Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[NH2:19][CH:20]1[CH2:25][CH2:24][CH2:23][N:22]([C:26]2[CH:27]=[C:28]([CH:33]=[CH:34][CH:35]=2)[C:29]([O:31][CH3:32])=[O:30])[CH2:21]1.[Cl:36][C:37]1[CH:42]=[CH:41][C:40]([C:43]2[S:44][C:45]([CH:49]=O)=[C:46]([CH3:48])[N:47]=2)=[CH:39][CH:38]=1.C(=O)(O)[O-].[Na+]>O1CCCC1>[Cl:36][C:37]1[CH:38]=[CH:39][C:40]([C:43]2[S:44][C:45]([CH2:49][NH:19][CH:20]3[CH2:25][CH2:24][CH2:23][N:22]([C:26]4[CH:27]=[C:28]([CH:33]=[CH:34][CH:35]=4)[C:29]([O:31][CH3:32])=[O:30])[CH2:21]3)=[C:46]([CH3:48])[N:47]=2)=[CH:41][CH:42]=1
Reactant: Cc1nc(-c2ccc(Cl)cc2)sc1C=O
Reactant: COC(=O)c1cccc(N2CCCC(N)C2)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: COC(=O)c1cccc(N2CCCC(NCc3sc(-c4ccc(Cl)cc4)nc3C)C2)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 38.7 %

Procedure:
Acetic acid (0.0251 mL, 0.438 mmol) and sodium triacetoxyborohydride (97.7 mg, 0.438 mmol) were added to methyl 3-(3-aminopiperidin-1-yl)benzoate (79.0 mg, 0.337 mmol) and 2-(4-chlorophenyl)-4-methylthiazole-5-carboaldehyde (80.1 mg, 0.337 mmol) in tetrahydrofuran (5 mL). The reaction mixture was stirred at room temperature for 16 hours. Subsequently, a saturated aqueous sodium bicarbonate solution was added to make the mixture basic. The mixture was then extracted with ethyl acetate and the extract washed with brine, followed by drying over magnesium sulfate and evaporation of the solvent. Purification of the resulting residue by silica gel column chromatography (Chromatorex NH-DM2035 (Fuji Sylysia Chemical Co., Ltd.) hexane:ethyl acetate=5:1->2:1) gave 59.4 mg (39%) of the desired compound as a colorless oil.
Reaction SMILES: C([O:3][C:4](=[O:20])[C:5]([N:8]([CH:10]1[CH2:15][CH2:14][N:13]([S:16]([CH3:19])(=[O:18])=[O:17])[CH2:12][CH2:11]1)[CH3:9])([CH3:7])[CH3:6])C.[OH-].[Na+]>CCO>[CH3:19][S:16]([N:13]1[CH2:14][CH2:15][CH:10]([N:8]([CH3:9])[C:5]([CH3:6])([CH3:7])[C:4]([OH:20])=[O:3])[CH2:11][CH2:12]1)(=[O:18])=[O:17]
Reactant: CCOC(=O)C(C)(C)N(C)C1CCN(S(C)(=O)=O)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CN(C1CCN(S(C)(=O)=O)CC1)C(C)(C)C(=O)O
Yield: 37.7 %

Procedure:
0.76 g (2.48 mmol) of 2-[(1-methanesulfonyl-piperidin-4-yl)-methyl-amino]-2-methyl-propionic acid ethyl ester are dissolved in EtOH (14.3 mL) and 3.72 mL (14.9 mmol) 4 N NaOH are added at RT. The reaction is refluxed for 16 h. The solvent is removed under reduced pressure, the residue is diluted with water and neutralized to pH 7 and lyophilized. The product is dissolved in acetone and filtered. The solvent is removed under reduced pressure to afford 0.26 g of 2-[(1-methanesulfonyl-piperidin-4-yl)-methyl-amino]-2-methyl-propionic acid. Yield: 37%; ESI-MS: 279 [M+H]+; HPLC (Rt): 0.23 min (method D)
Reaction SMILES: [CH:1]([O:4][P:5]([O:22][CH:23]([CH3:25])[CH3:24])([CH:7]([P:12]([O:18][CH:19]([CH3:21])[CH3:20])([O:14][CH:15]([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:9][CH2:10][OH:11])=[O:6])([CH3:3])[CH3:2].S(=O)(=O)(O)[OH:27].C(O)(C)C.C(=O)([O-])O.[Na+]>CC(C)=O.O.[O-2].[O-2].[O-2].[Cr+6]>[CH:15]([O:14][P:12]([O:18][CH:19]([CH3:21])[CH3:20])([CH:7]([P:5]([O:22][CH:23]([CH3:25])[CH3:24])([O:4][CH:1]([CH3:3])[CH3:2])=[O:6])[CH2:8][CH2:9][C:10]([OH:27])=[O:11])=[O:13])([CH3:16])[CH3:17]
Reactant: CC(C)OP(=O)(OC(C)C)C(CCCO)P(=O)(OC(C)C)OC(C)C
Reactant: O=S(=O)(O)O
Agent: [Cr+6]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)=O
Solvent: CC(C)O
Solvent: O
Product: CC(C)OP(=O)(OC(C)C)C(CCC(=O)O)P(=O)(OC(C)C)OC(C)C
Temperature: 2.5 °C
Reaction time: 2 h
Yield: 64 %

Procedure:
Under a nitrogen atmosphere, 4,4-bis(diisopropoxyphosphinoyl)-1-butanol (10.12 g) was dissolved in acetone (30 ml), and the resulting solution was cooled to 0-5° C. A solution of chromium trioxide (2.7 g) and concentrated sulfuric acid (2.3 ml) in water (8 ml) was added dropwise thereto, and the resulting mixture was stirred at 0-5° C. for 2 hours. The mixture was stirred at room temperature for another 10 hours, and then isopropanol (15 ml) was added dropwise thereto and stirred for 30 minutes. The resulting mixture was neutralized with a saturated aqueous sodium hydrogencarbonate solution and the insoluble materials were removed by filtration through Celite. The filtrate was acidified with hydrochloric acid and extracted three times with chloroform, and the organic layer was washed with water and then a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain 4,4-bis(diisopropoxyphosphinoyl)butyric acid (6.75 g, yield 64%).
Reaction SMILES: Br[CH:2]1[CH2:11][CH2:10][C:9]2[C:8]([O:12][CH2:13][C:14]([O:16]CC)=[O:15])=[CH:7][CH:6]=[CH:5][C:4]=2[C:3]1=O.[C:20]1([CH:26]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[NH:27][C:28]([NH2:30])=[S:29])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(N(CC)CC)C.[OH-].[Na+]>O.O1CCCC1.CO.C(O)C>[C:20]1([CH:26]([NH:27][C:28]2[S:29][C:2]3[CH2:11][CH2:10][C:9]4[C:4](=[CH:5][CH:6]=[CH:7][C:8]=4[O:12][CH2:13][C:14]([OH:16])=[O:15])[C:3]=3[N:30]=2)[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: CCOC(=O)COc1cccc2c1CCC(Br)C2=O
Reactant: NC(=S)NC(c1ccccc1)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: CCO
Product: O=C(O)COc1cccc2c1CCc1sc(NC(c3ccccc3)c3ccccc3)nc1-2
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 33 %

Procedure:
To a mixture of ethyl [(6-bromo-5,6,7,8-tetrahydro-5-oxo-1-naphthalenyl)oxy]acetate (1.10 g, 3.36 mmol), N-(diphenylmethyl)thiourea (900 mg, 3.70 mmol), and ethanol (15 mL) was added triethylamine (0.51 mL, 3.70 mmol), and the mixture was refluxed for 6 hours. After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with 1N-hydrochloric acid, saturated aqueous sodium chloride solution, and water, dried over MgSO4, and filtered. The filtrate was concentrated under reduced pressure. To a solution of this concentration residue (0.79 g, 1.70 mmol) in tetrahydrofuran (16 mL)-methanol (4 mL) was added 1N-aqueous sodium hydroxide solution (2.0 mL) dropwise and the mixture was stirred at room temperature for 10 minutes. The solvent was then distilled off under reduced pressure and the residue was recrystallized from acetic acid-water to provide 0.49 g of the title compound. Yield 33%.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[CH2:10][CH2:11][OH:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:16][C:17]1[C:26]2[C:21](=[CH:22][C:23](O)=[CH:24][CH:25]=2)[CH:20]=[CH:19][N:18]=1>ClCCl.CO>[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[CH2:10][CH2:11][O:12][C:23]1[CH:22]=[C:21]2[C:26](=[CH:25][CH:24]=1)[C:17]([NH2:16])=[N:18][CH:19]=[CH:20]2)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: Nc1nccc2cc(O)ccc12
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1CCO
Solvent: CO
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC[C@H]1CCOc1ccc2c(N)nccc2c1

Procedure:
This compound was prepared from N-tert-butoxycarbonyl-L-β-homoprolinol [Leyendecker, F.; Jesser, F.; Laucher, D.; Tetrahedron Lett. 1983, 24, 3513-3516; 590 mg, 2.75 mmol] and 1-amino-6-hydroxy-isoquinoline (1e, 320 mg, 2.0 mmol) by the Mitsunobu procedure described in Example 1f. Yield: 650 mg (91%). ESI-MS: 358.0 (M+H)+. Rf (silica gel; dichloromethane/methanol, 9:1, v/v): 0.37.
Reaction SMILES: [H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[CH3:14][C:15]1[CH:16]=[C:17]([C:20]([N+:23]([O-:25])=[O:24])=[CH:21][CH:22]=1)[CH:18]=[CH2:19].Cl>CN(C=O)C>[CH3:14][C:15]1[CH:16]=[C:17]([CH2:18][CH2:19][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]([O:11][CH2:12][CH3:13])=[O:10])[C:20]([N+:23]([O-:25])=[O:24])=[CH:21][CH:22]=1
Reactant: CCOC(=O)CC(=O)OCC
Reactant: C=Cc1cc(C)ccc1[N+](=O)[O-]
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)C(CCc1cc(C)ccc1[N+](=O)[O-])C(=O)OCC
Temperature: 60 °C
Yield: 28.4 %

Procedure:
To a suspension of 60% sodium hydride (1.36 g, 34 mmol) in DMF (35 mL) was added diethyl malonate (7.00 g, 43.7 mmol). The mixture was heated at 60° C. for 1.5 h, allowed to cool at room temperature and 3-methyl-6-nitrostyrene (4.80 g, 29.4 mmol) in DMF (10 mL) was added dropwise. The mixture was again heated at 4°~50° C. for 4 h, poured into 0.1N hydrochloric acid, and extracted with a 1:1 toluene/ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography with 10:1 hexane/ethyl acetate to give 2.70 g of the title compound (28%).
Reaction SMILES: C([O:4][CH2:5][C:6]1[N:28]([CH3:29])[C:9]2=[N:10][C:11]([O:14][C:15]3[CH:20]=[C:19]([CH3:21])[C:18]([O:22][C:23](=[O:25])[CH3:24])=[C:17]([CH3:26])[C:16]=3[CH3:27])=[CH:12][CH:13]=[C:8]2[N:7]=1)(=O)C.C[O-].[Na+].O>CO>[C:23]([O:22][C:18]1[C:19]([CH3:21])=[CH:20][C:15]([O:14][C:11]2[N:10]=[C:9]3[N:28]([CH3:29])[C:6]([CH2:5][OH:4])=[N:7][C:8]3=[CH:13][CH:12]=2)=[C:16]([CH3:27])[C:17]=1[CH3:26])(=[O:25])[CH3:24]
Reactant: CC(=O)OCc1nc2ccc(Oc3cc(C)c(OC(C)=O)c(C)c3C)nc2n1C
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CC(=O)Oc1c(C)cc(Oc2ccc3nc(CO)n(C)c3n2)c(C)c1C
Reaction time: 1 h
Yield: 88.2 %

Procedure:
To 500 ml of a solution of 26.0 g of 2-acetoxymethyl-5-(4-acetoxy-2,3,5-trimethylphenoxy)-3-methyl-3H-imidazo[4,5-b]pyridine in methanol, a 1.2 ml solution (28%) of sodium methoxide in methanol was added dropwise at −18° C., followed by stirring at the same temperature for one hour. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The extract was washed with saturated saline and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was crystallized from ethanol. The crystals were collected by filtration, whereby 20.5 g of the title compound were obtained.
Reaction SMILES: Cl[C:2]1[C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:15])[CH:8]=2)[N:3]=1.[NH2:16][CH:17]([CH:21]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:22]([OH:24])=[O:23])[C:18]([OH:20])=[O:19]>>[C:12]([C:11]1[C:2]([NH:16][CH:17]([CH:21]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:22]([OH:24])=[O:23])[C:18]([OH:20])=[O:19])=[N:3][C:4]2[C:9]([CH:10]=1)=[CH:8][C:7]([Cl:15])=[CH:6][CH:5]=2)([OH:14])=[O:13]
Reactant: NC(C(=O)O)C(C(=O)O)c1ccccc1
Reactant: O=C(O)c1cc2cc(Cl)ccc2nc1Cl
Product: O=C(O)c1cc2cc(Cl)ccc2nc1NC(C(=O)O)C(C(=O)O)c1ccccc1

Procedure:
In close analogy to the procedure described in Example 32, 2,6-dichloroquinoline-3-carboxylic acid is reacted with 2-amino-3-phenyl-succinic acid [J. Med. Chem. 1973, 16, 1277-1280] to provide the title compound in moderate yield.
Reaction SMILES: [CH3:1][C:2](=[CH:4][CH2:5][CH2:6][CH:7]([CH2:9][CH:10]=[O:11])[CH3:8])[CH3:3].S(=O)(=O)(O)[OH:13]>>[CH:7]1([CH3:8])[CH2:6][CH2:5][CH:4]([C:2]([OH:13])([CH3:3])[CH3:1])[CH:10]([OH:11])[CH2:9]1
Reactant: CC(C)=CCCC(C)CC=O
Reactant: O=S(=O)(O)O
Product: CC1CCC(C(C)(C)O)C(O)C1

Procedure:
Citronellal is treated with aqueous sulfuric acid solution of 5 weight % (hereinafter referring to wt. %) in concentration at room temperature to cause the ring closure of citronellal. Then, after the reaction product is extracted with ether or toluene, para-menthane-3,8-diol is obtained by distilling the extract under reduced pressures (J. Am. Chem. Soc., 75, 2367 (1953), examined Japanese Patent Publication 3-80138 and U.S. Pat. No. 5,298,250).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:16])[CH2:5][N:6]1[C:10]([Si](C)(C)C)=[C:9]([CH3:15])[N:8]=[N:7]1)[CH3:2].F>C1COCC1.O>[CH2:1]([O:3][C:4](=[O:16])[CH2:5][N:6]1[CH:10]=[C:9]([CH3:15])[N:8]=[N:7]1)[CH3:2]
Reactant: CCOC(=O)Cn1nnc(C)c1[Si](C)(C)C
Agent: F
Solvent: O
Solvent: C1CCOC1
Product: CCOC(=O)Cn1cc(C)nn1
Temperature: 25 °C
Reaction time: 3 h
Yield: 94.2 %

Procedure:
To a solution of 0.77 g (3.2 mmol) of ethyl[4-methyl-5-(trimethylsilyl)-1H-1,2,3-triazole-1-yl]acetate from step A in 2 mL of THF was added 1.3 mL (32 mmol) of a solution of 50% hydrofluoric acid in water. The resulting mixture was stirred at room temperature for 3 h and then evaporated to dryness in vacuo. Next, 5 mL of a 2.0 N ammonia in methanol solution was added and then the mixture was again evaporated to dryness in vacuo. The mixture was dissolved in dichloromethane, filtered and then evaporated in vacuo to afford the title compound as a clear gum (0.51 g. 93%). 1HNMR (500 MHz, CDCl3) δ: 7.5 (s, 1H), 5.05 (s, 2H), 4.23 (m, 2H), 2.30 (s, 3H), 1.30 (m, 3H).
Reaction SMILES: [Na].[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[CH:6]=[CH:5][C:4]=1[OH:10].[N+]([C:14]1[CH:15]=[C:16]([C:24]([O:26][CH3:27])=[O:25])[C:17](=[CH:22][CH:23]=1)[C:18]([O:20][CH3:21])=[O:19])([O-])=O.O>CN(C)C=O>[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[CH:6]=[CH:5][C:4]=1[O:10][C:23]1[CH:22]=[C:17]([C:18]([O:20][CH3:21])=[O:19])[C:16](=[CH:15][CH:14]=1)[C:24]([O:26][CH3:27])=[O:25]
Reactant: COC(=O)c1ccc([N+](=O)[O-])cc1C(=O)OC
Reactant: Oc1ccc(Cl)cc1Cl
Agent: [Na]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(Oc2ccc(Cl)cc2Cl)cc1C(=O)OC
Reaction time: 5 h

Procedure:
2.4 g (0.012 mole) of sodium salt of 2,4-dichlorophenol and 2.4 g (0.010 mole) of dimethyl 4-nitrophthalate are dissolved in dry dimethylformamide and stirred at 130°-150° C. for 5 hours. After cooling, the mixture is poured into cold water, extracted with benzene, successively washed with dilute aqueous caustic soda, dilute hydrochloric acid and water, dried over sodium sulfate and then concentrated to obtain 2.5 g of an oily product. It was purified by column chromatography and there was obtained 1.6 g of the intended compound as a viscous oily product. Yield 45%.
Reaction SMILES: [BH4-].[Na+].[C:3]1([CH:9]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:10](=[O:13])[CH2:11][Br:12])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.CCOCC>[OH-].[Na+].CO>[C:3]1([CH:9]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:10]([OH:13])[CH2:11][Br:12])[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: O=C(CBr)C(c1ccccc1)c1ccccc1
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Solvent: CO
Product: OC(CBr)C(c1ccccc1)c1ccccc1
Reaction time: 1 h
Yield: 33.1 %

Procedure:
Sodium borohydride (1 52 g.) in sodium hydroxide solution (15 ml. 0.02M) was added to 1,1-diphenyl-3-bromo-propan-2-one (12 g.) in methanol (50 ml.), and the solution was stirred for one hour. Isolation through ether in the usual manner afforded 1,1-diphenyl-3-bromo-propan-2-ol (10 4 g. 86%) as an oil.
Reaction SMILES: [CH3:1][CH:2]1[C:7]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[N:14]([CH3:18])[C:13](=[O:19])[CH2:12][C:11]3([CH3:21])[CH3:20])=[N:6][NH:5][C:4](=[O:22])[CH2:3]1.[Na].[CH2:24](Br)[CH2:25][CH2:26][CH3:27]>CN(C)C=O>[CH2:24]([N:5]1[C:4](=[O:22])[CH2:3][CH:2]([CH3:1])[C:7]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[N:14]([CH3:18])[C:13](=[O:19])[CH2:12][C:11]3([CH3:21])[CH3:20])=[N:6]1)[CH2:25][CH2:26][CH3:27]
Reactant: CC1CC(=O)NN=C1c1ccc2c(c1)C(C)(C)CC(=O)N2C
Reactant: CCCCBr
Agent: [Na]
Solvent: CN(C)C=O
Product: CCCCN1N=C(c2ccc3c(c2)C(C)(C)CC(=O)N3C)C(C)CC1=O
Reaction time: 0.5 h
Yield: 73 %

Procedure:
To a mixture of 6 g of 6-(5-methyl-3-oxo-2,3,4,5-tetrahydropyridazin-6-yl)-1,4,4-trimethyl-1,2,3,4-tetrahydroquinolin-2-one and 60 ml of dimethylformamide was added 1.8 g of sodium hdyride. After 30 minutes, 4.6 g of butyl bromide was added to the mixture and the whole mixture was stirred for one hour. After completion of the reaction, the mixture was poured into ice-cold water and the precipitated crystals were filtered off and recrystallized from a mixture of ethanol and water to give 5.2 g of 6-(2-butyl-5-methyl-3-oxo-2,3,4,5-tetrahydropyridazin-6-yl)-1,4,4-trimethyl-1,2,3,4-tetrahydroquinolin-2-one, melting at 137°-139° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]([OH:14])=O)=[C:8]2[CH3:15].[CH3:16][O:17][CH2:18][CH2:19][N:20]([CH3:28])[C:21]1[CH:26]=[CH:25][C:24]([NH2:27])=[CH:23][N:22]=1>>[CH3:16][O:17][CH2:18][CH2:19][N:20]([CH3:28])[C:21]1[N:22]=[CH:23][C:24]([NH:27][C:12]([C:9]2[NH:10][C:11]3[C:7]([C:8]=2[CH3:15])=[CH:6][CH:5]=[CH:4][C:3]=3[O:2][CH3:1])=[O:14])=[CH:25][CH:26]=1
Reactant: COCCN(C)c1ccc(N)cn1
Reactant: COc1cccc2c(C)c(C(=O)O)[nH]c12
Product: COCCN(C)c1ccc(NC(=O)c2[nH]c3c(OC)cccc3c2C)cn1

Procedure:
With a procedure similar to the example above, 7-methoxy-3-methyl-1H-indole-2-carboxylic acid {6-[(2-methoxy-ethyl)-methyl-amino]-pyridin-3-yl}-amide was prepared from 7-methoxy-3-methyl-1H-indole-2-carboxylic acid and N2-(2-methoxy-ethyl)-N2-methyl-pyridine-2,5-diamine. LCMS calcd for C20H24N4O3 (m/e) 368, obsd 369 (M+H).
Reaction SMILES: [CH3:1][C@@H:2]([C:5]([N:7]1[C@H:11]([C:12]([OH:14])=[O:13])[CH2:10][CH2:9][CH2:8]1)=[O:6])[CH2:3][SH:4].C(N(CC)C(C)C)(C)C.[Cl:24][CH2:25][CH2:26][CH2:27][CH2:28][O:29][C:30](Cl)=[O:31]>O.CC#N>[Cl:24][CH2:25][CH2:26][CH2:27][CH2:28][O:29][C:30]([S:4][CH2:3][C@@H:2]([CH3:1])[C:5]([N:7]1[CH2:8][CH2:9][CH2:10][C@H:11]1[C:12]([OH:14])=[O:13])=[O:6])=[O:31]
Reactant: O=C(Cl)OCCCCCl
Reactant: C[C@H](CS)C(=O)N1CCC[C@H]1C(=O)O
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: CC#N
Product: C[C@H](CSC(=O)OCCCCCl)C(=O)N1CCC[C@H]1C(=O)O
Temperature: 0 °C
Reaction time: 4 h
Yield: 104.2 %

Procedure:
Captopril (3.50 g, 0.0161 Mol) and N,N-diisopropyl ethylamine (6.80 ml, 0.039 Mol) were dissolved in H2O/CH3CN (80 ml, 1:1) and the mixture was cooled to 0° C. Then 4-chlorobutylchloroformate (2.70 ml, 0.0198 Mol) was added and the reaction was slowly warmed to room temperature and stirred for 4 h. The mixture was then partitioned between HCl (4%, 100 ml) and EtOAc (100 ml). The organic layer was separated and the aqueous phase was extracted with EtOAc (2×100 ml). The combined organic phases were washed with brine (3×60 ml), dried over sodium sulphate and evaporated under reduced pressure affording 1-[(2S)-3-(4-chlorobutoxycarbonyl)mercapto-2-methyl-1-oxopropyl]-L-proline (5.90 g) as a colourless oil that was used without further purification.
Reaction SMILES: C([Li])CCC.CC1(C)CCCC(C)(C)N1.[Br:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=1.[N:24](/[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[N:25]/[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27]>C1COCC1.O>[Br:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=1[N:24]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[NH:25][C:26]([O:28][C:29]([CH3:30])([CH3:31])[CH3:32])=[O:27]
Reactant: Clc1cccc(Br)c1
Reactant: CC(C)(C)OC(=O)/N=N\C(=O)OC(C)(C)C
Agent: CC1(C)CCCC(C)(C)N1
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NN(C(=O)OC(C)(C)C)c1c(Cl)cccc1Br
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 72.6 %

Procedure:
To a stirred solution of 2.5 M Butyllithium in hexanes (13.79 mL, 34.47 mmol) at −20° C. was added dropwise 2,2,6,6-tetramethylpiperidine (5.82 mL, 34.47 mmol) in THF (30 mL). This was stirred for 30 minutes. This solution was cooled down to −78° C., and a solution of 1-bromo-3-chlorobenzene (6 g, 31.34 mmol) in THF (20 mL) was added dropwise so as to maintain the temperature at <−70° C. After 2 hours (Z)-di-tert-butyl diazene-1,2-dicarboxylate (10.82 g, 47.01 mmol) in THF (30 mL) added dropwise at −78° C. Stirred at this temperature for 2 hours, then allowed to warm to room temperature overnight. Water (150 mL) added. The mixture was extracted with EtOAc (2×300 mL). The extracts were combined, washed with brine (100 mL), dried (MgSO4) and reduced go give a residue which was purified by flash silica chromatography, elution gradient 0-10% EtOAc in hexane. Fractions containing suspected product were combined, and reduced to give di-tert-butyl 1-(2-bromo-6-chlorophenyl)hydrazine-1,2-dicarboxylate (9.59 g, 72.5%) 1H NMR (400 MHz, DMSO) δ 1.30-1.50 (18H, s), 7.28 (1H, m), 7.55 (1H, dd), 7.67 (1H, dd), 9.18 (1H, s). m/z (ES+) (M+Na)+=443; HPLC tR=10.76 min.
Reaction SMILES: [CH2:1]([C:4]1[C:5]([OH:15])=[N:6][C:7]2[C:12]([C:13]=1[OH:14])=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH:2]=[CH2:3].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:35](O)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.C(Cl)Cl.C(OCC)C>[CH2:35]([O:14][C:13]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]=[C:5]([OH:15])[C:4]=1[CH2:1][CH:2]=[CH2:3])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1
Reactant: OCc1ccccc1
Reactant: C=CCc1c(O)nc2ccccc2c1O
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOCC
Solvent: C1CCOC1
Solvent: ClCCl
Product: C=CCc1c(O)nc2ccccc2c1OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a mixture of 3-(prop-2-en-1-yl)quinoline-2,4-diol (4.0 g), triphenylphosphine (6.78 g) and benzyl alcohol (2.27 ml) in THF (240 ml) at 0° C. was added dropwise a THF (12 mL) solution of diisopropylazodicarboxylate (5.02 ml). Upon completion of addition, the mixture was allowed to stir at room temperature for 60 minutes. The reaction mixture was concentrated in vacuo to give a thick oil. Oil dissolved in DCM (20 mL) and solids started to precipitate. The solids were filtered and washed with DCM (10 mL). This provided 2.0 g of the desired product. Purification of the mother liquors using flash chromatography (ISCO, 1-8% acetone/DCM) gave an oil that was a mixture of products. This oil was dissolved in 15 mL of diethyl ether and seeded with the desired product. The mixture was stirred overnight and crystallization occurred. The solids were filtered and washed with ether to provide the desired product (1.06 g) as a white solid for a total of 3.06 g of product. LRMS (ES+) M/Z (M+H)+ 292.1.
Reaction SMILES: [C:1]1([CH:7]([CH3:11])[CH2:8][CH:9]=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])(=O)C.[NH4+].C([BH3-])#[N:18].[Na+].Cl>CO>[C:1]1([CH:7]([CH3:11])[CH2:8][CH2:9][NH2:18])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(CC=O)c1ccccc1
Reactant: [BH3-]C#N
Agent: CC(=O)[O-]
Agent: Cl
Agent: [NH4+]
Solvent: CO
Product: CC(CCN)c1ccccc1
Reaction time: 8 h

Procedure:
A mixture of 3-phenylbutyraldehyde (3 ml, 20.18 mmol), ammonium acetate (15 g, 195 mmol) and sodium cyanoborohydride (900 mg, 14.32 mmol) in methanol (50 ml) was stirred overnight under an argon atmosphere. The reaction was acidified to pH 2 by the addition of conc. HCl. The solvent was evaporated, dichloromethane and water were added, and the aqueous layer was made basic (pH 12) by the addition of solid potassium hydroxide. Extraction (dichloromethane) and concentration gave the title compound as an oil. ES-MS (m/z): 150.2 (M+H)+; 1H NMR (CDCl3): d 7.40-7.17 (m, 5H, Ph), 2.81 (q, 1H, CH), 2.62 (m, 2H, CH2), 1.76 (dq, 2H, CH2), 1.29 (d, 3H, CH3).