Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([Mg]Cl)(C)C.[Si:6]([O:13][CH2:14][C@@H:15]([N:17]1[C:21]2[N:22]=[CH:23][N:24]=[CH:25][C:20]=2[C:19](I)=[CH:18]1)[CH3:16])([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].[C:27]1([C:33](=[N:40][C:41]2[CH:42]=[N:43][CH:44]=[C:45]([CH:52]=2)[C:46](N(OC)C)=[O:47])[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C1COCC1>[Si:6]([O:13][CH2:14][C@@H:15]([N:17]1[C:21]2[N:22]=[CH:23][N:24]=[CH:25][C:20]=2[C:19]([C:46]([C:45]2[CH:44]=[N:43][CH:42]=[C:41]([N:40]=[C:33]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:52]=2)=[O:47])=[CH:18]1)[CH3:16])([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7]
Reactant: C[C@@H](CO[Si](C)(C)C(C)(C)C)n1cc(I)c2cncnc21
Reactant: CON(C)C(=O)c1cncc(N=C(c2ccccc2)c2ccccc2)c1
Agent: CC(C)[Mg]Cl
Solvent: C1CCOC1
Product: C[C@@H](CO[Si](C)(C)C(C)(C)C)n1cc(C(=O)c2cncc(N=C(c3ccccc3)c3ccccc3)c2)c2cncnc21
Temperature: 0 °C
Reaction time: 1 h

Procedure:
Isopropyl magnesium chloride (68.8 mL, 138 mmol, 2.0 M in THF) was added to 7-[(1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyl]-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (52.2 g, 125 mmol) (see Preparation 14) in THF (400 mL) at 0° C., under nitrogen. The mixture was stirred at 0° C. for 1 hour then a solution of 5-[(diphenylmethylene)amino]-N-methoxy-N-methylnicotinamide (47.5 g, 138 mmol) (see Preparation 23) in THF (100 mL) was added dropwise at 0° C. The mixture was warmed to room temperature and stirred at this temperature for 16 hours. The reaction mixture was quenched with 10% aqueous ammonium chloride (250 mL) and extracted with ethyl acetate (2×250 mL).
Reaction SMILES: [CH2:1]([CH2:3][NH2:4])[OH:2].F[C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-])=O)=[CH:8][CH:7]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[OH:2][CH2:1][CH2:3][NH:4][C:6]1[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][CH:7]=1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: NCCO
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: Nc1ccc(NCCO)cc1
Temperature: 90 °C
Yield: 20 %

Procedure:
A mixture of ethanolamine (2.29 g, 37.5 mmol) and 1-fluoro-4-nitrobenzene (3.53 g, 25.0 mmol) in dimethylsulphoxide (25 ml) was treated with potassium carbonate (6.9 g, 50 mmol) and heated at 90° C. overnight. The mixture was cooled and poured onto water (250 ml), the precipitated solid filtered off, dried, dissolved in ethanol (50 ml) and hydrogenated over 10% Pd/C for 4 h at ambient temperature . The catalyst was removed by filtration, the ethanol evaporated and the residue purified by column chromatography using EtOAc to yield the title compound (740 mg, 5.0 mmol). NMR: 2.95 (t, 2H), 3.5 (t, 2H), 4.1 (s, 2H), 4.4 (s, 1H), 4.55 (t, 1H), 6.4 (m, 4H); MS: 153 (M+H)+.
Reaction SMILES: N[CH:2]1[C:25](=[O:26])[N:4]2[C:5]([C:22]([OH:24])=[O:23])=[C:6](CSC3N(CCCCCC)N=NN=3)[CH2:7][S:8][C@H:3]12.C[Si](CC(N)=O)(C)C.C(Cl)Cl.C(=O)(O)[O-].[Na+]>O.C(OCC)(=O)C>[S:8]1[C@@H:3]2[CH2:2][C:25](=[O:26])[N:4]2[C:5]([C:22]([OH:24])=[O:23])=[CH:6][CH2:7]1
Reactant: CCCCCCn1nnnc1SCC1=C(C(=O)O)N2C(=O)C(N)[C@H]2SC1
Agent: C[Si](C)(C)CC(N)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Solvent: CCOC(C)=O
Product: O=C(O)C1=CCS[C@@H]2CC(=O)N12
Temperature: -15 °C
Reaction time: 0.5 h

Procedure:
On the other hand, a mixture of 7-amino-3-[(1-hexyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylic acid (5.89 g) and trimethylsilyl acetamide (16 g) is methylene chloride (150 ml) was warmed to make a clear solution. The solution was cooled to -15° C. and added all at once to the activated acid solution prepared above. The reaction mixture was stirred for 30 minutes at -15° to 0° C. and for additional 30 minutes at ambient temperature. The solvent was removed by distillation from the reaction mixture under reduced pressure to give a residue, to which ethyl acetate (150 ml) and water (100 ml) were added, and then the mixed solution was adjusted to pH 3 with an aqueous solution of sodium bicarbonate. The organic layer was separated out, washed two times with an aqueous solution of sodium chloride and dried over magnesium sulfate, and then evaporated to dryness to give a brownish oil. This oil was washed three times with diethyl ether (70 ml) and triturated with diisopropyl ether to give a powder of 7-[2-(6-formamidopyridin-2-yl)-2-hydroxyiminoacetamido]-3-(1-hexyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylic acid (syn isomer), mp 74°-84° C. (dec.).
Reaction SMILES: C(OC(=O)[NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17](=[O:48])[CH2:18][N:19]2[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[N:21]=[C:20]2[C:28]2[C:32]([NH:33][C:34](=[O:47])[CH2:35][NH:36]C(OCC3C=CC=CC=3)=O)=[N:31][O:30][N:29]=2)=[CH:13][CH:12]=1)C1C=CC=CC=1.[ClH:50].O1CCOCC1>O1CCCC1.CO.[Pd]>[ClH:50].[NH2:36][CH2:35][C:34]([NH:33][C:32]1[C:28]([C:20]2[N:19]([CH2:18][C:17]([C:14]3[CH:15]=[CH:16][C:11]([NH2:10])=[CH:12][CH:13]=3)=[O:48])[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[N:21]=2)=[N:29][O:30][N:31]=1)=[O:47]
Reactant: O=C(CNC(=O)OCc1ccccc1)Nc1nonc1-c1nc2ccccc2n1CC(=O)c1ccc(NC(=O)OCc2ccccc2)cc1
Agent: [Pd]
Agent: Cl
Solvent: C1COCCO1
Solvent: CO
Solvent: C1CCOC1
Product: NCC(=O)Nc1nonc1-c1nc2ccccc2n1CC(=O)c1ccc(N)cc1
Temperature: 25 °C
Reaction time: 7 h

Procedure:
A mixture of 0.2 g of [4-(2-{2-[4-(2-benzyloxycarbonylamino-acetylamino)-furazan-3-yl]-benzoimidazol-1-yl}-acetyl)-phenyl]-carbamic acid benzyl ester (0.29 mmol; 1 eq.) in 2 mL of tetrahydrofuran and 2 mL of methanol containing 0.19 mL of a solution of 4M HCl in 1,4-dioxane (0.86 mmol; 3 eq.) and 0.046 g of 10% Pd/C (0.04 mmol; 0.14 eq.) is stirred for 7 hours under hydrogen atmosphere at room temperature. Then the mixture is filtered and the filtrate is concentrated under reduced pressure. The residue is suspended in 2 mL of a mixture of dichloromethane/diisopropylether (1/1, v/v) and the suspension is filtered. The solid is washed with 2 mL of diisopropylether and dried under reduced pressure to give the crude product. The solid is purified by MCI gel column chromatography (eluent water/acetonitrile=75/25 to 65/35, containing 0.1% of HCl) to afford 0.02 g of the desired product as a light brown powder.
Reaction SMILES: [F:1][C:2]1[C:15]([F:16])=[C:14]([F:17])[C:13]([F:18])=[CH:12][C:3]=1[C:4]([CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])=[O:5].[CH3:19]C(OC(C)=O)=O.C(OCC)(OCC)OCC.[NH2:36][CH2:37][CH2:38][CH2:39][CH2:40][OH:41]>>[OH:41][CH2:40][CH2:39][CH2:38][CH2:37][NH:36][CH:19]=[C:6]([C:4](=[O:5])[C:3]1[CH:12]=[C:13]([F:18])[C:14]([F:17])=[C:15]([F:16])[C:2]=1[F:1])[C:7]([O:9][CH2:10][CH3:11])=[O:8]
Reactant: CC(=O)OC(C)=O
Reactant: NCCCCO
Reactant: CCOC(=O)CC(=O)c1cc(F)c(F)c(F)c1F
Solvent: CCOC(OCC)OCC
Product: CCOC(=O)C(=CNCCCCO)C(=O)c1cc(F)c(F)c(F)c1F
Temperature: 130 °C
Reaction time: 3 h
Yield: 97.2 %

Procedure:
A mixture of ethyl 2,3,4,5-tetrafluorobenzoylacetate (2.64 g, 10.0 mmol), Ac2O (2.36 mL, 25.0 mmol) and triethyl orthoformate (2.49 mL, 15.0 mmol) was stirred at 130° C. for 3 h. The mixture was concentrated in vacuo and dried under high vacuum. The crude product was dissolved in EtOH (50 mL) and 4-amino-1-butanol (0.972 mL, 10.5 mmol) was added. After stirred at room temperature for 17 h, the mixture was concentrated in vacuo and the crude product was purified by column chromatography (Hexane:EtOAc 2:1→1:2) to yield ethyl 3-(4-hydroxybutylamino)-2-(2,3,4,5-tetrafluorobenzoyl)acrylate (3.53 g, 97%) as a pale yellow solid.
Reaction SMILES: [CH3:1][N:2]1[C:9](=[O:10])[CH2:8][C:6](=[O:7])[N:5]([CH3:11])[C:3]1=[O:4].C(N(CC)CC)C.[Cl:19][C:20]1[CH:21]=[C:22]([N:31]=[C:32]=[O:33])[CH:23]=[CH:24][C:25]=1[O:26][C:27]([F:30])([F:29])[F:28].Cl>O1CCOCC1>[Cl:19][C:20]1[CH:21]=[C:22]([NH:31][C:32]([CH:8]2[C:9](=[O:10])[N:2]([CH3:1])[C:3](=[O:4])[N:5]([CH3:11])[C:6]2=[O:7])=[O:33])[CH:23]=[CH:24][C:25]=1[O:26][C:27]([F:30])([F:29])[F:28]
Reactant: O=C=Nc1ccc(OC(F)(F)F)c(Cl)c1
Reactant: CN1C(=O)CC(=O)N(C)C1=O
Agent: Cl
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: CN1C(=O)C(C(=O)Nc2ccc(OC(F)(F)F)c(Cl)c2)C(=O)N(C)C1=O
Reaction time: 5 h
Yield: 83.8 %

Procedure:
7.8 g (0.05 mol) of 1,3-dimethylbarbituric acid were suspended in 150 ml of dioxane and 5 g (0.05 mol) of triethylamine, and 11.85 g (0.05 mol) of 3-chloro-4-trifluoromethoxy-phenyl isocyanate were added. The mixture was stirred for 5 hours under reflux. When it had cooled, the reaction mixture was brought to a pH value of 3 with 2 N hydrochloric acid and was concentrated in vacuo by distilling off the solvent. The residue was mixed with 200 ml of water, filtered off, mixed with 100 ml of isopropanol, again filtered off and dried. 16.5 g (74% of theory) of 5-(3'-chloro-4'-trifluoromethoxy-phenyl-carbamoyl)-1,3-dimethyl-barbituric acid, of melting point 160° C., were obtained.