Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C@@:9]([NH2:15])([CH2:11][C:12]([CH3:14])=[CH2:13])[CH3:10])[CH:5]=[CH:6][C:7]=1[F:8].[C:16]([N:24]=[C:25]=[S:26])(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.ClCCl>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([C@@:9]([NH:15][C:25]([NH:24][C:16](=[O:23])[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)=[S:26])([CH2:11][C:12]([CH3:14])=[CH2:13])[CH3:10])[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: O=C(N=C=S)c1ccccc1
Reactant: C=C(C)C[C@](C)(N)c1ccc(F)c(Br)c1
Solvent: C1CCOC1
Solvent: ClCCl
Product: C=C(C)C[C@](C)(NC(=S)NC(=O)c1ccccc1)c1ccc(F)c(Br)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 84 %

Procedure:
To a solution of (S)-2-(3-bromo-4-fluorophenyl)-4-methylpent-4-en-2-amine (1.3 g, 4.6 mmoles, 1.0 equiv) in THF (5 mL) is added benzoyl isothiocyanate (0.63 mL, 4.6 mmoles, 1 equiv). The reaction is stirred at room temperature for 3 h. The solvent is removed under reduced pressure and the residue is purified by silica gel chromatography eluting with a linear gradient of 20% dichloromethane: hexanes to 50% dichloromethane: hexanes to give the title compound (84% yield): MS (m/z): 457, 459 (M+23).
Reaction SMILES: [CH3:1][C:2]1[C:7](=[O:8])[CH2:6][CH:5]([C:9]([CH3:11])=[CH2:10])[CH2:4][CH:3]=1.[OH:12]O.[OH-].[Na+]>CO.O>[C:9]([C@@H:5]1[CH2:6][C@@H:7]2[C@@:2]([CH3:1])([O:8]2)[C:3](=[O:12])[CH2:4]1)([CH3:11])=[CH2:10]
Reactant: OO
Reactant: C=C(C)C1CC=C(C)C(=O)C1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: C=C(C)[C@H]1CC(=O)[C@]2(C)O[C@@H]2C1
Reaction time: 5 h

Procedure:
(R)-Carvone was epoxidized according to a modification of the method of E. Klein and G. Ohloff (Tetrahedron, 1963, 11, 1091-1099). Thus H2O2 (31%, 95 mL, 836 mmol, 1.3 equivalents) was added to a solution of (L)-carvone (100 mL, 640 mmol) in 650 mL of methanol at <5° C. After cooling to <0° C., 6N NaOH (10.5 mL, 63 mmol, 0.1 equivalents) was added. The reaction temperature was maintained at <5° C. After 5 hours, the reaction was diluted with 650 mL water, then quenched with 0.5 N KH2PO4 (250 mL) and 325 mL of 1 molal Na2SO3, keeping the temperature at <25° C. The reaction was extracted with 2×750 mL tert-butyl methyl ether. The combined tert-butyl methyl ether extracts were washed with 500 mL each of 20% aqueous NaCl then 10% then 25% to provide a clear organic layer which was dried over MgSO4, then filtered and concentrated, then chased with 100 mL of methanol. The resulting solution assayed (GC) at 101.3 g (96%) of the titled compound, which contained 5% of the minor isomer. 1H NMR (400 MHz, CDCl3) δ ppm 1.40 (s, 3 H) 1.70 (s, 3 H) 1.89 (ddd, J=14.75, 11.11, 1.17 Hz, 1 H) 2.02 (dd, J=17.56, 11.66 Hz, 1 H) 2.31 -2.41 (m, 1 H) 2.58 (ddd, J=17.56, 4.67, 1.37 Hz, 1 H) 2.65-2.76 (m, 1 H) 3.44 (dd, J=3.09, 1.03 Hz, 1 H) 4.70 (d, J=0.69 Hz, 1 H) 4.75-4.80 (m, 1 H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].[NH2:10][C:11]1[CH:15]=[C:14]([CH3:16])[NH:13][N:12]=1.C[N:18](C=O)C>O>[F:1][C:2]1[CH:3]=[C:4]([NH:5][N:18]=[C:15]2[C:14]([CH3:16])=[N:13][N:12]=[C:11]2[NH2:10])[CH:6]=[CH:7][C:8]=1[F:9]
Reactant: Nc1ccc(F)c(F)c1
Reactant: CN(C)C=O
Reactant: Cc1cc(N)n[nH]1
Solvent: O
Product: CC1=NN=C(N)C1=NNc1ccc(F)c(F)c1

Procedure:
4-[(3,4-difluorophenyl)hydrazono]-5-methyl-4H-pyrazol-3-ylamine was prepared from 3,4-difluoroaniline (0.62 g, 4.8 mmol) and 3-amino-5-methylpyrazole (0.6 g, 6.2 mmol) according to procedure described above except that the substituted aniline was initially dissolved in a mixture of water (7.2 mL) and DMF (2.0 mL) prior to being acidified. The crude material was initially purified by column chromatography (CH2Cl2:MeOH=20:1). The isolated material was further purified by recrystallization from ethyl acetate/hexanes to yield 0.2 g (18%) of the compound as a yellow solid. MS (m/z, ES+): 238.1 (M+1, 100%).
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[CH2:9][N:8]([CH2:10][CH2:11][OH:12])[CH2:7][N:6]([CH2:13][CH2:14][OH:15])[CH2:5]1.[OH-].[K+].[C:18](OC)(=[O:36])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]/[CH:26]=[CH:27]\[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35].C(O)(=O)CCCCCCC/C=C\CCCCCCCC>CO.C(Cl)Cl>[C:18]([O:12][CH2:11][CH2:10][N:8]1[CH2:9][N:4]([CH2:3][CH2:2][OH:1])[CH2:5][N:6]([CH2:13][CH2:14][OH:15])[CH2:7]1)(=[O:36])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]/[CH:26]=[CH:27]\[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)OC
Reactant: OCCN1CN(CCO)CN(CCO)C1
Agent: CCCCCCCC/C=C\CCCCCCCC(=O)O
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: ClCCl
Product: CCCCCCCC/C=C\CCCCCCCC(=O)OCCN1CN(CCO)CN(CCO)C1
Temperature: 80 °C
Reaction time: 8 h

Procedure:
A mixture of 20 g of 1,3,5-tris-hydroxyethyl perhydro-s-triazine from the method of Paquin, Ber., 82, 316 (1949) and 0.30 g (5.8 mole percent) of powdered KOH is heated at 80° C. under reduced pressure (less than 0.1 mm) for 6 hours. Methyl oleate (30g ) from acid-catalyzed esterification of oleic acid in methanol is then added and the resulting mixture (in two phases) is stirred at 80° C. under the reduced pressure overnight. The homogeneous material which is obtained is dissolved in CH2Cl2, washed with water, dried over potassium carbonate, then is concentrated into a light yellow oil of 41 g (84.9 percent of theory). Both the infrared (1745 cm-1) and nuclear magnetic resonance spectra are consistent with the desired 1,3,5-triazine-1,3,5-(2H,4H,6H)triethanol monooleate.
Reaction SMILES: C(OC[O:5][CH:6]1[CH2:24][CH:23]2[N:8]([C:9](=[O:44])[N:10](CC3C=CC(OC)=CC=3)[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH:16]=[CH:17][CH:18]3[C:20]([C:26]([NH:28][S:29]([CH:32]4[CH2:34][CH2:33]4)(=[O:31])=[O:30])=[O:27])([NH:21][C:22]2=[O:25])[CH2:19]3)[CH2:7]1)C.Cl.C(=O)([O-])O.[Na+]>C1COCC1.CO>[OH:5][CH:6]1[CH2:24][CH:23]2[N:8]([C:9](=[O:44])[NH:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH:16]=[CH:17][CH:18]3[C:20]([C:26]([NH:28][S:29]([CH:32]4[CH2:33][CH2:34]4)(=[O:31])=[O:30])=[O:27])([NH:21][C:22]2=[O:25])[CH2:19]3)[CH2:7]1
Reactant: CCOCOC1CC2C(=O)NC3(C(=O)NS(=O)(=O)C4CC4)CC3C=CCCCCCN(Cc3ccc(OC)cc3)C(=O)N2C1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: O=C1NC2(C(=O)NS(=O)(=O)C3CC3)CC2C=CCCCCCNC(=O)N2CC(O)CC12
Temperature: 25 °C
Reaction time: 8 h
Yield: 73.3 %

Procedure:
A solution of the acetal 21j (0.038 g, 0.06 mmol) in 1:1:1 THF-methanol-2 M aq. hydrochloric acid (1.5 ml) was stirred at rt for 30 min, then additional conc. hydrochloric acid (0.1 ml) was added and then stirred at rt overnight. The reaction mixture was then neutralized using aq. saturated sodium hydrogen carbonate, then concentrated onto silica. Flash chromatography of the residue using 9:1 ethyl acetate methanol gave a colorless foam (0.020 g, 73%). LR-MS: Calcd for C20H29N4O6S: 453. Found: 453 [M−H].
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][N:3]=1.[CH3:14][N:15]1[CH:19]=[C:18]([CH2:20][NH2:21])[CH:17]=[N:16]1.CCN(C(C)C)C(C)C>CC#N>[Cl:1][C:2]1[N:7]=[C:6]([NH:21][CH2:20][C:18]2[CH:17]=[N:16][N:15]([CH3:14])[CH:19]=2)[C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][N:3]=1
Reactant: Cn1cc(CN)cn1
Reactant: CCOC(=O)c1cnc(Cl)nc1Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: CCOC(=O)c1cnc(Cl)nc1NCc1cnn(C)c1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a solution of ethyl 2,4-dichloropyrimidine-5-carboxylate (896 mg, 4 mmol) and (1-methyl-1H-pyrazol-4-yl)methanamine (445 mg, 4 mmol) in CH3CN (6 mL) at room temperature, DIEA (0.783 mL, 4.4 mmol) was added. The mixture was stirred at room temperature for 24 h, and was concentrated to give ethyl 2-chloro-4-((1-methyl-1H-pyrazol-4-yl)methylamino)pyrimidine-5-carboxylate as crude oil.
Reaction SMILES: [Br:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:6][CH:5]=1.Cl.[I:18]N1C(=O)CCC1=O.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(#N)C.O.C(O)C>[Br:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[C:6]([I:18])[CH:5]=1
Reactant: O=C1CCC(=O)N1I
Reactant: CCOC(=O)CNc1ccc(CCBr)cc1
Agent: Cl
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: O
Solvent: CCO
Solvent: CC#N
Product: CCOC(=O)CNc1ccc(CCBr)cc1I
Reaction time: 1 h
Yield: 53.8 %

Procedure:
To a stirred solution of ethyl N-[4-(2-bromoethyl)-phenyl]aminoacetate (580 mg) in acetonitrile (4.05 ml) were added concentrated hydrochloric acid (169 μl) and N-iodosuccinimide (912 mg) under ice-cooling, and the mixture was stirred for 1 hour. Ethanol (4.0 ml) was added to the reaction mixture, and the mixture was stirred for 45 minutes under ice-cooling. A solution of sodium thiosulfate (640 mg) in water (20 ml) was added to the reaction mixture, and the mixture was stirred for 1 hour under ice-cooling. The reaction mixture was diluted with water and extracted with ethyl acetate. The extract was washed with brine and dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. Purification of the residue by medium pressure liquid column chromatography on silica gel (eluent: hexane/ethyl acetate=9/1) gave ethyl N-[4-(2-bromoethyl) -2-iodophenyl]aminoacetate (449 mg).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][OH:5].[CH:6]([S:8]([CH:11]=[CH2:12])(=[O:10])=[O:9])=[CH2:7]>>[O:9]=[S:8]1(=[O:10])[CH2:11][CH2:12][N:1]([CH2:2][CH2:3][CH2:4][OH:5])[CH2:7][CH2:6]1
Reactant: NCCCO
Reactant: C=CS(=O)(=O)C=C
Product: O=S1(=O)CCN(CCCO)CC1
Temperature: 110 °C
Yield: 49.3 %

Procedure:
A mixture of 3-amino-1-propanol (650 μl, 8.4 mmol) and vinyl sulphone (1 g, 8.4 mmol) was heated at 110° C. for 45 minutes. The mixture was allowed to cool and was purified by column chromatography eluting with methylene chloride/methanol (95/5) to give 3-(1,1-dioxothiomorpholino)-1-propanol (800 mg, 90%).
Reaction SMILES: [NH2:1][CH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3]1.[C:11](Cl)(=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=1>CCCCCC>[C:11]([NH:1][CH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3]1)(=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=1
Reactant: COc1cccc(C(=O)Cl)c1
Reactant: NC1CCc2ccccc21
Solvent: CCCCCC
Product: COc1cccc(C(=O)NC2CCc3ccccc32)c1

Procedure:
The title compound was prepared from (rac)-1-aminoindan (1.6 g, 12.3 mmole) and m-anisoyl chloride (1.9 g, 13.54 mmole) as in Ex. 46; crystallization from EtOAc:hexane gave 2.0 g (7.2 mmole, 59%) white solid, mp: 140° C.
Reaction SMILES: [OH:1][C@@H:2]1[C@H:6]([CH2:7][NH:8][C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:5][N:4](C(OC(C)(C)C)=O)[CH2:3]1.O[C@H]1[C@@H](CNC(OCC2C=CC=CC=2)=O)CN(C(OC(C)(C)C)=O)C1.FC(F)(F)C(O)=O.CC[NH+](CC)CC.CC[NH+](CC)CC.C([O-])([O-])=O>C(Cl)Cl.CO>[OH:1][C@H:2]1[CH2:3][NH:4][CH2:5][C@H:6]1[CH2:7][NH:8][C:9](=[O:10])[O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CC(C)(C)OC(=O)N1C[C@@H](CNC(=O)OCc2ccccc2)[C@@H](O)C1
Agent: CC(C)(C)OC(=O)N1C[C@H](CNC(=O)OCc2ccccc2)[C@H](O)C1
Agent: CC[NH+](CC)CC
Agent: O=C([O-])[O-]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: CO
Product: O=C(NC[C@@H]1CNC[C@@H]1O)OCc1ccccc1
Reaction time: 2 h
Yield: 100 %

Procedure:
To a stirred solution of 1,1-dimethylethyl (3R,4R)-3-hydroxy-4-[({[(phenylmethyl)oxy]carbonyl}amino)methyl]-1-pyrrolidinecarboxylate (for a synthesis see WO2006002047, Preparation 24(c) (±)-1,1-dimethylethyl cis-3-hydroxy-4-[({[(phenylmethyl)oxy]carbonyl}amino)methyl]-1-pyrrolidinecarboxylate E2 isomer) (2 g, 5.7 mmol) in DCM (50 ml) was added trifluoracetic acid (50 mL) and stirred for 2 h. The reaction mixture was concentrated and placed under high-vac for 3 h. To the TFA salt dissolved in 100 ml of 10:1 CHCl3:MeOH was added MP-carbonate resin (8 g; 22.8 mmol) and stirred overnight. The reaction mixture was filtered and concentrated to provide the title compound as a pale yellow oil (1.4 g; 100%).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:8][C:9]=1[NH2:10])=[O:4].[CH:17]([CH:19]1[CH2:24][CH2:23][CH2:22][N:21]([C:25](OCC2C=CC=CC=2)=O)[CH2:20]1)=O.C1([SiH3])C=CC=CC=1>C1COCC1.CCOC(C)=O.C([Sn](Cl)(Cl)CCCC)CCC>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:8][C:9]=1[NH:10][CH2:17][CH:19]1[CH2:24][CH2:23][CH2:22][N:21]([CH3:25])[CH2:20]1)=[O:4]
Reactant: COC(=O)c1sc(-c2ccccc2)cc1N
Reactant: O=CC1CCCN(C(=O)OCc2ccccc2)C1
Agent: CCCC[Sn](Cl)(Cl)CCCC
Agent: [SiH3]c1ccccc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COC(=O)c1sc(-c2ccccc2)cc1NCC1CCCN(C)C1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 68.7 %

Procedure:
A suspension of 3-amino-5-phenyl-thiophene-2-carboxylic acid methyl ester (0.268 g, 1.15 mmol) and 3-formyl N-Cbz-piperidine (0.284 g, 1.15 mmol) in THF (0.5 mL) was treated with dibutyltin dichloride (17 mg, 0.057 mmol). After 5 min, phenylsilane (156 □L, 1.26 mmol) was added and the mixture was stirred for 6 days at room temperature. The solvent was then evaporated and the residue was purified by silica gel column chromatography using CH2Cl2:hexanes:EtOAc as eluent to provide 3-[(1-Methyl-piperidin-3-ylmethyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester as an oil (0.2723 g, 51% yield). 1H NMR (CDCl3, 400 MHz): 7.63-7.59 (m, 2H), 7.40-7.28 (m, 9H), 7.18-6.84 (br s, 1H), 5.20 (d, 1H), 5.10 (d, 1H), 4.55 (m, 1H), 4.15 (m, 1H), 3.82 (s, 3H), 3.58-3.40 (m, 2H), 2.90 (t, 1H), 1.88-1.40 (m, 6H).
Reaction SMILES: O=[C:2]([CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[CH3:17]OC(OC)N(C)C.[C:25]1([NH:31][NH2:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>C(O)C>[C:25]1([N:31]2[CH:17]=[C:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])[C:2]([CH2:9][CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[N:32]2)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: CCOC(=O)CC(=O)CCc1ccccc1
Reactant: COC(OC)N(C)C
Reactant: NNc1ccccc1
Solvent: CCO
Product: CCOC(=O)c1cn(-c2ccccc2)nc1CCc1ccccc1
Temperature: 100 °C
Reaction time: 8 h
Yield: 84 %

Procedure:
A mixture of ethyl 3-oxo-5-phenylpentanoate (5.8 g) and dimethylformamide dimethylacetal (3.6 mL) was stirred at 100° C. overnight, and the mixture was allowed to cool to room temperature. To the reaction mixture were added ethanol (30 mL) and phenylhydrazine (2.9 g), and the mixture was further stirred at 100° C. for 8 hr. After allowing to cool, ethanol was evaporated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:10, volume ratio) to give the title object compound (7.1 g, 84%) as a yellow oil.
Reaction SMILES: [CH3:1][C:2]1[NH:6][C:5]2[C:7](=[O:10])[CH2:8][CH2:9][C:4]=2[C:3]=1[C:11]([OH:13])=O.[CH:14]1[CH:15]=[CH:16][C:17]2N(O)N=N[C:18]=2[CH:19]=1.C(Cl)CCl.[NH2:28][C:29]1C=CC=CC=1>CN(C=O)C.C([O-])([O-])=O.[Na+].[Na+].O>[CH2:29]([NH:28][C:11]([C:3]1[C:4]2[CH2:9][CH2:8][C:7](=[O:10])[C:5]=2[NH:6][C:2]=1[CH3:1])=[O:13])[C:18]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:19]=1
Reactant: Nc1ccccc1
Reactant: On1nnc2ccccc21
Reactant: Cc1[nH]c2c(c1C(=O)O)CCC2=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Solvent: ClCCCl
Product: Cc1[nH]c2c(c1C(=O)NCc1ccccc1)CCC2=O
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 78.3 %

Procedure:
A mixture of 2-methyl-6-oxo-1,4,5,6-tetrahydro-cyclopenta[b]pyrrole-3-carboxylic acid (Example B, 268.5 mg, 1.5 mmol), HOBt (202.5 mg, 1.5 mmol) and EDC (573.5 mg, 3 mmol) in dry DMF (5 mL) was stirred at room temperature for 20 min. Then aniline (3.0 mmol) was added to the mixture and stirring was continued for 24 hours. The reaction was diluted with sat. Na2CO3 and water, the solid was collected by vacuum filtration, washed with sat. Na2CO3 and water in turn, dried to give 315 mg of the titled compound as a white solid.
Reaction SMILES: [CH:1](=O)[CH:2]([CH3:4])[CH3:3].[CH2:6]([SH:10])[CH2:7][CH2:8][SH:9].B(F)(F)F.CCOCC>ClCCl>[CH:2]([CH:1]1[S:10][CH2:6][CH2:7][CH2:8][S:9]1)([CH3:4])[CH3:3]
Reactant: CC(C)C=O
Reactant: SCCCS
Agent: FB(F)F
Solvent: ClCCl
Solvent: CCOCC
Product: CC(C)C1SCCCS1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 98.6 %

Procedure:
To a mixture of isobutyraldehyde (9.1 mL, 100 mmol) and 1,3-propanedithiol (10 mL, 100 mmol) in dichloromethane at 0° C. was added boron trifluoride diethyl etherate (6.4 mL, 50 mmol). The resulting mixture was stirred at 0° C. for 30 min and at room temperature for 30 min. The reaction mixture was washed with brine, 5% NaHCO3, and brine again. The organic phase was separated and dried over Na2SO4, then concentrated to give 16 g (100%) of the title compound as a yellow liquid. This was carried to the next step without further purification. 1H NMR (CDCl3, 400 MHz): δ 1.057 (d, J=7.2 Hz, 3H), 1.059 (d, J=7.2 Hz, 3H), 1.80 (m, 1H), 1.97-2.08 (m, 2H), 2.82 (m, 4H), 4.00 (d, J=5.2 Hz, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:32]=[CH:31][C:5]2[O:6][C:7]3[CH:30]=[CH:29][CH:28]=[CH:27][C:8]=3[CH2:9][N:10]([C:11](=[O:26])[CH2:12][NH:13][C:14](=[O:25])[CH2:15][CH2:16][NH:17]C(=O)OC(C)(C)C)[C:4]=2[CH:3]=1.C(O)(=O)C.Cl>O1CCOCC1>[ClH:1].[NH2:17][CH2:16][CH2:15][C:14]([NH:13][CH2:12][C:11]([N:10]1[CH2:9][C:8]2[CH:27]=[CH:28][CH:29]=[CH:30][C:7]=2[O:6][C:5]2[CH:31]=[CH:32][C:2]([Cl:1])=[CH:3][C:4]1=2)=[O:26])=[O:25]
Reactant: CC(C)(C)OC(=O)NCCC(=O)NCC(=O)N1Cc2ccccc2Oc2ccc(Cl)cc21
Agent: Cl
Solvent: C1COCCO1
Solvent: CC(=O)O
Product: NCCC(=O)NCC(=O)N1Cc2ccccc2Oc2ccc(Cl)cc21

Procedure:
A solution of 1,1-dimethylethyl [3-[[2-(8-chloro-10,11-dihydrodibenz[b,f][1,4]-oxazepin-10-yl)-2oxoethyl]amino]-3-oxopropyl]carbamate (8.1 grams), glacial acetic acid (50 mL), and 6.95M HCl in dioxane (27 mL) was stirred at room temperature for 20 minutes. The reaction was evaporated in vacuo, and the residue was co-evaporated in vacuo twice with ethanol (3A; 170 mL each time). The resulting foam was crystallized from ethyl acetate/ethanol and dried in vacuo at 56° C. The yield of the title compound was 5.79 grams (85%). Analysis calculated for C18H26ClN3O3S×HCl: C, 54.56; H, 4.83;N, 10.60; Cl, 17.89. Found: C, 54.30; H, 4.79; N, 10.49; Cl, 16.77. DSC: 216°-217° C.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([CH:20]=O)=[CH:15][CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:29].[CH3:30][N:31]([CH3:35])[CH2:32][CH2:33][NH2:34].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.O>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([CH2:20][NH:34][CH2:33][CH2:32][N:31]([CH3:35])[CH3:30])=[CH:15][CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:29]
Reactant: CC(C)(C)OC(=O)n1c(-c2ccc(Cl)c3c2C(=O)NC3)cc2cc(C=O)ccc21
Reactant: CN(C)CCN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Solvent: CC#N
Product: CN(C)CCNCc1ccc2c(c1)cc(-c1ccc(Cl)c3c1C(=O)NC3)n2C(=O)OC(C)(C)C
Yield: 109.5 %

Procedure:
In a similar manner to Step 2 of Example 6, 4-chloro-7-[1-(tert-butoxycarbonyl)-5-formylindol-2-yl]isoindolinone (40.0 mg, 0.0974 mmol) was dissolved in acetonitrile (2 mL), and the solution was treated with N,N-dimethylethylenediamine (0.043 mL, 0.39 mmol), acetic acid (0.112 mL, 1.96 mmol) and sodium triacetoxyborohydride (103 mg, 0.486 mmol). The reaction mixture was added with water and sodium carbonate to adjust the pH to 9, followed by extracting with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to obtain 4-chloro-7-(1-(tert-butoxycarbonyl)-5-[(2-dimethylaminoethyl)aminomethyl]indol-2-yl)isoindolinone (51.5 mg).
Reaction SMILES: [C:1]1(=O)[O:6][C:4](=[O:5])[CH:3]=[CH:2]1.[H][H]>O1CCCC1>[C:4]1(=[O:5])[O:6][CH2:1][CH2:2][CH2:3]1.[CH2:1]([OH:6])[CH2:2][CH2:3][CH2:4][OH:5]
Reactant: O=C1C=CC(=O)O1
Reactant: [H][H]
Solvent: C1CCOC1
Product: O=C1CCCO1
Product: OCCCCO

Procedure:
Continuous production can be carried out by either the flooded-bed or the trickle-bed method. In batchwise hydrogenation a typical procedure is to charge a high-pressure autoclave with maleic anhydride dissolved in tetrahydrofuran and the catalyst, introduce hydrogen under pressure, and heat the mixture. When the reaction is completed the mixture is cooled, the catalyst is separated off, and the tetrahydrofuran, gamma-butyrolactone, and 1,4-butanediol are isolated by fractional distillation. If required it is also possible to post-hydrogenate the gamma-butyrolactone to 1,4-butanediol and tetrahydrofuran, then to cyclize the 1,4-butanediol in the usual way.
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH2:8][OH:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].CN(C)C1C=CC=CC=1.[Br:21][CH2:22][C:23](Br)=[O:24]>C(OC(C)C)(C)C.C(OCC)C>[Br:21][CH2:22][C:23]([O:9][CH2:8][C:7]1[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:11][CH:10]=1)=[O:24]
Reactant: O=C(Br)CBr
Reactant: O=[N+]([O-])c1ccc(CO)cc1
Solvent: CCOCC
Solvent: CN(C)c1ccccc1
Solvent: CC(C)OC(C)C
Product: O=C(CBr)OCc1ccc([N+](=O)[O-])cc1
Temperature: 0 °C

Procedure:
To a mixture of p-nitrobenzyl alcohol (45 g) and N,N-dimethylaniline (37.2 ml) in a mixture of diisopropyl ether and diethyl ether (300 ml) was added dropwise bromoacetyl bromide (25 ml) at 30° to 35° C., and the reaction mixture was stirred at the same temperature for an hour. After the reaction mixture was poured into ice-water, the separated organic layer was washed with 5% aqueous sodium bicarbonate. The solution was evaporated under reduced pressure to give p-nitrobenzyl bromoacetate. To a solution of this residue in N,N-dimethylformamide (150 ml) was added N-hydroxyphthalimide (39.3 g) and triethylamine (50 ml), and the reaction mixture was stirred for an hour at room temperature. The resultant mixture was poured into ice-water, and the precipitates were collected by filtration and washed with water to give p-nitrobenzyl 2-phthalimidooxyacetate (69.29 g).
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[C:7]2[NH:15][N:14]=[N:13][C:8]=2[N:9]=[C:10]([NH2:12])[N:11]=1.Br[CH2:17][C:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:19].C(N(CC)CC)C>CN(C=O)C.O>[NH2:12][C:10]1[N:11]=[C:6]([C:2]2[O:1][CH:5]=[CH:4][CH:3]=2)[C:7]2[N:15]=[N:14][N:13]([CH2:17][C:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[O:19])[C:8]=2[N:9]=1
Reactant: O=C(CBr)c1ccccc1
Reactant: Nc1nc(-c2ccco2)c2[nH]nnc2n1
Solvent: CCN(CC)CC
Solvent: O
Solvent: CN(C)C=O
Product: Nc1nc(-c2ccco2)c2nnn(CC(=O)c3ccccc3)c2n1
Temperature: 25 °C
Reaction time: 72 h
Yield: 12.5 %

Procedure:
A solution of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (101 mg, 0.5 mmol) in DMF (2 mL) was treated with 2-bromoacetophenone (100 mg, 0.5 mmol) and triethylamine (105 μL, 0.75 mmol), stirred at room temperature for 3 days, diluted with water (100 mL) and filtered. The resulting solid was purified by chromatography [SiO2; Hexane:EtOAc, (3:1 to 1:1)] to give the title compound (20 mg, 13%) as a yellow solid.