Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([NH:4][C@H:5]([C:10]([OH:12])=[O:11])[CH2:6][CH:7]([CH3:9])[CH3:8])(=O)C.C(N[C@H](C(O)=O)[C@H](CC)C)(=O)C.[OH-].[Na+]>O>[NH2:4][C@H:5]([C:10]([OH:12])=[O:11])[CH2:6][CH:7]([CH3:9])[CH3:8]
Reactant: CC(=O)N[C@@H](CC(C)C)C(=O)O
Agent: CC[C@H](C)[C@H](NC(C)=O)C(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(C)C[C@H](N)C(=O)O
Temperature: 36 °C
Reaction time: 6 h

Procedure:
86.6 grams of this mixture of equal parts of N-acetyl-leucine and N-acetyl-isoleucine were suspended in 400 ml of water and adjusted to pH 7.0 with 50% aqueous sodium hydroxide. There were added 50 mg of CoCl2X6H2O and 50 mg of commerical pig kidney acylase (1200 U/mg) and the mixture was filled up to 500 ml with water. The clear solution was stirred at 36° C. for 6 hours. By filtering with suction, washing and drying there were obtained 17.9 grams of pure L-leucine having a rotary value of [α]D25 =+15.9°.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:9]2[C:14]=1[CH:13]=[CH:12][C:11]([Cl:15])=[CH:10]2)=[O:5])[CH3:2].[CH2:22]([O:29][C:30]([NH:32][CH2:33][CH2:34]Br)=[O:31])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:34][CH2:33][NH:32][C:30]([O:29][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:31])[C:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:9]2[C:14]=1[CH:13]=[CH:12][C:11]([Cl:15])=[CH:10]2)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1[nH]c(-c2ccccc2)c2cc(Cl)ccc12
Reactant: O=C(NCCBr)OCc1ccccc1
Product: CCOC(=O)c1c2ccc(Cl)cc2c(-c2ccccc2)n1CCNC(=O)OCc1ccccc1

Procedure:
15.0 G. of 5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester are reacted with 25.8 g. of 2-[(benzyloxycarbonyl)amino]ethyl bromide in a manner analogous to that described in Example 14. Thereafter, there is obtained an oily crude product, which is chromatographed on 250 g. of silica gel with methylene chloride/ethyl acetate (4:1) as the eluant. From the uniform fractions there is obtained 2-{2-[(benzyloxycarbonyl)amino]ethyl}-5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester; melting point 102°-104° C. Recrystallization from ethanol increases the melting point to 104°-105° C.
Reaction SMILES: C(O)(=O)C.O.[Br:6][C:7]1[C:8]([N+:18]([O-])=O)=[CH:9][C:10]([Cl:17])=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=1.C(OCC)(=O)C>O1CCOCC1>[Br:6][C:7]1[CH:12]=[C:11]([C:13]([F:14])([F:16])[F:15])[C:10]([Cl:17])=[CH:9][C:8]=1[NH2:18]
Reactant: O=[N+]([O-])c1cc(Cl)c(C(F)(F)F)cc1Br
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: Nc1cc(Cl)c(C(F)(F)F)cc1Br
Temperature: 60 °C
Yield: 107.2 %

Procedure:
A mixture of reduced iron (17.7 g), acetic acid (290 ml) and water (145 ml) was stirred with heating at 60° C. for 15 min, 5-bromo-2-chloro-4-nitrobenzotrifluoride (17.7 g) dissolved in 1,4-dioxane (100 ml) was added thereto, and the mixture was stirred with heating at 60° C. for 30 min. The reaction mixture was ice-cooled, ethyl acetate (700 ml) was added and the mixture was stirred at room temperature, The reaction mixture was filtered through a celite (trademark) filter. The filtrate was washed three times with a 1N aqueous sodium hydroxide solution and then with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give 2-bromo-5-chloro-4-(trifluoromethyl)aniline (17.1 g, yield 100%).
Reaction SMILES: [Cl:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[C:4]([Cl:11])[C:3]=1[S:12](Cl)(=[O:14])=[O:13].[NH2:16][CH2:17][CH2:18][NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23]>>[C:22]([O:21][C:20]([NH:19][CH2:18][CH2:17][NH:16][S:12]([C:3]1[C:4]([Cl:11])=[CH:5][CH:6]=[C:7]([N+:8]([O-:10])=[O:9])[C:2]=1[Cl:1])(=[O:14])=[O:13])=[O:26])([CH3:25])([CH3:24])[CH3:23]
Reactant: O=[N+]([O-])c1ccc(Cl)c(S(=O)(=O)Cl)c1Cl
Reactant: CC(C)(C)OC(=O)NCCN
Product: CC(C)(C)OC(=O)NCCNS(=O)(=O)c1c(Cl)ccc([N+](=O)[O-])c1Cl
Yield: 90.5 %

Procedure:
Following the general procedure for sulfonamide formation outlined in example 15, 2,6-dichloro-3-nitrobenzenesulfonyl chloride (1.0 g, 3.44 mmol), t-butyl N-(2-aminoethyl)carbamate (0.5 g, 3.44 mmol) and triethylanine(0.72 mL, 5.16 mmol) were reacted to form the desired product (1.29 g, 90%). 1H NMR (MeOD-d4): δ 7.93 (d, 1H), 7.78 (d, 1H), 3.12 (m, 4H), 1.41 (s, 9H).
Reaction SMILES: [CH2:1]([C:3]1[O:7][CH:6]=[N:5][CH:4]=1)[CH3:2].[CH2:8]([O:10][C:11](=[O:32])[N:12]([C:21]1[CH:26]=[C:25](Br)[N:24]=[C:23]([NH2:28])[C:22]=1[N+:29]([O-:31])=[O:30])[CH2:13][C:14]1[CH:15]=[N:16][C:17]([CH3:20])=[CH:18][CH:19]=1)[CH3:9]>>[CH2:8]([O:10][C:11](=[O:32])[N:12]([C:21]1[CH:26]=[C:25]([C:6]2[O:7][C:3]([CH2:1][CH3:2])=[CH:4][N:5]=2)[N:24]=[C:23]([NH2:28])[C:22]=1[N+:29]([O-:31])=[O:30])[CH2:13][C:14]1[CH:15]=[N:16][C:17]([CH3:20])=[CH:18][CH:19]=1)[CH3:9]
Reactant: CCOC(=O)N(Cc1ccc(C)nc1)c1cc(Br)nc(N)c1[N+](=O)[O-]
Reactant: CCc1cnco1
Product: CCOC(=O)N(Cc1ccc(C)nc1)c1cc(-c2ncc(CC)o2)nc(N)c1[N+](=O)[O-]

Procedure:
The title compound was prepared following the example in preparation 70, using 5-ethyl-oxazole (47 mg) and (2-amino-6-bromo-3-nitro-pyridin-4-yl)-(6-methyl-pyridin-3-ylmethyl)-carbamic acid ethyl ester (100 mg), giving the product (79 mg) as a yellow gum.
Reaction SMILES: [N:1]([CH:4]1[CH2:8][O:7][CH:6]2[CH:9]([O:12][CH3:13])[CH2:10][O:11][CH:5]12)=[N+]=[N-]>CO.[Pd]>[CH3:13][O:12][CH:9]1[CH:6]2[O:7][CH2:8][CH:4]([NH2:1])[CH:5]2[O:11][CH2:10]1
Reactant: COC1COC2C(N=[N+]=[N-])COC12
Agent: [Pd]
Solvent: CO
Product: COC1COC2C(N)COC12
Temperature: 25 °C
Reaction time: 8 h
Yield: 51.9 %

Procedure:
To a solution of 3-azido-6-methoxyhexahydrofuro[3,2-b]furan (0.85 g, 4.6 mmol) in MeOH (50 mL) was added Pd/C (10%, 94.5 mg). The reaction was stirred at rt overnight in 1 atm H2 atmosphere, then the mixture was filtered, and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (DCM/MeOH (0.02 M NH3) (v/v)=25/1) to give the title compound as colorless oil (380 mg, 52.1%).
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]2=[O:22])[CH2:4][CH2:3]1.[O:23]1[C:28]2[CH:29]=[CH:30][C:31]([CH:33]=O)=[CH:32][C:27]=2[O:26][CH:25]=[CH:24]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(O)(=O)C.C(Cl)(Cl)Cl>[O:23]1[C:28]2[CH:29]=[CH:30][C:31]([CH2:33][NH:1][CH:2]3[CH2:3][CH2:4][N:5]([CH2:8][CH2:9][N:10]4[C:19]5[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=5)[N:13]=[CH:12][C:11]4=[O:22])[CH2:6][CH2:7]3)=[CH:32][C:27]=2[O:26][CH:25]=[CH:24]1
Reactant: O=Cc1ccc2c(c1)OC=CO2
Reactant: COc1ccc2ncc(=O)n(CCN3CCC(N)CC3)c2c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClC(Cl)Cl
Product: COc1ccc2ncc(=O)n(CCN3CCC(NCc4ccc5c(c4)OC=CO5)CC3)c2c1
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 10.6 %

Procedure:
To 15 mL of a chloroform solution containing 141 mg of 1-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one and 68 mg of 1,4-benzodioxine-6-carbaldehyde, 28 mg of acetic acid was added and stirred at room temperature for 4.5 hours. To the reaction mixture, 148 mg of sodium triacetoxyborohydride was added and stirred for 1 hour. Aqueous saturated sodium hydrogen carbonate solution was added and the organic layer was separated. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [Silica Gel; Kanto Chemical Co., Inc., Silica Gel 60, eluent; chloroform:methanol=10:1], to give 20 mg of 1-(2-(4-((1,4-benzodioxin-6-ylmethyl)amino)piperidin-1-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one as a brown oil.
Reaction SMILES: [Br-].[C:2]1([CH2:8][CH2:9][CH2:10][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[Br:35][C:36]1[CH:41]=[CH:40][C:39]([C:42]2[O:46][N:45]=[C:44]([CH3:47])[C:43]=2[CH:48]=O)=[CH:38][CH:37]=1>C1COCC1.Cl>[Br:35][C:36]1[CH:37]=[CH:38][C:39]([C:42]2[O:46][N:45]=[C:44]([CH3:47])[C:43]=2[CH:48]=[CH:10][CH2:9][CH2:8][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:40][CH:41]=1
Reactant: c1ccc(CCC[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Reactant: Cc1noc(-c2ccc(Br)cc2)c1C=O
Agent: Cl
Agent: [Br-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: Cc1noc(-c2ccc(Br)cc2)c1C=CCCc1ccccc1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
To a solution of (3-phenylpropyl)triphenylphosphonium bromide (0.956 g, 2.07 mmol) in THF (5 mL) at −78° C. was slowly added n-butyllithium (2.5 M in hexanes, 0.83 mL, 2.07 mmol) and the mixture was stirred for 15 minutes. 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carbaldehyde (0.500 g, 1.88 mmol) in THF (3 mL) was added, and the reaction was warmed to 0° C. and stirred for 1 hour. The solution was diluted with 1 N aqueous HCl and extracted twice with EtOAc. The combined organic layers were dried over Na2SO4, decanted, and concentrated. The residue was purified by silica gel chromatography (0-20% EtOAc in hexanes) to give the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1O)=[C:9]1[O:13][CH2:14][CH2:15][O:16][C:8]1=[CH:7][CH:6]=2.P(Br)(Br)[Br:18].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[Br:18][C:11]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]3[O:16][CH2:15][CH2:14][O:13][C:9]3=2)[N:4]=[CH:3][C:2]=1[Cl:1]
Reactant: Oc1c(Cl)cnc2ccc3c(c12)OCCO3
Reactant: BrP(Br)Br
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Clc1cnc2ccc3c(c2c1Br)OCCO3
Temperature: 25 °C
Yield: 90 %

Procedure:
9-Chloro-2,3-dihydro-[1,4]dioxino[2,3-f]quinolin-10-ol (3.12 g, 13.1 mmol) in dry DMF (16.7 mL) was cooled in ice and phosphorus tribromide (4.78 mL) added drop-wise, and the mixture was stirred, with ice-cooling for 30 minutes then allowed to warm to room temperature and stirred for a further 2 hours. It was cooled in ice and sodium carbonate solution was added and the solid was collected, washed well with water, and dried in vacuo, to afford a pale yellow solid (3.55 g, 90%). LC/MS (ES) m/z 300 (MH+ 100%); 1H-NMR (400 MHz, DMSO), 8.73 (1H, s, CHNHC), 7.62 (1H, d, J=9.12, CHCOCH2), 7.47 (1H, d, J=9.08, CHCN), 4.43 (4H, m, 2×(CH2O)).