc2c1CC(NC(=O)c1ccc(F)cc1)C2
Temperature: 25 °C
Reaction time: 2 h

Procedure:
370 mg (2.52 mmol) 2-amino-4-methylindane and 257 mg (2.52 mmol) triethylamine were dissolved in 5 ml dioxane, 400 mg (2.52 mmol) 4-fluorobenzoylchloride were added, and the mixture was stirred for 2 h at room temperature (RT).
Reaction SMILES: FC1C=C(C2N=C(SC)N=C(N3CCOC[C@@H]3C)C=2)C=NC=1.Cl[C:24]1[CH:29]=[C:28]([Cl:30])[N:27]=[C:26]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][C@@H:32]2[CH3:37])[N:25]=1.[CH:38]1([NH:41][C:42](=[O:59])[NH:43][C:44]2[CH:49]=[CH:48][C:47](B3OC(C)(C)C(C)(C)O3)=[CH:46][CH:45]=2)[CH2:40][CH2:39]1>>[Cl:30][C:28]1[N:27]=[C:26]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][C@@H:32]2[CH3:37])[N:25]=[C:24]([C:47]2[CH:48]=[CH:49][C:44]([NH:43][C:42]([NH:41][CH:38]3[CH2:39][CH2:40]3)=[O:59])=[CH:45][CH:46]=2)[CH:29]=1
Reactant: CC1(C)OB(c2ccc(NC(=O)NC3CC3)cc2)OC1(C)C
Reactant: C[C@H]1COCCN1c1nc(Cl)cc(Cl)n1
Agent: CSc1nc(-c2cncc(F)c2)cc(N2CCOC[C@@H]2C)n1
Product: C[C@H]1COCCN1c1nc(Cl)cc(-c2ccc(NC(=O)NC3CC3)cc2)n1
Yield: 31 %

Procedure:
Method as described for intermediate 5 using (S)-4-(4,6-dichloropyrimidin-2-yl)-3-methylmorpholine (intermediate 1B) and 4-(3-cyclopropylureido)phenyl boronic acid pinacol ester to afford an orange solid (400 mg, 31%).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:13]([N:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)=[O:14])=[C:9]([Cl:12])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:20][C:21]1[CH:41]=[CH:40][C:24]2[NH:25][C:26]([C@@H:28]([NH2:39])[CH2:29][CH2:30][CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[N:27][C:23]=2[CH:22]=1.C(N(CC)CC)C>CN(C)C=O>[Cl:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[C:13]([N:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1)=[O:14])[N:5]=[CH:4][N:3]=[C:2]2[NH:39][C@H:28]([C:26]1[NH:25][C:24]2[CH:40]=[CH:41][C:21]([Cl:20])=[CH:22][C:23]=2[N:27]=1)[CH2:29][CH2:30][CH2:31][C:32]([O:34][C:35]([CH3:37])([CH3:36])[CH3:38])=[O:33]
Reactant: CC(C)(C)OC(=O)CCC[C@H](N)c1nc2cc(Cl)ccc2[nH]1
Reactant: O=C(c1cc2ncnc(Cl)c2cc1Cl)N1CCCC1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)CCC[C@H](Nc1ncnc2cc(C(=O)N3CCCC3)c(Cl)cc12)c1nc2cc(Cl)ccc2[nH]1

Procedure:
Prepared analogously to Example 2d from 4,6-dichloro-7-(pyrrolidin-1-yl-carbonyl)-quinazoline, (S)-1-(5-chloro-1H-benzimidazol-2-yl)-4-(tert.-butyloxycarbonyl)-butylamine and triethylamine in N,N-dimethylformamide.
Reaction SMILES: C([O:4][CH2:5][C@@:6]([NH:27]C(=O)C)([CH3:26])[CH2:7][CH2:8][C:9]1[O:10][C:11]([C:14](=[O:25])[CH2:15][CH2:16][CH2:17][O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:12][CH:13]=1)(=O)C.O1CCCC1.CO.[OH2:38].[OH-:39].[Li+]>O>[C:17]([OH:18])(=[O:39])/[CH:16]=[CH:15]/[C:14]([OH:25])=[O:38].[NH2:27][C@:6]([CH3:26])([CH2:7][CH2:8][C:9]1[O:10][C:11]([C:14](=[O:25])[CH2:15][CH2:16][CH2:17][O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:12][CH:13]=1)[CH2:5][OH:4]
Reactant: [OH-]
Reactant: O
Reactant: CC(=O)N[C@](C)(CCc1ccc(C(=O)CCCOc2ccccc2)o1)COC(C)=O
Agent: [Li+]
Solvent: CO
Solvent: C1CCOC1
Product: C[C@](N)(CO)CCc1ccc(C(=O)CCCOc2ccccc2)o1
Product: O=C(O)/C=C/C(=O)O
Temperature: 50 °C
Reaction time: 4 h
Yield: 53.3 %

Procedure:
To a solution of (2R)-1-acetoxy-2-acetylamino-2-methyl-4-[5-(4-phenyloxybutanoyl)furan-2-yl]butane (0.2031 g, 0.49 mmol) obtained in Example (21a) in a mixed solvent of tetrahydrofuran (1.0 ml) and methanol (1.0 ml) were added successively water (1.0 ml) and lithium hydroxide monohydrate (0.2065 g, 4.92 mmol), and the resulting mixture was stirred at 50° C. for 4 hours. After cooling, water was added to the reaction mixture, and the resulting mixture was extracted with dichloromethane. The extract was washed with saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. After filtration, the solvent was removed in vacuo, and the residue was purified by chromatography on a basic silica gel column (NH type) using a mixed solvent of dichloromethane and methanol (100:1) as the eluent to afford the crude (2R)-2-amino-2-methyl-4-[5-(4-phenyloxybutanoyl)furan-2-yl]butan-1-ol (58.4 mg).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[N:10][CH:11]=[C:12]([N+:15]([O-])=O)[C:13]=2[NH2:14])[CH:5]=[N:6][CH:7]=1>CCO.[Pd]>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[N:10][CH:11]=[C:12]([NH2:15])[C:13]=2[NH2:14])[CH:5]=[N:6][CH:7]=1
Reactant: Nc1c(-c2cncc(F)c2)cncc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCO
Product: Nc1cncc(-c2cncc(F)c2)c1N
Temperature: 25 °C
Reaction time: 8 h
Yield: 100 %

Procedure:
To a solution of 5′-fluoro-5-nitro-3,3′-bipyridin-4-amine (LXXI) (621 mg, 2.65 mmol) in EtOH (18 mL) was added 10% Pd/C (93 mg, 15% by wt). The solution was purged with hydrogen and stirred for overnight at room temperature under hydrogen. The suspension was filtered through Celite and concentrated under vacuum. The crude product was purified through a silica gel column (100% CHCl3→3:97 MeOH[7N NH3]:CHCl3) to produce 5′-fluoro-3,3′-bipyridine-4,5-diamine (LXXII) as an off-white solid (542 mg, 2.65 mmol, 100% yield). 1H NMR (DMSO-d6, 500 MHz) δ ppm 4.78 (brs, 2H), 5.28 (brs, 2H), 7.46 (s, 1H), 7.70 (s, 1H), 7.73-7.76 (m, 1H), 8.44-8.45 (m, 1H), 8.56 (d, J=2.8 Hz, 1H); ESIMS found C10H9FN4 m/z 205 (M+H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:12][CH2:11][CH:10]([N:13]3[CH2:17][CH2:16][CH2:15][CH:14]3[CH3:18])[CH2:9]2)[CH:5]=[CH:4][C:3]=1[NH2:19].[O:20]=[C:21]1[CH2:25][CH2:24][CH2:23][N:22]1[C:26]1[CH:34]=[CH:33][C:29]([C:30](O)=[O:31])=[CH:28][CH:27]=1>>[CH3:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:12][CH2:11][CH:10]([N:13]3[CH2:17][CH2:16][CH2:15][CH:14]3[CH3:18])[CH2:9]2)[CH:5]=[CH:4][C:3]=1[NH:19][C:30](=[O:31])[C:29]1[CH:28]=[CH:27][C:26]([N:22]2[CH2:23][CH2:24][CH2:25][C:21]2=[O:20])=[CH:34][CH:33]=1
Reactant: Cc1cc(N2CCC(N3CCCC3C)C2)ccc1N
Reactant: O=C(O)c1ccc(N2CCCC2=O)cc1
Product: Cc1cc(N2CCC(N3CCCC3C)C2)ccc1NC(=O)c1ccc(N2CCCC2=O)cc1

Procedure:
The title compound was prepared in a manner substantially the same as example 1 by coupling 2-methyl-4-(2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-phenylamine with 4-(2-oxo-pyrrolidin-1-yl)-benzoic acid. MS: 447.5 (M+H).
Reaction SMILES: [C:1](Cl)(Cl)=[O:2].[NH2:5][C:6]1[S:7][C:8]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][C:9]=2[N:10]=1>C(OCC)(=O)C>[CH3:15][C:12]1[CH:13]=[CH:14][C:8]2[S:7][C:6]([N:5]=[C:1]=[O:2])=[N:10][C:9]=2[CH:11]=1
Reactant: Cc1ccc2sc(N)nc2c1
Reactant: O=C(Cl)Cl
Solvent: CCOC(C)=O
Product: Cc1ccc2sc(N=C=O)nc2c1

Procedure:
A saturated solution of phosgene in ethyl acetate (200 ml) is charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux condenser. 2-Amino-5-methylbenzothiazole (0.1 mole) is added with stirring. After the addition is completed, the reaction mixture is heated at reflux for a period of about one hour. After this time the mixture is cooled, and the solid product formed is recovered by filtration. The solid is then dried to yield the desired product 5-methylbenzothiazol-2-yl isocyanate dimer.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([N:13]2[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-])=O)[CH:22]=3)[CH2:15][CH2:14]2)=[C:6]2[C:11]=1[N:10]=[C:9]([CH3:12])[CH:8]=[CH:7]2.[Cl-].[NH4+]>CO.O.[Fe]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:13]2[CH2:14][CH2:15][N:16]([CH2:19][CH2:20][C:21]3[CH:22]=[C:23]([CH:24]=[CH:25][CH:26]=3)[NH2:27])[CH2:17][CH2:18]2)=[C:6]2[C:11]=1[N:10]=[C:9]([CH3:12])[CH:8]=[CH:7]2
Reactant: Cc1ccc2c(N3CCN(CCc4cccc([N+](=O)[O-])c4)CC3)ccc(F)c2n1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CO
Solvent: O
Product: Cc1ccc2c(N3CCN(CCc4cccc(N)c4)CC3)ccc(F)c2n1
Temperature: 25 °C
Yield: 77 %

Procedure:
A solution of 8-fluoro-2-methyl-5-{4-[2-(3-nitrophenyl)ethyl]-1-piperazinyl}quinoline (0.126 g; 1 eq) in methanol (4 mL) was added dropwise to a suspension of iron powder (0.125 g; 7 eq) and ammonium chloride (0.119 g; 7 eq) in water (4 mL). The reactants were heated at reflux for 8 hours, with additional amounts of iron powder (total 0.125 g; 7 eq) and ammonium chloride (0.119 g; 7 eq) added in 3 portions during the reaction. The reaction mixture was cooled to room temperature and filtered using a Millipore filter. The filtrate was concentrated under reduced pressure, diluted with water (5 mL) and a saturated aqueous solution of sodium hydrogen carbonate (2 mL) and extracted into ethyl acetate (3×5 mL). The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure to give the title compound in 77% yield (0.090 g).
Reaction SMILES: [C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1[C:17]([CH3:18])=[C:16]2[C:11]([CH2:12][CH2:13][C@@H:14]([C:19]([CH3:27])([CH3:26])[O:20][SiH2:21][C:22]([CH3:25])([CH3:24])[CH3:23])[O:15]2)=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[CH:29]([Li])([CH2:31]C)[CH3:30].C(Br)C=C>O1CCCC1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1>[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1[C:17]([CH2:18][CH2:31][CH:29]=[CH2:30])=[C:16]2[C:11]([CH2:12][CH2:13][C@@H:14]([C:19]([CH3:27])([CH3:26])[O:20][SiH2:21][C:22]([CH3:25])([CH3:24])[CH3:23])[O:15]2)=[CH:10][CH:9]=1)([CH3:3])([CH3:4])[CH3:2]
Reactant: [Li]C(C)CC
Reactant: Cc1c(NC(=O)OC(C)(C)C)ccc2c1O[C@H](C(C)(C)O[SiH2]C(C)(C)C)CC2
Agent: c1cnc2c(c1)ccc1cccnc12
Solvent: C=CCBr
Solvent: C1CCOC1
Product: C=CCCc1c(NC(=O)OC(C)(C)C)ccc2c1O[C@H](C(C)(C)O[SiH2]C(C)(C)C)CC2
Reaction time: 1.5 h
Yield: 85 %

Procedure:
To a solution of (2S)-[2-(tert-butyl-dimethyl-silanyloxymethyl)-8-methyl-chroman-7-yl]-carbamic acid tert-butyl ester (0.41 g, 1.0 mmole) in anhydrous tetrahydrofuran (20 mL) containing 0.010 g of 1,10-phenanthroline at −40° C. was slowly added 2.4 equivalents of 1.3 M s-butyl lithium. After 1 equivalent of s-butyl lithium had been added, the deep red color of the indicator became apparent. The reaction was allowed to stand for 1.5 hours after which allyl bromide (0.24 g, 2.0 mmole) was added. After an additional 4 hours the reaction was quenched with water (4 mL). The reaction mixture was diluted with ether (250 mL) and washed with saturated aqueous sodium bicarbonate (50 mL). The organic layer was separated and the solvent removed under vacuum. Column chromatography on silica gel (5% ethyl acetate/hexane) afforded 0.38 g (85%) of the title compound as an oil, [M+H]+: 448, [α]25D=+34.0° (c=1.03, THF).
Reaction SMILES: C([NH:9][CH:10]([C:14]1[CH:15]=[CH:16][C:17]2[O:21][CH2:20][CH2:19][C:18]=2[CH:22]=1)[C:11]([OH:13])=[O:12])(=O)C1C=CC=CC=1.[H][H]>CO.O.[Pd]>[NH2:9][CH:10]([C:14]1[CH:15]=[CH:16][C:17]2[O:21][CH2:20][CH2:19][C:18]=2[CH:22]=1)[C:11]([OH:13])=[O:12]
Reactant: O=C(NC(C(=O)O)c1ccc2c(c1)CCO2)c1ccccc1
Reactant: [H][H]
Agent: [Pd]
Solvent: O
Solvent: CO
Product: NC(C(=O)O)c1ccc2c(c1)CCO2
Yield: 60 %

Procedure:
The α-benzamido(2,3-dihydro-5-benzofuranyl)acetic acid (100 mg) is dissolved in 20 ml of methanol and 40 ml of water. Then 20 mg of Pd/C catalyst is added and the mixture subjected to 40 pounds/in2 of hydrogen pressure for 4 hours. The mixture is filtered to remove the solid and the methanol is evaporated to give the title compound in about 60% yield.
Reaction SMILES: [CH3:1][NH:2][C:3]1[C:8]([NH2:9])=[CH:7][CH:6]=[C:5]([C:10]([F:13])([F:12])[F:11])[N:4]=1.[CH2:14]([S:16][C:17]1[CH:25]=[CH:24][CH:23]=[CH:22][C:18]=1[C:19](O)=O)[CH3:15].CCN=C=NCCCN(C)C.N1C=CC=CC=1>O>[CH2:14]([S:16][C:17]1[CH:25]=[CH:24][CH:23]=[CH:22][C:18]=1[C:19]1[N:2]([CH3:1])[C:3]2=[N:4][C:5]([C:10]([F:11])([F:12])[F:13])=[CH:6][CH:7]=[C:8]2[N:9]=1)[CH3:15]
Reactant: CNc1nc(C(F)(F)F)ccc1N
Reactant: CCSc1ccccc1C(=O)O
Agent: CCN=C=NCCCN(C)C
Solvent: O
Solvent: c1ccncc1
Product: CCSc1ccccc1-c1nc2ccc(C(F)(F)F)nc2n1C
Temperature: 25 °C
Yield: 57.8 %

Procedure:
A mixture of N2-methyl-6-trifluoromethylpyridin-2,3-diamine (0.96 g), 2-ethylsulfanylbenzoic acid (1.01 g), WSC (1.06 g), and pyridine (5 ml) was stirred under reflux for hours. Into the reaction mixture cooled to room temperature, water was poured, and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. To the resulting residue, a mixture of tripotassium phosphate (2.65 g) and 1-propanol (10 ml) was added, and stirred under reflux for hours. Into the reaction mixture cooled to room temperature, water was poured, and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to give 0.98 g of 2-(2-ethylsulfanylphenyl)-3-methyl-5-trifluoromethyl-3H-imidazo[4,5-b]pyridine (hereinafter referred to as Present Compound 151).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH2:17])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12](C)[N:11]=1.Cl[C:19]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([I:29])[CH:27]=2)[N:22]=[CH:21][N:20]=1>C(O)(C)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[C:26]([I:29])[CH:27]=3)[N:22]=[CH:21][N:20]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1
Reactant: Clc1ncnc2ccc(I)cc12
Reactant: Cc1cccc(COc2ccc(N)cc2Cl)n1
Solvent: CC(C)O
Product: Cl
Product: Clc1cc(Nc2ncnc3ccc(I)cc23)ccc1OCc1ccccn1
Yield: 85.7 %

Procedure:
500 mg of compound 9.2 (2 mmol) and 580 mg of 4-chloro-6-iodo-quinazoline (2 mmol) were dissolved in isopropanol (10 ml). The reaction mixture was refluxed for 12 hours. The solid product was collected by filtration, washed with cold isopropanol (10 mL) and ether (20 mL), and air dried to afford 450 mg of the clean desired product.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:9]1.[Br:22][C:23]1[N:28]=[C:27]([C:29](O)=[O:30])[CH:26]=[CH:25][C:24]=1[F:32]>>[Br:22][C:23]1[N:28]=[C:27]([C:29]([NH:1][C:2]2[CH:3]=[N:4][CH:5]=[CH:6][C:7]=2[N:8]2[CH2:13][CH2:12][CH2:11][C@H:10]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:18])([CH3:20])[CH3:19])[CH2:9]2)=[O:30])[CH:26]=[CH:25][C:24]=1[F:32]
Reactant: O=C(O)c1ccc(F)c(Br)n1
Reactant: CC(C)(C)OC(=O)N[C@H]1CCCN(c2ccncc2N)C1
Product: CC(C)(C)OC(=O)N[C@H]1CCCN(c2ccncc2NC(=O)c2ccc(F)c(Br)n2)C1

Procedure:
Following Method 11 (Example 305), (S)-tert-butyl 1-(3-aminopyridin-4-yl)piperidin-3-ylcarbamate was coupled to 6-bromo-5-fluoropicolinic acid yielding crude (S)-tert-butyl 1-(3-(6-bromo-5-fluoropicolinamido)pyridin-4-yl)piperidin-3-ylcarbamate (92%) which was used as is. LCMS (m/z): 496.2 (MH+); LC Rt=2.90 min.
Reaction SMILES: [OH:1][CH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]2[C@H:9]3[C@H:19]([CH2:20][CH2:21][C@:4]12[CH3:5])[C@:17]1([CH3:18])[C:12](=[CH:13][CH:14]([OH:22])[CH2:15][CH2:16]1)[CH2:11][CH2:10]3>ClC(Cl)Cl.[O-2].[O-2].[Mn+4]>[O:22]=[C:14]1[CH2:15][CH2:16][C@@:17]2([CH3:18])[C:12]([CH2:11][CH2:10][C@@H:9]3[C@@H:19]2[CH2:20][CH2:21][C@@:4]2([CH3:5])[C@H:6]3[CH2:7][CH2:8][C@@H:3]2[CH2:2][OH:1])=[CH:13]1
Reactant: C[C@]12CC[C@H]3[C@@H](CCC4=CC(O)CC[C@@]43C)[C@@H]1CC[C@@H]2CO
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClC(Cl)Cl
Product: C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@]43C)[C@@H]1CC[C@@H]2CO
Yield: 96.6 %

Procedure:
A solution of 17β-(hydroxymethyl) -androst-4-ene 3 ol (27 g, 0.089 mol) in 1200 ml trichloromethane was treated with activated manganese dioxide (66 g). After 3 hours the mixture was filtered. Concentration afforded 26 g (96%) of 3-oxo-17β-(hydroxymethyl)-4 androstene (m.p. 151° C.).