Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[N:3]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:4]([CH3:7])=[CH:5][CH:6]=1.[Cl-].C([Al+]CC)C.[O:20]1[CH2:25][CH2:24][N:23]([S:26]([C:29]2[CH:37]=[CH:36][CH:35]=[CH:34][C:30]=2[C:31](Cl)=[O:32])(=[O:28])=[O:27])[CH2:22][CH2:21]1>ClCCl>[CH3:7][C:4]1[N:3]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:2]([CH3:1])=[CH:6][C:5]=1[C:31](=[O:32])[C:30]1[CH:34]=[CH:35][CH:36]=[CH:37][C:29]=1[S:26]([N:23]1[CH2:22][CH2:21][O:20][CH2:25][CH2:24]1)(=[O:28])=[O:27]
Reactant: CCOC(=O)Cn1c(C)ccc1C
Reactant: O=C(Cl)c1ccccc1S(=O)(=O)N1CCOCC1
Agent: CC[Al+]CC
Agent: [Cl-]
Solvent: ClCCl
Product: CCOC(=O)Cn1c(C)cc(C(=O)c2ccccc2S(=O)(=O)N2CCOCC2)c1C
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 30.4 %

Procedure:
To a 0° C. solution of ethyl 2-(2,5-dimethyl-1H-pyrrol-1-yl)acetate (0.2 g, 1.10 mmol) in dichloromethane (8.0 mL) was added diethylaluminum chloride (1.66 mL, 1.66 mmol). The reaction was stirred at 0° C. for 15 minutes, after which a solution of 2-(morpholinosulfonyl)benzoyl chloride (0.384 g, 1.32 mmol) was added. The reaction was stirred for 30 minutes at 0° C., then allowed to warm to room temperature, and stirred for 3 hours at this temp. The reaction was quenched with sodium bicarbonate (15 mL), extracted with dichloromethane (3×50 mL), washed with brine, dried (sodium sulfate), filtered, and concentrated. Purification by column chromatography on silica gel using 30 to 100% ethyl acetate in hexanes afforded ethyl 2-(2,5-dimethyl-3-(2-(morpholinosulfonyl)benzoyl)-1H-pyrrol-1-yl)acetate (0.145 g, 0.334 mmol, 30% yield). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.84 (d, 1H), 7.61 (app. t, 1H), 7.55 (dd, 1H), 7.39 (d, 1H), 5.72 (s, 1H), 4.51 (s, 2H), 4.23 (q, 2H), 3.68-3.71 (m, 4H), 3.14-3.17 (m, 4H), 2.44 (s, 3H), 2.07 (s, 3H), 1.29 (t, 3H).
Reaction SMILES: N#N.[C:3]1([C:9]2[O:13][CH:12]=[N:11][C:10]=2[C:14]([OH:16])=O)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C.[CH3:40][O:41][CH2:42][C:43]1[S:47][C:46]([CH2:48][N:49]2[N:53]=[C:52]([NH2:54])[CH:51]=[N:50]2)=[CH:45][CH:44]=1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:40][O:41][CH2:42][C:43]1[S:47][C:46]([CH2:48][N:49]2[N:53]=[C:52]([NH:54][C:14]([C:10]3[N:11]=[CH:12][O:13][C:9]=3[C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=3)=[O:16])[CH:51]=[N:50]2)=[CH:45][CH:44]=1
Reactant: COCc1ccc(Cn2ncc(N)n2)s1
Reactant: O=C(O)c1ncoc1-c1ccccc1
Agent: CN(C)c1ccncc1
Agent: N#N
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCCl
Product: COCc1ccc(Cn2ncc(NC(=O)c3ncoc3-c3ccccc3)n2)s1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of commercially available 5-phenyloxazole-4-carboxylic acid (120 mg, 0.62 mmol) in CH2Cl2 (4.0 mL) was treated at rt with DMAP (19 mg, 0.15 mmol), HOBt (103 mg, 0.74 mmol), EDC (301 mg, 1.54 mmol) and DIPEA (0.5 mL, 2.77 mmol) and the resulting mixture was stirred for 15 min at rt. A solution of 2-((5-(methoxymethyl)thiophen-2-yl)methyl)-2H-1,2,3-triazol-4-amine (131 mg, 0.61 mmol) in CH2Cl2 (8.0 mL) was then added and the reaction mixture was stirred overnight at rt. The mixture was diluted with CH2Cl2 (15.0 mL), the layers were separated and the org. phase was washed with 1N HCl (15.0 mL), water (15.0 mL), followed by brine (15.0 mL) and dried over MgSO4, filtered and the solvents were removed under reduced pressure. Purification of the residue by FC (gradient from 85:15 hept-EA to 70:30 hept-EA) gave the title compound as a white solid. TLC: rf (7:3 hept-EA)=0.2. LC-MS-conditions 07: tR=0.90 min, [M+H]+=396.03
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7]1([C:13]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:14]2[CH2:19][CH2:18][CH:17]([C:20](OCC)=[O:21])[CH2:16][CH2:15]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[OH-].[Na+]>O1CCCC1>[C:7]1([C:13]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:14]2[CH2:19][CH2:18][CH:17]([CH2:20][OH:21])[CH2:16][CH2:15]2)[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: CCOC(=O)C1CCN(C(c2ccccc2)(c2ccccc2)c2ccccc2)CC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCC1CCN(C(c2ccccc2)(c2ccccc2)c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 4 h
Yield: 84 %

Procedure:
To a suspension of 10.6 g of lithium aluminium hydride in 300 ml of dried tetrahydrofuran, a solution of 112 g of ethyl N-triphenylmethyl-4-piperidine-carboxylate in 400 ml of dried tetrahydrofuran was added dropwise under ice-cooling, and the mixture was stirred at room temperature for 4 hours. The reaction mixture was added dropwise with a mixture of tetrahydrofuran and 10% aqueous sodium hydroxide solution under ice-cooling. An insoluble matter was filtered off and washed with tetrahydrofuran. The filtrates were combined and concentrated to give a colorless solid. The colorless solid was washed with methanol to give 84.2 g of colorless crystals. Recrystallization from methanol gave colorless crystals having the melting point of from 92 to 99.5° C.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:15](=[O:16])[C:14]([CH3:18])([CH3:17])[N:13]([CH2:19][C:20]3[CH:25]=[CH:24][N:23]=[C:22](Cl)[CH:21]=3)[C:12]2=[O:27])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:28][C:29]1[CH:30]=[CH:31][C:32]([OH:35])=[N:33][CH:34]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=2OC2C1=CC=C(P(C1C=CC=CC=1)C1C=CC=CC=1)C=2>O1CCOCC1.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:15](=[O:16])[C:14]([CH3:18])([CH3:17])[N:13]([CH2:19][C:20]3[CH:25]=[CH:24][N:23]=[C:22]([NH:28][C:29]4[CH:34]=[N:33][C:32]([OH:35])=[CH:31][CH:30]=4)[CH:21]=3)[C:12]2=[O:27])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: Nc1ccc(O)nc1
Reactant: CC(C)(C)c1ccc(N2C(=O)N(Cc3ccnc(Cl)c3)C(C)(C)C2=O)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC1(C)c2ccc(P(c3ccccc3)c3ccccc3)cc2Oc2cc(P(c3ccccc3)c3ccccc3)ccc21
Solvent: C1COCCO1
Product: CC(C)(C)c1ccc(N2C(=O)N(Cc3ccnc(Nc4ccc(O)nc4)c3)C(C)(C)C2=O)cc1
Temperature: 100 °C
Yield: 5.9 %

Procedure:
To a solution of 0.5 g of 3-(4-tert-butylphenyl)-1-[(2-chloropyridin-4-yl)methyl]-5,5-dimethylimidazolidine-2,4-dione obtained in stage a) of Example 7 in 15 mL of dioxane are successively added, under argon, 285 mg of 5-amino-2-hydroxypyridine, 1.6 g of caesium carbonate, 90 mg of (9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine) [xantphos] and 29 mg of palladium diacetate. The reaction mixture is heated at 100° C. for 1 hour, filtered and concentrated under reduced pressure. The residue is successively purified by chromatography on a column of silica, eluting with a mixture of dichloromethane and methanol (95/5 by volume) followed by HPLC (gradient: water/acetonitrile containing 0.1% formic acid) to give 35 mg of 3-(4-tert-butylphenyl)-1-({2-[(6-hydroxypyridin-3-yl)amino]pyridin-4-yl}methyl)-5,5-dimethylimidazolidine-2,4-dione, the characteristics of which are as follows:
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:17])[C:7]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:8][NH:9]2)=[CH:4][C:3]=1[F:18].C(=O)([O-])[O-].[K+].[K+].Br[CH2:26][CH2:27][OH:28]>CN(C=O)C>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:17])[C:7]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:8][N:9]2[CH2:26][CH2:27][OH:28])=[CH:4][C:3]=1[F:18]
Reactant: OCCBr
Reactant: CCOC(=O)c1c[nH]c2cc(Cl)c(F)cc2c1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1cn(CCO)c2cc(Cl)c(F)cc2c1=O
Temperature: 110 °C
Yield: 67 %

Procedure:
A solution of 8.1 g of 7-chloro-3-ethoxycarbonyl-6-fluoro-4-oxo-1,4-dihydro-quinoline and 8.2 g of potassium carbonate in 70 cm3 of DMF was agitated and heated at 110° C. for 1 hour. After cooling to 60° C., 15 of 2-bromo-ethanol were added to the reaction mixture and it was agitated and heated at 110° C. for 4 hours. After evaporation of the solvent under reduced pressure, 100 cm3 of water were added to the residue and the aqueous mixture was extracted with chloroform (4×100 cm3). The combined organic extracts were washed with water (2×100 cm3), dried over Na2SO4, filtered and then evaporated to dryness. The residue was recrystallised from ethanol (150 cm3). 6.75 g of 7-chloro-6-fluoro-3-ethoxycarbonyl-1-(2-hydroxyethyl)-4-oxo-1,4-dihydroquinoline, m.p. 202° C., were obtained; yield 67%.
Reaction SMILES: [Na].CC1ON=CC=1.ClC1C=C(Cl)C=C(Cl)C=1NN.Cl.[Cl:20][C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[C:23]([Cl:28])[C:22]=1[NH:29][N:30]=[C:31]([CH3:35])[CH2:32][C:33]#[N:34].C[O-].[Na+]>CO.O.CCOCC>[NH2:34][C:33]1[N:29]([C:22]2[C:21]([Cl:20])=[CH:26][C:25]([Cl:27])=[CH:24][C:23]=2[Cl:28])[N:30]=[C:31]([CH3:35])[CH:32]=1
Reactant: CC(CC#N)=NNc1c(Cl)cc(Cl)cc1Cl
Agent: C[O-]
Agent: Cc1ccno1
Agent: Cl
Solvent: CCOCC
Solvent: CO
Solvent: O
Product: Cc1cc(N)n(-c2c(Cl)cc(Cl)cc2Cl)n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 0.51 g (22.0 mmol) of sodium in methanol was added 1.66 g (20.0 mmol) of 5-methylisoxazole. The reaction mixture as refluxed for 8 hours and then stirred overnight at room temperature. Then 4.23 g (20.0 mmol) of 2,4,6-trichlorophenylhydrazine was added and the reaction mixture was again refluxed for 4 hours. A second portion of sodium in methanol was added and reflux was continued for 24 hours. The reaction mixture was taken up with ether and dilute hydrogen chloride. The organic extracts were washed with dilute hydrogen chloride and brine, and then dried with magnesium sulfate and evaporated to give crystals, m.p. 132-134° C. Analysis of this material, particularly two CN bands in the IR spectrum at 2190 cm−1 and 2250 cm−1, revealed it to be a mixture of the cis- and trans-isomers of 1-cyanoacetone-2,4,6-trichlorophenylhydrazone. This material was suspended in methanol and treated with 10.0 mmol of sodium methoxide in 5 mL of methanol. After 5 minutes at room temperature, water was added to crystallize the product which was filtered off and washed well with water. After air drying, the product weighed 2.21 g (40%) and melted at 134.0-135.5° C. Despite the similarity in melting points, the latter material was distinctly different from the former, having an Rf of 0.67 vs. 0.78 for the intermediate on silica gel TLC plates developed with 1:1 hexane ethyl acetate and a distinctly different 300 MHz proton NMR spectrum.
Reaction SMILES: N#N.[F:3][C:4]([C:7]1[O:11][C:10]([CH2:12][N:13]2[N:17]=[C:16]([N+:18]([O-])=O)[CH:15]=[N:14]2)=[CH:9][CH:8]=1)([F:6])[CH3:5].[NH4+].[Cl-]>CCO.O.[Fe]>[F:6][C:4]([C:7]1[O:11][C:10]([CH2:12][N:13]2[N:17]=[C:16]([NH2:18])[CH:15]=[N:14]2)=[CH:9][CH:8]=1)([F:3])[CH3:5]
Reactant: CC(F)(F)c1ccc(Cn2ncc([N+](=O)[O-])n2)o1
Agent: [Fe]
Agent: N#N
Agent: [Cl-]
Solvent: O
Solvent: CCO
Product: CC(F)(F)c1ccc(Cn2ncc(N)n2)o1
Temperature: 85 °C
Reaction time: 0.33 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a mixture of 2-[5-(1,1-difluoro-ethyl)-furan-2-ylmethyl]-4-nitro-2H-[1,2,3]triazole (471 mg, 1.82 mmol), iron powder (309 mg, 5.47 mmol) and NH4Cl (493 mg, 9.12 mmol) in a mixture of EtOH (7.0 mL) and water (3.5 mL) was stirred at 85° C. for 20 min. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (10 mL) was added followed by water (10 mL). The aq. layer was extracted with CH2Cl2 (2×10 mL) and the combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give the title compound as a yellow oil. LC-MS-conditions 02: tR=0.82 min; [M+H+AcCN]+=270.24.
Reaction SMILES: O[C:2]1[C:7]([F:8])=[CH:6][C:5]([Br:9])=[CH:4][C:3]=1[NH:10][C:11](=[O:22])[C:12]1[CH:17]=[C:16]([N+:18]([O-:20])=[O:19])[CH:15]=[CH:14][C:13]=1[F:21].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[N+:18]([C:16]1[CH:17]=[C:12]([C:11]2[O:22][C:2]3[C:7]([F:8])=[CH:6][C:5]([Br:9])=[CH:4][C:3]=3[N:10]=2)[C:13]([F:21])=[CH:14][CH:15]=1)([O-:20])=[O:19]
Reactant: O=C(Nc1cc(Br)cc(F)c1O)c1cc([N+](=O)[O-])ccc1F
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Product: O=[N+]([O-])c1ccc(F)c(-c2nc3cc(Br)cc(F)c3o2)c1

Procedure:
Prepared by the method of Example 15b), from N-(2-hydroxy-3-fluoro-5-bromophenyl)-2-fluoro-5-nitrobenzamide (858 mg, 2.3 mmol) and p-toluenesulfonic acid monohydrate (961 g, 5.1 mmol) the subtitle compound was obtained (475 mg, 58%). 1H NMR (DMSO) δ 8.91(m, 1H), 8.57(m, 1H), 8.06(s, 1H), 7.81(m, 3H).