Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][S:2]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][O:14][C:15]2[CH:28]=[CH:27][C:18]([CH:19]=[C:20]3[S:24][C:23](=[O:25])[NH:22][C:21]3=[O:26])=[CH:17][CH:16]=2)=[CH:8][CH:7]=1)(=[O:4])=[O:3].C(OC(C1CC(C(OCC)=O)=C(C)NC=1C)=O)C>C1(C)C=CC=CC=1>[CH3:1][S:2]([NH:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:12][CH2:13][O:14][C:15]2[CH:28]=[CH:27][C:18]([CH2:19][CH:20]3[S:24][C:23](=[O:25])[NH:22][C:21]3=[O:26])=[CH:17][CH:16]=2)=[CH:10][CH:11]=1)(=[O:3])=[O:4]
Reactant: CS(=O)(=O)Nc1ccc(CCOc2ccc(C=C3SC(=O)NC3=O)cc2)cc1
Agent: CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1
Solvent: Cc1ccccc1
Product: CS(=O)(=O)Nc1ccc(CCOc2ccc(CC3SC(=O)NC3=O)cc2)cc1
Temperature: 145 °C
Reaction time: 0.75 h
Yield: 29.7 %

Procedure:
0.83 g (2 mmole) 5-(4-[2-(4-methanesulfonylaminophenyl)ethoxy]benzylidene)thiazolidine-2,4-dione and 0.65 g (2.6 mmole) diethyl-1,4-dihydro-2,6-dimethyl-3.5-pyridinedicarboxylate was mixed and heated to 145° C. under vacuum. After 45 minutes at 145° C. the reaction mixture was taken off the heat and toluene was added. The toluene solution was decanted off and the solid residue was purified by chromatography on silica gel using dichloromethane:methanol 95:5 as eluent to give 0.25 g (yield 30%) of the desired product.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]([C:13]1[CH:22]=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=1)=O.O1CCCC1.[CH:28]1([Na])[CH:32]=[CH:31][CH:30]=[CH:29]1.O1CCCC1.Cl>C(OCC)C>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]([C:13]1[CH:22]=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=1)=[C:31]1[CH:30]=[CH:29][CH:28]=[CH:32]1
Reactant: [Na]C1C=CC=C1
Reactant: O=C(c1ccc2ccccc2c1)c1ccc2ccccc2c1
Agent: Cl
Solvent: CCOCC
Solvent: C1CCOC1
Product: C1=CC(=C(c2ccc3ccccc3c2)c2ccc3ccccc3c2)C=C1
Temperature: 25 °C
Reaction time: 65 h

Procedure:
A 200-ml two-necked flask equipped with a magnetic stirrer and a three-way cock was thoroughly purged with nitrogen, and sequentially charged with 1.55 g (5.48 mmol) of di-2-naphthyl ketone produced by the method described in Heterocycles, vol. 40, No. 1, 79-83 (1995) and 40 ml of tetrahydrofuran. Then, 5.50 ml (11.0 mmol) of a 2.0 mol/l cyclopentadienyl sodium/tetrahydrofuran solution was gradually added while cooling the mixture in an ice water bath, and then the mixture was stirred at room temperature for 65 hours under a nitrogen atmosphere. Subsequently, 100 ml of 3 N hydrochloric acid and 100 ml of diethyl ether were gradually added. The two-layered solution thus obtained was transferred to a 300-ml separatory funnel and the funnel was shaken several times. The aqueous layer was then removed. This aqueous layer was subjected to extraction with 30 ml of diethyl ether once, and the extract was combined with the organic layer obtained previously. Subsequently, the organic layer obtained was washed 3 times with 100 ml of water and once with 100 ml of saturated brine, and dried over anhydrous magnesium sulfate for 2 hours. The solids were separated by filtration, and the solvent was distilled off to obtain solids. The solids were purified by separation using silica gel chromatography to obtain a target product (yield 1.21 g (67%)). The target product was identified by 1H-NMR spectroscopy.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:3]=1[S:16][C@@H:17]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=1)[C@@H:18]([OH:22])[C:19](O)=[O:20].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(OCC)(=O)C.CO>CN(C=O)C>[CH2:9]([O:8][C:4]1[C:3]2[S:16][C@@H:17]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[C@@H:18]([OH:22])[C:19](=[O:20])[NH:1][C:2]=2[CH:7]=[CH:6][CH:5]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: COc1ccc([C@H](Sc2c(N)cccc2OCc2ccccc2)[C@@H](O)C(=O)O)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CO
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COc1ccc([C@@H]2Sc3c(cccc3OCc3ccccc3)NC(=O)[C@@H]2O)cc1
Temperature: 22 °C
Reaction time: 16 h

Procedure:
To a solution of 2.11 g (4.96 mmol) of (+/−)-(2S,3S)-3-(2-amino-6-(benzyloxy)phenylthio)-2-hydroxy-3-(4-methoxyphenyl)propanoic acid in 25 mL of DMF was added 1.24 g (6.47 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride and 871 mg (6.45 mmol) of 1-hydroxybenzotriazole. The solution was stirred at 22° C. for 16 hours, and a solution of 7:3 ethyl acetate/methanol was added to the reaction. The organic layer was washed with 1 N HCl (2×) and then with a 1:1 mixture of satd. NaHCO3 and brine (2×). The organic layer was dried (Na2SO4) and evaporated. The residue was purified by flash chromatography on silica gel, eluting first with hexane then gradually increasing to 40% ethyl acetate/hexane to give (+/−)-(2S,3S)-9-(benzyloxy)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydrobenzo[b][1,4]thiazepin-4(5H)-one.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH2:12][C:11]3([N:16]([CH3:17])[CH2:15][CH2:14][CH2:13]3)[CH2:10]2)[C:6]([N+:18]([O-])=O)=[CH:5][C:4]=1[NH:21][C:22]1[N:27]=[C:26]([C:28]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[N:30]([CH3:37])[CH:29]=2)[CH:25]=[CH:24][N:23]=1.[NH4+].[Cl-].C(O)C>[Fe].O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH2:12][C:11]3([N:16]([CH3:17])[CH2:15][CH2:14][CH2:13]3)[CH2:10]2)[C:6]([NH2:18])=[CH:5][C:4]=1[NH:21][C:22]1[N:27]=[C:26]([C:28]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[N:30]([CH3:37])[CH:29]=2)[CH:25]=[CH:24][N:23]=1
Reactant: COc1cc(N2CC3(CCCN3C)C2)c([N+](=O)[O-])cc1Nc1nccc(-c2cn(C)c3ccccc23)n1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: COc1cc(N2CC3(CCCN3C)C2)c(N)cc1Nc1nccc(-c2cn(C)c3ccccc23)n1
Yield: 76.7 %

Procedure:
A mixture of N-[2-Methoxy-4-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 147, 200 mg, 0.40 mmol), iron (134 mg, 2.40 mmol) and NH4Cl (16 mg, 0.30 mmol), ethanol (18 mL) and water (6 mL) was heated at reflux for 1 h then the mixture was allowed to cool. The mixture was then filtered and concentrated in vacuo. The resulting residue was triturated in 10% CH3OH in CH2Cl2 (15 mL) for 15 minutes and the mixture was then filtered. The residues were triturated again with 10% CH3OH in CH2Cl2 (15 mL) and the mixture then filtered. The combined filtrates were washed with brine, dried (Na2SO4) and concentrated in vacuo. Purification by FCC, eluting with 2% 7N methanolic ammonia in CH2Cl2 gave the title compound (144 mg, 77%) as a dark green foam; 1H NMR: 1.66-1.80 (2H, m), 2.06-2.16 (2H, m), 2.42 (3H, s), 2.66 (2H, t), 3.59 (2H, d), 3.75 (3H, s), 3.83-3.91 (5H, m), 4.01 (2H, s), 6.30 (1H, s), 7.09 (1H, d), 7.16 (1H, t), 7.21-7.28 (1H, m), 7.31 (1H, s), 7.51 (1H, d), 7.70 (1H, s), 8.23 (1H, d), 8.26 (1H, s), 8.43 (1H, d); m/z: ES+ MH+ 470.7.
Reaction SMILES: [Cl:1][C:2]1[C:11]([C:12]2([C:15]#[N:16])[CH2:14][CH2:13]2)=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6]C)=[O:5].CO.O.O.[OH-].[Li+]>O1CCCC1>[Cl:1][C:2]1[C:11]([C:12]2([C:15]#[N:16])[CH2:14][CH2:13]2)=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([OH:6])=[O:5]
Reactant: COC(=O)c1cccc(C2(C#N)CC2)c1Cl
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: N#CC1(c2cccc(C(=O)O)c2Cl)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 89.8 %

Procedure:
To a solution of methyl 2-chloro-3-(1-cyanocyclopropyl)benzoate (13.5 g, 57.3 mmol) in tetrahydrofuran (180 mL)/methanol (60 mL)/water (60 mL) was added lithium hydroxide monohydrate (3.62 g, 86.3 mmol), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, and to the obtained residue was dropwise added 6N hydrochloric acid (20 mL). The precipitate was collected by filtration, and washed with water to give the title compound (11.4 g, 90%) as white crystals.
Reaction SMILES: [C:1]1([C:7]2[C:12]([C:13]([OH:15])=O)=[CH:11][N:10]=[C:9]([NH:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:24][NH:25][C@@H:26]([CH3:35])[C@@H:27]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[OH:28]>>[OH:28][CH:27]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH:26]([N:25]([CH3:24])[C:13]([C:12]1[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[N:8][C:9]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[N:10][CH:11]=1)=[O:15])[CH3:35]
Reactant: CN[C@@H](C)[C@H](O)c1ccccc1
Reactant: O=C(O)c1cnc(NCc2ccccn2)nc1-c1ccccc1
Product: CC(C(O)c1ccccc1)N(C)C(=O)c1cnc(NCc2ccccn2)nc1-c1ccccc1
Yield: 61.7 %

Procedure:
Starting from 4-phenyl-2-[(pyridin-2-ylmethyl)amino]pyrimidine-5-carboxylic acid (0.48 g, 1.5 mmol) and (1R,2S)-2-methylamino-1-phenyl-1-propanol [(−)-ephedrine] (0.25 g, 1.5 mmol) according to the method described in Example 17. the title amide 0.42 g (58%) is obtained as white crystalline material; m.p.: 82° C.; [M+H]+ 468.
Reaction SMILES: [CH2:1]([S:8][C:9]1[N:13]=[C:12]([NH:14][CH:15]=O)[N:11]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1CCOCC1.[BH4-].[Na+]>C(O)(=O)C>[CH2:1]([S:8][C:9]1[N:13]=[C:12]([NH:14][CH3:15])[N:11]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=CNc1nc(SCc2ccccc2)nn1-c1ccccc1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: CC(=O)O
Product: CNc1nc(SCc2ccccc2)nn1-c1ccccc1
Temperature: 100 °C
Reaction time: 2 h
Yield: 72.3 %

Procedure:
The product of stage (a) (31 g) was mixed with dioxan (200 ml) and 96% sodium borohydride (19.6 g) at room temperature, and acetic acid (30 ml) was added with vigorous stirring. The mixture was stirred at 100° C. for 2 hours, after which the solvents were removed and the mixture was added carefully to water. The product was then extracted with ethyl acetate and chromatographed on silica gel to give 21.4 g of the desired product.
Reaction SMILES: [CH2:1]([C:5]1[N:6]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[O:28]C)[C:7](/[CH:10]=[C:11](\[CH2:15][C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)/[C:12]([OH:14])=[O:13])=[CH:8][N:9]=1)[CH2:2][CH2:3][CH3:4]>C(Cl)Cl>[CH2:1]([C:5]1[N:6]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[OH:28])[C:7](/[CH:10]=[C:11](\[CH2:15][C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)/[C:12]([OH:14])=[O:13])=[CH:8][N:9]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1ncc(/C=C(\Cc2cccs2)C(=O)O)n1Cc1ccccc1OC
Solvent: ClCCl
Product: CCCCc1ncc(/C=C(\Cc2cccs2)C(=O)O)n1Cc1ccccc1O

Procedure:
The title compound was prepared from the 2-methoxy compound prepared in Example 64 using boron tribromide in methylene chloride; 181°-183° C.
Reaction SMILES: [CH:1]1([Li:6])[CH:5]=[CH:4][CH:3]=[CH:2]1.[C:7]1([N:13]2[CH2:15][CH2:14]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>>[CH:1]1([CH2:15][CH2:14][NH:13][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH:5]=[CH:4][CH:3]=[CH:2]1.[CH:1]1([Li:6])[CH:5]=[CH:4][CH:3]=[CH:2]1
Reactant: c1ccc(N2CC2)cc1
Agent: [Li]C1C=CC=C1
Product: C1=CC(CCNc2ccccc2)C=C1

Procedure:
Reaction of cyclopentadienyllithium II1 with N-phenylaziridine III1 to give N-(2-cyclopentadienylethyl)aniline IV1 ##STR8## 0.36 g (5 mmol) of cyclopentadienyllithium was added in several portions to a solution of 0.6 g (=5 mmol) of N-phenylaziridine in 50 ml of tetrahydrofuran (THF) under an argon atmosphere at -30° C. After the addition was complete, the mixture was stirred at -30° C. for 1 hour and then warmed to room temperature over the course of 12 hours. Then 50 ml of a saturated aqueous NH4Cl solution were added, the mixture was stirred for 1 hour and the organic phase was separated off. The latter was dried over anhydrous Na2SO4 and filtered, and the solvent was removed under oil pump vacuum. 0.83 g (4.5 mmol, 90% of theory) of IV1 was obtained as a yellow oil.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[N:4]=[C:5](F)[C:6]([CH3:12])=[N:7]2.[C:14]([NH2:18])([CH3:17])([CH3:16])[CH3:15]>CS(C)=O.C(Cl)Cl>[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[N:4]=[C:5]([NH:18][C:14]([CH3:17])([CH3:16])[CH3:15])[C:6]([CH3:12])=[N:7]2
Reactant: CC(C)(C)N
Reactant: Cc1nc2cccc(Br)c2nc1F
Solvent: CS(C)=O
Solvent: ClCCl
Product: Cc1nc2cccc(Br)c2nc1NC(C)(C)C

Procedure:
A solution of 5-bromo-3-fluoro-2-methylquinoxaline (Example 126f; 1.05 g, 4.36 mmol) and tert-butylamine (2.29 mL, 21.8 mmol) in DMSO (10 mL) was stirred at 100° C. for 2.5 h. The mixture was then diluted with DCM (150 mL) and washed with saturated aq. NaHCO3 (3×100 mL). The organic layer was separated, dried over MgSO4, filtered, and concentrated. The crude material was adsorbed onto silica and chromatographically purified (silica gel; 0-4% MeOH in DCM) to give 8-bromo-N-(tert-butyl)-3-methylquinoxalin-2-amine as an amorphous pink solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 7.82 (d, J=7.6 Hz, 1H), 7.68-7.74 (m, 1H), 7.22 (t, J=7.9 Hz, 1H), 6.17 (s, 1H), 2.55 (s, 3H), 1.58 (s, 9H). m/z (ESI, +ve ion) 294.0/296.0 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:26])=[C:11]([CH2:13][CH2:14][O:15]S(C3C=CC(C)=CC=3)(=O)=O)[N:12]=2)=[CH:4][CH:3]=1.[CH3:27][O:28][C:29](=[O:40])[CH2:30][CH2:31][C:32]1[CH:37]=[CH:36][C:35](O)=[CH:34][C:33]=1[CH3:39].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C>[CH3:27][O:28][C:29](=[O:40])[CH2:30][CH2:31][C:32]1[CH:37]=[CH:36][C:35]([O:15][CH2:14][CH2:13][C:11]2[N:12]=[C:8]([C:5]3[CH:6]=[N:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[O:9][C:10]=2[CH3:26])=[CH:34][C:33]=1[CH3:39]
Reactant: Cc1ccc(S(=O)(=O)OCCc2nc(-c3ccc(Cl)nc3)oc2C)cc1
Reactant: COC(=O)CCc1ccc(O)cc1C
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)CCc1ccc(OCCc2nc(-c3ccc(Cl)nc3)oc2C)cc1C
Temperature: 60 °C

Procedure:
A mixture of toluene-4-sulfonic acid 2-[2-(6-chloro-pyridin-3-yl)-5-methyl-oxazol-4-yl]-ethyl ester (0.4 g, 1.0 mmol, 3-(4-Hydroxy-2-methyl-phenyl)-propionic acid methyl ester (0.2 g, 1 mmol) and Cs2CO3 (0.49 g, 1.5 mmol) in DMF (5 mL) is heated at 60° C. overnight, cooled to room temperature, diluted with ethyl acetate, washed with water and dried. Column chromatography on silica gel gave the product (85 mg).
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[C:6]([C:12]([NH:14][C:15]2[O:19][C:18]([C:20]([O:22]C)=[O:21])=[CH:17][CH:16]=2)=[O:13])[O:7][C:8]=1[CH:9]([CH3:11])[CH3:10])([CH3:3])[CH3:2].[OH-].[Li+]>>[CH:1]([C:4]1[CH:5]=[C:6]([C:12]([NH:14][C:15]2[O:19][C:18]([C:20]([OH:22])=[O:21])=[CH:17][CH:16]=2)=[O:13])[O:7][C:8]=1[CH:9]([CH3:11])[CH3:10])([CH3:2])[CH3:3]
Reactant: COC(=O)c1ccc(NC(=O)c2cc(C(C)C)c(C(C)C)o2)o1
Agent: [Li+]
Agent: [OH-]
Product: CC(C)c1cc(C(=O)Nc2ccc(C(=O)O)o2)oc1C(C)C
Yield: 74.4 %

Procedure:
This ester (42 mg, 0.132 mmol) was hydrolyzed with lithium hydroxide in a conventional manner, and then the residue was recrystallized to obtain the title compound (35, 30 mg, 75%) as pale yellow prisms.
Reaction SMILES: Br[CH2:2][C:3](=[O:24])[CH:4]=[P:5]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C:25]1([SH:31])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[Na].O>C(O)C>[O:24]=[C:3]([CH2:2][S:31][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH:4]=[P:5]([C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)([C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: Sc1ccccc1
Reactant: O=C(C=P(c1ccccc1)(c1ccccc1)c1ccccc1)CBr
Agent: [Na]
Solvent: CCO
Solvent: O
Product: O=C(C=P(c1ccccc1)(c1ccccc1)c1ccccc1)CSc1ccccc1
Yield: 74.1 %

Procedure:
3-Bromo-2-oxopropylidenetriphenylphosphorane (17.85 g) was added to a solution of thiophenol (5.22 g; 4.86 ml) in anhydrous ethanol (70 ml) containing sodium (1.09 g). The mixture was heated at reflux for 150 minutes and was then poured into a mixture of ice and water (250 ml). The mixture was then extracted with dichloromethane and the extract was washed with dilute aqueous sodium hydroxide solution (2 N) and then with water, and was dried over magnesium sulphate. Evaporation of the solvent gave a residual oil which was triturated with petroleum ether (b.p. 40°-60° C.), and the resulting crude solid was recrystallised from a mixture of toluene and petroleum ether (b.p. 60°-80° C.) to give 2-oxo-3-phenylthiopropylidenetriphenylphosphorane (14.2 g) in the form of cream prisms, m.p. 132°-134° C. [elemental analysis: C, 76.4; H, 5.3; P, 7.3; S, 7.7%. C27H23OPS requires C, 76.0; H, 5.4; P, 7.3; S, 7.5%. νmax 715, 740, 750, 1110, 1385, 1440, 1485 and 1550 cm-1 ].
Reaction SMILES: C[O:2][C:3]([CH:5]1[CH2:9][CH:8]([N:10]2[N:14]=[N:13][C:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[N:11]2)[CH2:7][N:6]1[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:4].[Li+].[OH-]>CO>[C:24]([O:23][C:21]([N:6]1[CH2:7][CH:8]([N:10]2[N:14]=[N:13][C:12]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)=[N:11]2)[CH2:9][CH:5]1[C:3]([OH:4])=[O:2])=[O:22])([CH3:27])([CH3:25])[CH3:26]
Reactant: COC(=O)C1CC(n2nnc(-c3ccccc3)n2)CN1C(=O)OC(C)(C)C
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CC(n2nnc(-c3ccccc3)n2)CC1C(=O)O
Reaction time: 8 h

Procedure:
To a solution of 4-[5-(phenyl)-tetrazol-2-yl]-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (4) in MeOH cooled to 0 degree is LiOH, and the mixture is stirred overnight. After removal of MeOH, the residue is acidified with HCl, extracted with EA, dried and concentrated to give the corresponding 4-[5-(phenyl)-tetrazol-2-yl]-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (5).
Reaction SMILES: O.C(O[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C:13]([CH:15]=[O:16])=[O:14])CCC.[CH3:17][C:18]([NH2:29])([CH3:28])[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1>CS(C)=O>[CH3:28][C:18]([N:29]=[C:15]([O:16][CH2:12][CH2:7][CH2:8][CH3:9])[C:13]([C:8]1[CH:7]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:14])([CH3:17])[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1
Reactant: CCCCOc1ccccc1C(=O)C=O
Reactant: COc1ccc(CC(C)(C)N)cc1
Solvent: CS(C)=O
Solvent: O
Product: CCCCOC(=NC(C)(C)Cc1ccc(OC)cc1)C(=O)c1ccccc1
Temperature: 20 °C
Reaction time: 1 h

Procedure:
632 mg of 2-n-butoxyphenylglyoxal hydrate are dissolved in 0.5 ml of dimethylsulfoxide, and a solution of 440 mg of α,α-dimethyl-4-methoxyphenethylamine in 1.5 ml of dimethylsulfoxide is added thereto. The mixture is stirred at 20° C. for one hour, whereby a solution of α-(α,α-dimethyl-4-methoxyphenethylimino)-2-n-butoxyacetophenone in dimethylsulfoxide is obtained.
Reaction SMILES: [C:1]([N:5]1[C:9]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)=[CH:8][C:7]([CH2:17][CH2:18][CH:19]=O)=[N:6]1)([CH3:4])([CH3:3])[CH3:2].[CH3:21][O:22][C:23]1[CH:28]=[CH:27][C:26]([N:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[CH:25][CH:24]=1.CCN(C(C)C)C(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[C:1]([N:5]1[C:9]([C:10]2[CH:11]=[CH:12][C:13]([Cl:16])=[CH:14][CH:15]=2)=[CH:8][C:7]([CH2:17][CH2:18][CH2:19][N:32]2[CH2:33][CH2:34][N:29]([C:26]3[CH:25]=[CH:24][C:23]([O:22][CH3:21])=[CH:28][CH:27]=3)[CH2:30][CH2:31]2)=[N:6]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)n1nc(CCC=O)cc1-c1ccc(Cl)cc1
Reactant: COc1ccc(N2CCNCC2)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(N2CCN(CCCc3cc(-c4ccc(Cl)cc4)n(C(C)(C)C)n3)CC2)cc1

Procedure:
104 mg (75%) of target compound was obtained by using a method same as in Example 1 by using 3-(1-tert-butyl-5-(4-chlorophenyl)-1H-pyrazol-3-yl)propanal (80 mg, 0.275 mmol), 1-(4-methoxyphenyl)piperazine (53 mg, 0.275 mmol), DIPEA (0.072 mL, 0.413 mmol) and NaBH(OAc)3 (175 mg, 0.825 mmol).
Reaction SMILES: [CH3:1][S:2][C:3]1[C:11]([N+:12]([O-])=O)=[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][N:5]2[N:4]=1>C(O)C.O.C(O)(=O)C.[Zn]>[CH3:1][S:2][C:3]1[C:11]([NH2:12])=[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][N:5]2[N:4]=1
Reactant: CSc1nn2ccccc2c1[N+](=O)[O-]
Agent: [Zn]
Solvent: O
Solvent: CCO
Solvent: CC(=O)O
Product: CSc1nn2ccccc2c1N
Temperature: 80 °C
Reaction time: 0.5 h

Procedure:
To a suspension of 2-methylthio-3-nitropyrazolo[1,5-a]pyridine (Reference; Heterocycles, 1977, 6, 379) (400 mg) in ethanol (20 mL), water (10 mL), acetic acid (2 mL) was added zinc powder (800 mg) and the reaction mixture was heated and stirred for 30 minutes at 80° C. The insoluble residue was filtered out, water was added to the filtrate and extraction was performed with ethyl acetate, and then the organic extract was washed with saturated aqueous sodium bicarbonate and brine. The organic extract was dried over anhydrous magnesium sulfate and filtered, and the solvent was evaporated under reduced pressure to afford (2-methylthiopyrazolo[1,5-a]pyridin-3-yl)amine as a crude product.
Reaction SMILES: [C:1]([N:6]1[C@@:10]2([CH2:14][CH2:13][N:12]([C@@H:15]([C:20]([O:22]CC3C=CC=CC=3)=[O:21])[CH2:16][CH:17]([CH3:19])[CH3:18])[C:11]2=[O:30])[CH2:9][CH2:8][CH2:7]1)(=[O:5])[CH:2]([CH3:4])[CH3:3]>CO>[C:1]([N:6]1[C@@:10]2([CH2:14][CH2:13][N:12]([C@@H:15]([C:20]([OH:22])=[O:21])[CH2:16][CH:17]([CH3:18])[CH3:19])[C:11]2=[O:30])[CH2:9][CH2:8][CH2:7]1)(=[O:5])[CH:2]([CH3:4])[CH3:3]
Reactant: CC(C)C[C@H](C(=O)OCc1ccccc1)N1CC[C@]2(CCCN2C(=O)C(C)C)C1=O
Solvent: CO
Product: CC(C)C[C@H](C(=O)O)N1CC[C@]2(CCCN2C(=O)C(C)C)C1=O
Yield: 96.3 %

Procedure:
A degassed solution of 13 (134 mg, 0.32 mmol) in methanol containing 10% Pd/C (27 mg) was hydrogenated under 16 psi for 24 h. The mixture was filtered through a pad of celite and the filtered solution was concentrated under reduced pressure to afford 16 (100 mg, 95%) as a colourless oil. M.p. 68-69° C. [α]20D −2° (c 1.1, MeOH). 1H-NMR [300 MHz, acetone-d6] δ 0.87-0.91 (2d, J=7, 6H), 1.09-1.12 (2d, 6H), 1.46 (m, 1H), 1.70 (m, 2H), 1.90-2.10 (m, 5H), 2.49 (m, 1H), 2.70 (m, 1H), 3.30 (m, 1H), 3.49 (dt, J1=8, J2=10, 1H), 3.61-3.75 (m, 2H), 4.71 (dd, J1=5, J2=11, 1H). 13C-NMR (75 MHz, CDCl3) δ 16.4, 16.6, 21.1, 23.0, 24.3, 25.0, 30.8, 32.6, 36.6, 36.9, 40.6, 48.0, 53.4, 67.5, 171.8, 174.2, 176.2. ESI-MS Calcd for C17H28N2O4: 324.20. Found: 323.3 (M−1)+.
Reaction SMILES: [CH3:1][C:2]1[NH:10][C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]=1[C:11]([O:13][CH3:14])=[O:12].[H-].[Na+].Br[CH:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH3:19].[Cl-].[NH4+]>CN(C)C=O>[CH3:1][C:2]1[N:10]([CH:18]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH3:19])[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]=1[C:11]([O:13][CH3:14])=[O:12]
Reactant: COC(=O)c1c(C)[nH]c2ncccc12
Reactant: CC(Br)c1ccccc1
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: COC(=O)c1c(C)n(C(C)c2ccccc2)c2ncccc12
Temperature: 25 °C
Yield: 31.7 %

Procedure:
To a cooled (0° C.) solution of methyl 2-methyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylate (1.02 g, 5.36 mmol) in N,N-dimethylformamide (20 mL) was added sodium hydride (60% w/w, 236 mg, 5.90 mmol). The resultant mixture was stirred for 15 minutes. Then (1-bromoethyl)benzene (2.00 g, 10.8 mmol) was added and the reaction was allowed to warm to room temperature. The reaction was maintained at ambient temperature for 12 hours. The reaction mixture was poured into saturated ammonium chloride solution (100 mL) with stirring. The mixture was extracted with ethyl acetate (200 mL×2) and the combined organic phase was washed with brine, dried over magnesium sulfate, filtered, and concentrated to give crude product which was purified by column chromatography (petroleum ether/ethyl acetate=20:1) to afford methyl 2-methyl-1-(1-phenylethyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxylate (500 mg, 31.7%) as a viscous oil. 1H NMR (300 MHz, CD3OD): δ 8.38-8.35 (m, 1H), 8.25-8.23 (m, 1H), 7.30-7.14 (m, 6H), 6.55-6.48 (m, 1H), 3.88 (s, 3H), 2.54 (s, 3H), 2.02 (d, J=7.2 Hz, 3H).