Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2][CH2:3][N:4]([CH2:16][CH2:17]Cl)[C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10](=[O:15])[CH2:9][CH2:8]2.[CH3:19][O:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][NH2:26])=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Na+].[Na+]>CO>[CH3:19][O:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][N:26]2[CH2:17][CH2:16][N:4]([C:5]3[CH:6]=[C:7]4[C:12](=[CH:13][CH:14]=3)[NH:11][C:10](=[O:15])[CH2:9][CH2:8]4)[CH2:3][CH2:2]2)=[CH:23][CH:22]=1
Reactant: O=C1CCc2cc(N(CCCl)CCCl)ccc2N1
Reactant: COc1ccc(CN)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CO
Product: COc1ccc(CN2CCN(c3ccc4c(c3)CCC(=O)N4)CC2)cc1
Yield: 45.6 %

Procedure:
A mixture of 14.5 g of 6-[bis(2-chloroethyl)amino]-3,4-dihydrocarbostyril, 8.0 g of 4-methoxybenzylamine and 70 ml of methanol was stirred under reflux for 15 hours. After cooling, to the reaction mixture was added 3.06 g of sodium carbonate and the reaction mixture was stirred under reflux for 8 hours. After cooling, crystals which precipitated were collected by filtration and recrystallized from ethanol to give 8.1 g of 6-[4-(4-methoxybenzyl)-1-piperazinyl]-3,4-dihydrocarbostyril, m.p. 196°-198° C., colorless needles.
Reaction SMILES: C([O:3][C:4]([C:6]1[N:7]([CH2:15][C:16]#[N:17])[C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:5])C.O[Li].O>C1COCC1.O>[C:16]([CH2:15][N:7]1[C:8]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:14]=[C:6]1[C:4]([OH:5])=[O:3])#[N:17]
Reactant: CCOC(=O)c1cc2ccccc2n1CC#N
Agent: [Li]O
Solvent: C1CCOC1
Solvent: O
Product: N#CCn1c(C(=O)O)cc2ccccc21
Temperature: 25 °C
Reaction time: 6 h
Yield: 70 %

Procedure:
To a solution of 1.0 eq. of 1-cyanomethyl-1H-indole-2-carboxylic acid ethyl ester in a mixture of THF/H2O ((9/1) was added LiOH.H2O (1.0 eq.) and the reaction mixture stirred 6 h at RT, acidified to pH2 and then partially concentrated until precipitation of the crude product which was filtered off and washed with Et2O and then dried to give the desired product as a light yellow solid (70%).
Reaction SMILES: [CH2:1]([N:4]1[C:9](=[O:10])[C:8]([C:11]2[CH:16]=[CH:15][C:14](=[O:17])[NH:13][CH:12]=2)=[C:7]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=2)[N:6]=[C:5]1[NH2:25])[CH:2]=[CH2:3].[C:26]1(B(O)O)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.N1C=CC=CC=1>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.CN(C)C=O>[CH2:1]([N:4]1[C:9](=[O:10])[C:8]([C:11]2[CH:16]=[CH:15][C:14](=[O:17])[N:13]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:12]=2)=[C:7]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=2)[N:6]=[C:5]1[NH2:25])[CH:2]=[CH2:3]
Reactant: OB(O)c1ccccc1
Reactant: C=CCn1c(N)nc(-c2cccc(F)c2)c(-c2ccc(=O)[nH]c2)c1=O
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: c1ccncc1
Solvent: CN(C)C=O
Product: C=CCn1c(N)nc(-c2cccc(F)c2)c(-c2ccc(=O)n(-c3ccccc3)c2)c1=O
Temperature: 25 °C
Reaction time: 24 h
Yield: 32.2 %

Procedure:
In a flask were placed 3-allyl-2-amino-6-(3-fluorophenyl)-5-(6-oxo-1,6-dihydro-3-pyridinyl)-3,4-dihydro-4-pyrimidinone (20 mg, 0.06 mmol), copper acetate (3 mg, 0.01 mmol), phenylboronic acid (15 mg, 0.12 mmol), pyridine (11 μL, 0.12 mmol) and N,N-dimethylformamide (1 mL), followed by stirring at room temperature for 24 hours. After filtering off the insoluble matters by filtration, the filtrate was purified by HPLC, to give the title compound (8 mg).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:11]=[CH:12][CH:13]=1)[C:7](=[O:10])[CH2:8]Br)([O-:3])=[O:2].C([O-])(=[O:16])C.[Na+]>C(O)C>[N+:1]([C:4]1[CH:5]=[C:6]([CH:11]=[CH:12][CH:13]=1)[C:7](=[O:10])[CH2:8][OH:16])([O-:3])=[O:2]
Reactant: CC(=O)[O-]
Reactant: O=C(CBr)c1cccc([N+](=O)[O-])c1
Agent: [Na+]
Solvent: CCO
Product: O=C(CO)c1cccc([N+](=O)[O-])c1

Procedure:
Reaction of m-nitrophenacyl bromide with sodium acetate in ethanol gave m-nitrophenacyl alcohol. This was treated with dicyandiimide and HCl in aqueous methanol to give 2-guanidino4-(3-nitrophenyl)oxazole hydrochloride, m.p. 250°-251° C. The nitro residue was reduced with iron powder in acetic acid containing 10% v/v water to give 2-guanidino-4-(3-aminophenyl)oxazole.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([C:19]([F:22])([F:21])[F:20])=[CH:4][N:3]=1.[Br:23]N1C(=O)CCC1=O.O>CN(C=O)C>[Br:23][C:16]1[CH:17]=[CH:18][C:9]([NH:8][C:6]2[C:5]([C:19]([F:22])([F:20])[F:21])=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=2)=[C:10]([CH:15]=1)[C:11]([NH:13][CH3:14])=[O:12]
Reactant: O=C1CCC(=O)N1Br
Reactant: CNC(=O)c1ccccc1Nc1nc(Cl)ncc1C(F)(F)F
Solvent: CN(C)C=O
Solvent: O
Product: CNC(=O)c1cc(Br)ccc1Nc1nc(Cl)ncc1C(F)(F)F
Reaction time: 1 h
Yield: 42.2 %

Procedure:
2-{[2-chloro-5-(trifluoromethyl)pyrimidin-4-yl]amino}-N-methylbenzamide (WO 2010141406, 4.6 g, 13.9 mmol) and N-bromosuccinimide (2.46 g, 13.9 mmol) were taken up in DMF (8 mL) and stirred for 1 hr. The reaction mixture was poured into water and the resulting precipitate was collected via filtration, air dried and purified by column chromatography (SiO2, 1% methanol in dichloromethane) to give 2.4 g (42%) of the title compound. 1H NMR (600 MHz, DMSO-d6) δ: 11.88 (s, 1H), 8.93 (brs, 1H), 8.67 (s, 1H), 8.28 (d, J=9 Hz, 1H), 7.95 (s, 1H), 7.76 (d, J=9 Hz, 1H), 2.75 (d, J=4.2 Hz, 3H).
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[C:5]([O:12][CH3:13])[CH:4]=1.[P:14]([O:21]CC)([O:18][CH2:19][CH3:20])[O:15][CH2:16][CH3:17]>>[CH3:13][O:12][C:5]1[CH:4]=[C:3]([CH:8]=[CH:7][C:6]=1[N+:9]([O-:11])=[O:10])[CH2:2][P:14](=[O:21])([O:18][CH2:19][CH3:20])[O:15][CH2:16][CH3:17]
Reactant: COc1cc(CCl)ccc1[N+](=O)[O-]
Reactant: CCOP(OCC)OCC
Product: CCOP(=O)(Cc1ccc([N+](=O)[O-])c(OC)c1)OCC
Temperature: 100 °C

Procedure:
A mixture of 4-(chloromethyl)-2-methoxy-1-nitrobenzene (Compound 1H, 1.1 g, 5.46 mmol) and triethyl phosphite (1.09 g, 6.55 mmol) were heated at 100° C. for 16 h in a sealed tube. The reaction mixture was concentrated under reduced pressure to yield a black oil. The crude material was purified by silica gel chromatography on a Teledyne ISCO CombiFlash® Rf system using DCM/MeOH (100:0→95:5) as eluent to afford the title compound as 1.08 g of an orange oil (65%). MS (ESI): m/z 304.0902 [M+H]+.
Reaction SMILES: [K].[OH:2][C:3]1[C:7]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[N:6][S:5](=[O:14])[N:4]=1.CN(C=O)C.[Cl:20][C:21]1[CH:29]=[CH:28][C:24]([C:25](Cl)=[O:26])=[CH:23][CH:22]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[Cl:20][C:21]1[CH:29]=[CH:28][C:24]([C:25]([N:4]2[C:3](=[O:2])[C:7]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[N:6][S:5]2=[O:14])=[O:26])=[CH:23][CH:22]=1
Reactant: O=S1N=C(O)C(N2CCOCC2)=N1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Agent: O=C([O-])O
Agent: [K]
Agent: [Na+]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C1C(N2CCOCC2)=NS(=O)N1C(=O)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a slurry of 2.3 grams of the potassium salt (C) from Example III(a) in 10 ml methylene chloride and 5 ml DMF is added 1.5 ml p-chlorobenzoylchloride. This mixture is allowed to stir for 1 hour at room temperature. After this, saturated sodium bicarbonate solution is added and the product is extracted into methylene chloride. The organic layer is dried and concentrated in vacuo. The crude product (E) is crystallized from ether and hexane to yield 2 grams of the title compound.
Reaction SMILES: [Br:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([N+:9]([O-:11])=[O:10])[C:7]=1[CH3:8].[CH3:13][OH:14].C[O-].[Na+]>O>[Br:1][C:2]1[C:3]([O:14][CH3:13])=[N:4][CH:5]=[C:6]([N+:9]([O-:11])=[O:10])[C:7]=1[CH3:8]
Reactant: CO
Reactant: Cc1c([N+](=O)[O-])cnc(Cl)c1Br
Agent: C[O-]
Agent: [Na+]
Solvent: O
Product: COc1ncc([N+](=O)[O-])c(C)c1Br
Temperature: 25 °C
Reaction time: 24 h
Yield: 53 %

Procedure:
To a solution of 3-Bromo-2-chloro-4-methyl-5-nitro-pyridine (5.00 g, 19.9 mmol) in anyhdrous Methanol was added a 25% methanolic NaOMe solution (10.7 mL, 2.5 eq). The reaction was stirred at room temperature for 24 hr. The solvent was removed under reduced pressure giving a solid. Water (100 mL) was added to the flask and the flask sonicated for 5 minutes. The precipitate was filtered and washed with water (50 mL) giving a beige powder. The aqueous mother liquor was extracted with EtOAc (1×), the organic washed with brine, and dried. The two solids were combined giving 3-Bromo-2-methoxy-4-methyl-5-nitro-pyridine (2.75 g, 10.6 mmol, 53%). 1H NMR (400 MHz, CDCl3) δ 8.75 (s, 1H), 4.12 (s, 3H), 2.72 (s, 3H).
Reaction SMILES: [OH-].[Na+].[OH:3][CH:4]1[CH2:9][CH2:8][N:7]([C:10]2[N:15]=[C:14]([C:16]([NH:18][C:19]3[C:29]([CH3:30])=[CH:28][C:22]([C:23]([O:25]CC)=[O:24])=[CH:21][C:20]=3[CH3:31])=[O:17])[C:13]([CH3:32])=[CH:12][CH:11]=2)[CH2:6][CH2:5]1.CO>C1COCC1>[OH:3][CH:4]1[CH2:9][CH2:8][N:7]([C:10]2[N:15]=[C:14]([C:16]([NH:18][C:19]3[C:20]([CH3:31])=[CH:21][C:22]([C:23]([OH:25])=[O:24])=[CH:28][C:29]=3[CH3:30])=[O:17])[C:13]([CH3:32])=[CH:12][CH:11]=2)[CH2:6][CH2:5]1
Reactant: CCOC(=O)c1cc(C)c(NC(=O)c2nc(N3CCC(O)CC3)ccc2C)c(C)c1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: Cc1ccc(N2CCC(O)CC2)nc1C(=O)Nc1c(C)cc(C(=O)O)cc1C
Temperature: 40 °C
Yield: 77.1 %

Procedure:
A solution of aqueous 1N NaOH (1.08 ml) is added to a stirred solution of ethyl 4-[[6-(4-hydroxy-1-piperidyl)-3-methyl-pyridine-2-carbonyl]amino]-3,5-dimethyl-benzoate (223 mg, 0.541 mmol) in THF:MeOH (4 ml:2 ml). After heating at 40° C. for 12 hours, the organic solvent is removed under reduced pressure and the semi-solid is dissolved in water and acidified to pH 3 with aqueous 1N HCl. The resulting precipitate is filtered, washed with water, and dried at 40° C. in a vacuum oven for 12 hours to give the title compound as a white solid (160 mg, 77%). Mass spectrum (m/z): 384.2 (M+1).