Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N[C@H](C(O)=O)C([SH:6])(C)C.C[Si](C)(C)S[Si](C)(C)C.C[O-].[Na+].[F:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:48]=[CH:47][C:32]3[N:33]=[C:34]([C:39]4[CH:40]=[C:41]([CH:44]=[CH:45][CH:46]=4)[C:42]#[N:43])[CH2:35][C:36](=[O:38])[NH:37][C:31]=3[CH:30]=2)=[CH:25][CH:24]=1>CN1CCN(C)C1=O.O>[F:22][C:23]1[CH:24]=[CH:25][C:26]([C:29]2[CH:48]=[CH:47][C:32]3[N:33]=[C:34]([C:39]4[CH:40]=[C:41]([CH:44]=[CH:45][CH:46]=4)[C:42]([NH2:43])=[S:6])[CH2:35][C:36](=[O:38])[NH:37][C:31]=3[CH:30]=2)=[CH:27][CH:28]=1
Reactant: N#Cc1cccc(C2=Nc3ccc(-c4ccc(F)cc4)cc3NC(=O)C2)c1
Reactant: CC(C)(S)[C@H](N)C(=O)O
Agent: C[O-]
Agent: C[Si](C)(C)S[Si](C)(C)C
Agent: [Na+]
Solvent: CN1CCN(C)C1=O
Solvent: O
Product: NC(=S)c1cccc(C2=Nc3ccc(-c4ccc(F)cc4)cc3NC(=O)C2)c1
Reaction time: 0.08 h

Procedure:
Preparation of 4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-thiobenzamides (according to Pen-Yuan Lin et al. Synthesis 1992, 1219]: To a solution of hexamethyldisilthiane (1.45 g, 8.0 mmol) in 1,3-dimethyl-2-imidazolidinone (8 mL) was added at 23° C. sodium methoxide (0.31 g, 6.8 mmol). The mixture was stirred for 5 min. and the blue solution formed was then added to a solution of 3-[7-(4-fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile (Example 57) (1.42 g, 4 mmol) in 1,3-dimethyl-2-imidazolidinone (12 mL). The mixture was stirred for 3 h at 23° C. and then poured into water (100 mL). Stirring was continued for 0.5 h and the precipitate was isolated by filtration and triturated with ethyl acetate (50 mL) to give the title compound as light yellow solid (1.38 g).
Reaction SMILES: [CH3:1][C:2]([O:5][C:6](=[O:34])[NH:7][C@H:8]1[C:11](=[O:12])[N:10](C2C=CC(OC)=CC=2)[C@H:9]1[CH2:21][O:22][N:23]1C(=O)C2[C:25](=CC=CC=2)[C:24]1=[O:33])([CH3:4])[CH3:3].N1C=CC=CC=1.C(Cl)(=O)C>C(Cl)Cl.CN(C=O)C>[CH3:4][C:2]([O:5][C:6](=[O:34])[NH:7][C@H:8]1[C:11](=[O:12])[NH:10][C@H:9]1[CH2:21][O:22][NH:23][C:24](=[O:33])[CH3:25])([CH3:1])[CH3:3]
Reactant: COc1ccc(N2C(=O)[C@H](NC(=O)OC(C)(C)C)[C@@H]2CON2C(=O)c3ccccc3C2=O)cc1
Solvent: CN(C)C=O
Solvent: CC(=O)Cl
Solvent: ClCCl
Product: CC(=O)NOC[C@@H]1NC(=O)[C@@H]1NC(=O)OC(C)(C)C
Reaction time: 0.25 h
Yield: 88.4 %

Procedure:
To the oxyamine produced in Example 1 (400 mg, 1.73 mmol) dissolved in a solution of CH2Cl2 -DMF (1:1) at 0° C. was added pyridine (1.1 eq.) followed by acetyl chloride (1.1 eq.). The reaction was allowed to stir for 15 minutes followed by removal of the solvents under reduced pressure. The residue obtained was purified by flash chromatography (5% CH3OH in CH2Cl2 to 10% CH3OH in CH2Cl2) to afford [cis-2-[[(acetylamino)oxy]methyl]-4-oxo-3-azetidinyl]carbamic acid 1,1-dimethylethyl ester (418 mg, 88.6%): IR (KBr) 3290, 2980, 1760, 1690, 1365, and 1160 cm-1 ; NMR (80 MHz, DMSO-d6) δ 1.40 (9H, s), 1.73 (3H, s), 3.83 (3H, m), 4.90 (1H, dd, J=9, 5 Hz), 7.60 (1H, d, J=9 Hz, exchangeable), 8.55 (1H, s, exchangeable); FAB HRMS, m/e 274.1400 (MH+ calculated for C11H20O5N3 : 274.1403).
Reaction SMILES: [N:1]1([C:7]2[N:8]=[C:9]([CH2:14][C:15]([O-:17])=O)[NH:10][C:11](=[O:13])[CH:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Na+].[I:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23]>>[I:19][C:20]1[CH:21]=[C:22]([NH:23][C:15](=[O:17])[CH2:14][C:9]2[NH:10][C:11](=[O:13])[CH:12]=[C:7]([N:1]3[CH2:2][CH2:3][O:4][CH2:5][CH2:6]3)[N:8]=2)[CH:24]=[CH:25][CH:26]=1
Reactant: Nc1cccc(I)c1
Reactant: O=C([O-])Cc1nc(N2CCOCC2)cc(=O)[nH]1
Agent: [Na+]
Product: O=C(Cc1nc(N2CCOCC2)cc(=O)[nH]1)Nc1cccc(I)c1
Yield: 76.4 %

Procedure:
The product is prepared according to the procedure described in Example 5, using 268 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate and 324 mg of 3-iodoaniline in place of the 2,4-difluoroaniline. 345 mg of N-(3-iodophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide are obtained in the form of a white solid, the characteristics of which are the following:
Reaction SMILES: [CH3:1][C:2]1([CH3:27])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[C:11]([CH:24]=[CH:25][CH:26]=2)/[CH:12]=[CH:13]/[C:14]2[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=2)[O:3]1>CO.O=[Pt]=O>[CH3:7][C:6]1([CH3:8])[C:2]([CH3:1])([CH3:27])[O:3][B:4]([C:9]2[CH:10]=[C:11]([CH:24]=[CH:25][CH:26]=2)[CH2:12][CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:22][CH:23]=2)[O:5]1
Reactant: COC(=O)c1ccc(/C=C/c2cccc(B3OC(C)(C)C(C)(C)O3)c2)cc1
Agent: O=[Pt]=O
Solvent: CO
Product: COC(=O)c1ccc(CCc2cccc(B3OC(C)(C)C(C)(C)O3)c2)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 44.7 %

Procedure:
A mixture of (E)-methyl 4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)styryl)benzoate (200 mg, 0.55 mmol) and PtO2 (50 mg, 0.22 mmol) in 30 mL of MeOH was stirred at room temperature for 18 hours under H2 atmosphere. The solvent was evaporated and the residue was purified by silica gel chromatography (200-300 mesh, eluting with a mixture of petroleum ether and ethyl acetate=50:1) to give methyl 4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenethyl)benzoate (90 mg, 50%) as a colorless oil
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH2:13]([CH:15]([CH2:18][CH3:19])[CH2:16]O)[CH3:14]>C1(C)C=CC(S(O)(=O)=O)=CC=1>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:8]([O:10][CH2:16][CH:15]([CH2:18][CH3:19])[CH2:13][CH3:14])=[O:9])=[CH:11][CH:12]=1)([O-:3])=[O:2]
Reactant: CCC(CC)CO
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Product: CCC(CC)COC(=O)c1ccc([N+](=O)[O-])cc1
Reaction time: 2 h
Yield: 83.2 %

Procedure:
A mixture of 167 g of p-nitrobenzoic acid, 204 g of 2-ethyl-1-butanol and 3.5 g of p-toluenesulfonic acid is refluxed and stirred for 2 hours, separating the formed water. After that, the alcohol excess is distilled off, then the formed product is distilled at 150° C. and 0.04 mmHg, to obtain 209 g of 2-ethylbutyl p-nitrobenzoate in form of a light yellow viscous liquid.
Reaction SMILES: N([O-])=O.[Na+].[CH3:5][S:6][C:7]1[S:8][C:9]([C:13]#[N:14])=[C:10](N)[N:11]=1.Cl.C(Cl)[Cl:17]>O>[CH3:5][S:6][C:7]1[S:8][C:9]([C:13]#[N:14])=[C:10]([Cl:17])[N:11]=1
Reactant: CSc1nc(N)c(C#N)s1
Reactant: ClCCl
Agent: Cl
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: CSc1nc(Cl)c(C#N)s1
Temperature: 0 °C

Procedure:
A concentrated solution of 42 g of sodium nitrite in water is slowly added dropwise to a mixture of 68.4 g of 2-methylthio-4-amino-5-cyanothiazole, obtained according to example III, 100 ml of water, 300 ml of concentrated hydrochloric acid, 70 g of cuprous chloride (CuCl2.2H2O) and 800 ml of methylene chloride while stirring and cooling at approximately 0° C. After stirring for another 30 minutes at 0°-5° C. the mixture is diluted with water. The reaction mixture is filtered off and the filtrate is separated; the organic layer is washed with water, dried, filtered and evaporated while adding isopropanol until crystallisation. The desired compound is obtained in a yield of 46.3 g; m.p. 83°-87° C.
Reaction SMILES: Br[CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([CH3:16])=[CH:10][C:11](=[O:15])[O:12]2)=[CH:7][CH:6]=1.[CH2:17]([O:19][P:20]([O:24]CC)[O:21][CH2:22][CH3:23])[CH3:18]>>[CH2:17]([O:19][P:20]([CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([CH3:16])=[CH:10][C:11](=[O:15])[O:12]2)=[CH:7][CH:6]=1)(=[O:24])[O:21][CH2:22][CH3:23])[CH3:18]
Reactant: CCOP(OCC)OCC
Reactant: Cc1cc(=O)oc2cc(OCCBr)ccc12
Product: CCOP(=O)(CCOc1ccc2c(C)cc(=O)oc2c1)OCC
Reaction time: 1 h

Procedure:
28.32 g. (0.1 mole) 7-(2'-bromo-ethyl-oxy)-4-methyl-coumarin and 33.23 g. (0.2 mole) triethylphosphite are heated under stirring for 1 hour. The reaction mixture is then cooled. The end-product is separated from the contaminations by removing same by vacuum distillation. The bottom product is a yellow, thick, oily substance of weight 11.9 g. (0.0035 mole), nD31 =1.5619.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:10]2[CH2:11][CH2:12][C:13]3[C:18]([C:9]=2[N:8]([CH3:20])[C:7]=1[C:21]([O:23]C(C)(C)C)=[O:22])=[N:17][C:16]([NH2:19])=[N:15][CH:14]=3)=[O:5])[CH3:2].Cl>CCO>[CH2:1]([O:3][C:4]([C:6]1[C:10]2[CH2:11][CH2:12][C:13]3[C:18]([C:9]=2[N:8]([CH3:20])[C:7]=1[C:21]([OH:23])=[O:22])=[N:17][C:16]([NH2:19])=[N:15][CH:14]=3)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1c2c(n(C)c1C(=O)OC(C)(C)C)-c1nc(N)ncc1CC2
Agent: Cl
Solvent: CCO
Product: CCOC(=O)c1c2c(n(C)c1C(=O)O)-c1nc(N)ncc1CC2

Procedure:
To a solution of 8-amino-1-methyl-4,5-dihydro-1H-1,7,9-triaza -cyclopenta[a]naphthalene-2,3-dicarboxylic acid 2-tert-butyl ester 3-ethyl ester N6 (3.76 mmol) in 20 mL of EtOH, 2N HCl (2 mL) was added. The solution was stirred at reflux for 5 h then the solvent was evaporated, affording the title compound in quantitative yield. ESI (+) MS: m/z 317 (MH+), MS (ES−) 315. 1H NMR: 1.27 (t, J=7.08, 3H), 2.79 (t, J=7.68, 2H), 2.93 (t, J=7.68, 2H), 4.15 (s, 3H), 4.23 (q, J=7.08, 2H), 7.96 (bs, 1H), 8.11 (s, 1H), 8.38 (bs, 1H).
Reaction SMILES: C(O[C:4]([N:6]1[CH2:10][C@H:9]([OH:11])[CH2:8][C@H:7]1[CH2:12][CH2:13][O:14][C:15]1[C:20]([CH3:21])=[CH:19][CH:18]=[CH:17][C:16]=1[CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[OH:11][C@H:9]1[CH2:10][N:6]([CH3:4])[C@H:7]([CH2:12][CH2:13][O:14][C:15]2[C:20]([CH3:21])=[CH:19][CH:18]=[CH:17][C:16]=2[CH2:22][CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:8]1
Reactant: CCOC(=O)N1C[C@H](O)C[C@H]1CCOc1c(C)cccc1CCc1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: Cc1cccc(CCc2ccccc2)c1OCC[C@@H]1C[C@@H](O)CN1C
Yield: 66.8 %

Procedure:
1840 mg of (2R,4R)-1-ethoxycarbonyl-4-hydroxy-2-{2-[6-methyl-2-(2-phenylethyl)phenoxy]ethyl}pyrrolidine [prepared as described in step (b) above], 20 ml of tetrahydrofuran and 530 mg of lithium aluminum hydride were allowed to react together and subsequently treated in the same manner as described in step (b) of Example 1. The concentrated substance thus obtained was purified by silica gel column chromatography, using a 5:1 by volume mixture of methylene chloride and methanol as the eluent, to give 1050 mg (yield 67%) of the title compound as a colorless solid substance.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([NH:11][C:12]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH:22]3[CH2:27][CH2:26][N:25](OCC4C=CC=CC=4)[C:24](=C=O)[CH2:23]3)[CH:16]=2)=[O:13])[N:8]([CH3:10])[N:9]=1)([CH3:4])([CH3:3])[CH3:2]>[Pd].C(O)C>[C:1]([C:5]1[CH:6]=[C:7]([NH:11][C:12]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)[CH:16]=2)=[O:13])[N:8]([CH3:10])[N:9]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: Cn1nc(C(C)(C)C)cc1NC(=O)Nc1cccc(OC2CCN(OCc3ccccc3)C(=C=O)C2)c1
Agent: [Pd]
Solvent: CCO
Product: Cn1nc(C(C)(C)C)cc1NC(=O)Nc1cccc(OC2CCNCC2)c1
Yield: 72 %

Procedure:
A mixture of 1-(5-tert-butyl-2-methyl-2H-pyrazol-3-yl)-3-{3-[1-(benzyloxy)-carbonyl-piperidin-4-yloxy]phenyl}urea. (Example 54. below, 6.62 g, 13.1 mmol) and 10% palladium on carbon (1 g) in ethanol (200 mL) is stirred at 22° C. under hydrogen gas for 2.5 hours. The catalyst is removed by filtration. The filtrate is concentrated to give brown oil, which solidifies upon standing at 22° C. over weekend. The residue is purified on a silica gel chromatography by eluting with methanol and dichloromethane. A peach color solid is obtained (3.51 g, 72% yield, ES+(m/z) 372.3 [M+H]).