Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH:19]=[CH:18][N:17]=[CH:16]2)=[CH:11][CH:10]=1)([C:3]([O:5][CH2:6][CH3:7])=[O:4])=[O:2].[N+:20]([O-])([OH:22])=[O:21]>>[C:1]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH:19]=[CH:18][N:17]=[CH:16]2)=[CH:11][C:10]=1[N+:20]([O-:22])=[O:21])([C:3]([O:5][CH2:6][CH3:7])=[O:4])=[O:2]
Reactant: O=[N+]([O-])O
Reactant: CCOC(=O)C(=O)Nc1ccc(-n2ccnc2)cc1
Product: CCOC(=O)C(=O)Nc1ccc(-n2ccnc2)cc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 1 h
Yield: 80 %

Procedure:
1-Ethoxalylamino-4-(1H-imidazol-1-yl)-benzene (16 g; 61.8 mmol) was added gradually to 100 ml nitric acid (d=1.52) at 0° C. Stirring was continued at 0° C. for 1 h, and then the reaction mixture was poured into ice-water to give the title compound (18 g; 80%) as a nitric acid salt. M.p. 180° C. (decomp.).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[NH:12][C:11](=[O:13])[NH:10][C:9]2=[O:14])=[CH:4][CH:3]=1.Cl[CH2:22][C:23]([OH:25])=[O:24].C(O)C.[OH-].[K+].Cl>C(O)C>[C:23]([CH2:22][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[NH:12][C:11](=[O:13])[NH:10][C:9]2=[O:14])=[CH:6][CH:7]=1)([OH:25])=[O:24]
Reactant: O=C(O)CCl
Reactant: O=C1NC(=O)C(c2ccccc2)(c2ccc(O)cc2)N1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)COc1ccc(C2(c3ccccc3)NC(=O)NC2=O)cc1

Procedure:
400 mg of 5-(p-hydroxyphenyl)-5-phenylhydantoin in 4 ml of absolute ethanol was mixed with 140 mg of chloroacetic acid in 3.5 ml of 1 N-potassium hydroxide ethanol solution and then the mixture was refluxed for 22 hours. After cooled, the mixture was acidified with 0.33 ml of 5 N-hydrochloric acid, followed by distillation to remove the ethanol. Then 20 ml of distilled water was added and the pH value was adjusted to 1.0-2.0 with 5 N-hydrochloric acid. The solution obtained was extracted four times with 5 ml of ethyl acetate and dried with anhydrous sodium sulfate. Then it was dissolved in 2 ml of chloroform-methanol (2:1, v/v) solution and the solution was fractionated through a 2.0×40 cm silica gel column. The second fraction was collected. 5-(p-carboxymethoxyphenyl)-5-phenylhydantoin (CMPPH) was obtained by evaporating the second fraction and dried on calcium chloride under vacuo.
Reaction SMILES: [C:1]([C:11]1[N:15](C)[C:14]([CH2:17][C:18]([O:20]C)=[O:19])=[CH:13][CH:12]=1)(=[O:10])[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.[OH-].[Na+].[CH2:24](O)C.C(C1N(C)C(CC(O)=O)=CC=1)(=O)C1C=CC(OC)=CC=1>O>[C:1]([C:11]1[NH:15][C:14]([CH2:17][C:18]([OH:20])=[O:19])=[C:13]([CH3:24])[CH:12]=1)(=[O:10])[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[CH:6][CH:7]=1
Reactant: CCO
Reactant: COC(=O)Cc1ccc(C(=O)c2ccc(OC)cc2)n1C
Agent: COc1ccc(C(=O)c2ccc(CC(=O)O)n2C)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: COc1ccc(C(=O)c2cc(C)c(CC(=O)O)[nH]2)cc1
Yield: 87 %

Procedure:
A solution of 3.00 g. (0.0105 mole) of methyl 5-(ρ-anisoyl)-1-methylpyrrole-2-acetate in 12 ml. (0.012 mole) of 1N sodium hydroxide solution and 5 ml. of 95% ethanol is refluxed for 30 minutes. The solution is diluted with water and the ethanol is evaporated in vacuo. The solution is filtered, and the filtrate acidified with dilute hydrochloric acid. The precipitated solid is collected by filtration, dried and recrystallized from methanol-water to give about 2.4 g. (87% yield) of white-5-(ρ-anisoyl)-1-methylpyrrole-acetic acid, M.P. 170°-171° C.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C:3]1[CH:12]=[C:11]([CH2:13][C:14]([OH:16])=O)[CH:10]=[C:9]2[C:4]=1[CH:5]=[CH:6][CH:7]=[N:8]2.[F:19][C:20]([F:36])([F:35])[C:21]1[CH:30]=[C:29]2[C:24]([CH:25]=[CH:26][CH:27]=[N:28]2)=[C:23]([CH2:31][C:32]([OH:34])=O)[CH:22]=1.[Br:37][C:38]1[C:39]([C:44]2[NH:48][CH:47]=[N:46][N:45]=2)=[C:40]([NH2:43])[S:41][CH:42]=1>>[Br:37][C:38]1[C:39]([C:44]2[NH:48][CH:47]=[N:46][N:45]=2)=[C:40]([NH:43][C:14](=[O:16])[CH2:13][C:11]2[CH:10]=[C:9]3[C:4]([CH:5]=[CH:6][CH:7]=[N:8]3)=[C:3]([C:2]([F:1])([F:18])[F:17])[CH:12]=2)[S:41][CH:42]=1.[Br:37][C:38]1[C:39]([C:44]2[NH:48][CH:47]=[N:46][N:45]=2)=[C:40]([NH:43][C:32](=[O:34])[CH2:31][C:23]2[CH:22]=[C:21]([C:20]([F:19])([F:36])[F:35])[CH:30]=[C:29]3[C:24]=2[CH:25]=[CH:26][CH:27]=[N:28]3)[S:41][CH:42]=1
Reactant: Nc1scc(Br)c1-c1nnc[nH]1
Reactant: O=C(O)Cc1cc(C(F)(F)F)c2cccnc2c1
Reactant: O=C(O)Cc1cc(C(F)(F)F)cc2ncccc12
Product: O=C(Cc1cc(C(F)(F)F)c2cccnc2c1)Nc1scc(Br)c1-c1nnc[nH]1
Product: O=C(Cc1cc(C(F)(F)F)cc2ncccc12)Nc1scc(Br)c1-c1nnc[nH]1

Procedure:
2-(5-(trifluoromethyl)quinolin-7-yl)acetic acid and the mixture of 2-(7-(trifluoromethyl)quinolin-5-yl)acetic acid (28.3 mg, 0.11 mmol) and 4-bromo-3-(4H-1,2,4-triazol-3-yl)thiophen-2-amine (23 mg, 0.094 mmol) were treated according to protocol A. The crude product mixture was purified by HPLC to afford N-(4-bromo-3-(4H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(5-(trifluoromethyl)quinolin-7-yl)acetamide and N-(4-bromo-3-(4H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(7-(trifluoromethyl)quinolin-5-yl)acetamide. LCMS method [13], retention time (min) 10.100 and 10.386; MS(ESI) 482.0 (MH+, 79Br); 1H NMR (300 MHz, CD3OD) δ 9.01 (dd, J=4.3, 1.6 Hz, 1H), 8.62 (d, J=8.4 Hz, 1H), 8.41 (s, 1H), 7.98 (s, 1H), 7.70 (dd, J=8.7, 4.3 Hz, 1H), 4.50 (s, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[C:22]([CH3:23])=[CH:21][C:19]([NH2:20])=[C:18]([CH3:24])[CH:17]=1.C1(C)C=CC=CC=1.C(N(CC)CC)C.Cl[C:40](Cl)([O:42]C(=O)OC(Cl)(Cl)Cl)Cl.[CH3:51][N:52]([CH3:62])[C:53]1[CH:54]=[C:55]([CH:59]=[CH:60][CH:61]=1)[CH:56]([OH:58])[CH3:57]>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[C:22]([CH3:23])=[CH:21][C:19]([NH:20][C:40](=[O:42])[O:58][CH:56]([C:55]2[CH:59]=[CH:60][CH:61]=[C:53]([N:52]([CH3:51])[CH3:62])[CH:54]=2)[CH3:57])=[C:18]([CH3:24])[CH:17]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: CC(O)c1cccc(N(C)C)c1
Reactant: COc1cc2nccc(Oc3cc(C)c(N)cc3C)c2cc1OC
Solvent: ClCCl
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: COc1cc2nccc(Oc3cc(C)c(NC(=O)OC(C)c4cccc(N(C)C)c4)cc3C)c2cc1OC
Temperature: 25 °C
Yield: 45.6 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (110 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-dimethylamino-α-methylbenzyl alcohol (60 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (58 mg, yield 43%).
Reaction SMILES: [C:1](O)(=O)[CH2:2][CH3:3].[CH2:6]([SH:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:15]>C1(C)C=CC=CC=1>[C:1]([S:13][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)(=[S:15])[CH2:2][CH3:3]
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Reactant: CCC(=O)O
Reactant: SCc1ccccc1
Solvent: Cc1ccccc1
Product: CCC(=S)SCc1ccccc1
Temperature: 25 °C
Yield: 50 %

Procedure:
A mixture of propionic acid (0.74 g), benzyl mercaptan (1.24 g) and phosphorus pentasulfide (4.44 g) in toluene (40 ml) was refluxed for 10 h. A dark red color was developed immediately after heating. After the reaction was complete (as monitored by GC-MS), it was cooled to room temperature and purified by a column chromatography packed with neutral alumina, eluting with benzene. Removal of the solvent by distillation gave the desired compound, benzyl dithiopropionate (0.98 g, 50%) without further purification. The structure was confirmed by 1H and 13C-NMR.
Reaction SMILES: [CH2:1]([O:4][C:5]1([CH3:36])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20][N:21]=[N+:22]=[N-:23])[CH:19]=[C:15]3[N:14]=[C:13]([CH3:24])[C:12]=2[C@H:25]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].[CH2:37]([O:40][CH:41]([CH2:44][CH:45]([CH3:47])[CH3:46])[C:42]#[CH:43])[CH:38]=[CH2:39].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>CO>[CH2:37]([O:40][CH:41]([C:42]1[N:23]=[N:22][N:21]([CH2:20][C:18]2[CH:19]=[C:15]3[N:14]=[C:13]([CH3:24])[C:12]([C@H:25]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[C:26]([O:28][CH2:29][CH3:30])=[O:27])=[C:11]([N:8]4[CH2:9][CH2:10][C:5]([O:4][CH2:1][CH:2]=[CH2:3])([CH3:36])[CH2:6][CH2:7]4)[N:16]3[N:17]=2)[CH:43]=1)[CH2:44][CH:45]([CH3:47])[CH3:46])[CH:38]=[CH2:39]
Reactant: C#CC(CC(C)C)OCC=C
Reactant: C=CCOC1(C)CCN(c2c([C@H](OC(C)(C)C)C(=O)OCC)c(C)nc3cc(CN=[N+]=[N-])nn23)CC1
Agent: O=C1O[C@H]([C@@H](O)CO)C([O-])=C1O
Agent: [Na+]
Solvent: CO
Product: C=CCOC(CC(C)C)c1cn(Cc2cc3nc(C)c([C@H](OC(C)(C)C)C(=O)OCC)c(N4CCC(C)(OCC=C)CC4)n3n2)nn1
Temperature: 25 °C
Reaction time: 1 h
Yield: 39.4 %

Procedure:
A mixture of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(azidomethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.179 g, 0.358 mmol), 3-(allyloxy)-5-methylhex-1-yne (0.109 g, 0.717 mmol), Cu(II)SO4.5H2O (8.95 mg, 0.036 mmol) and (+)-sodium L-ascorbate (0.071 g, 0.358 mmol) in MeOH (2 mL) was stirred for 1 h at rt. Then, purified by prep-HPLC to afford (2S)-ethyl 2-(2-((4-(1-(allyloxy)-3-methylbutyl)-1H-1,2,3-triazol-1-yl)methyl)-7-(4-(allyloxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.0921 g, 0.141 mmol, 39.4% yield) as pale yellow paste. LCMS (M+H)=652.7.
Reaction SMILES: Cl.Cl[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.[CH2:11]([N:13]1[C:17]2=[N:18][C:19]3[C:24]([C:25]([NH:26][CH2:27][CH:28]4[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]4)=[C:16]2[CH:15]=[N:14]1)=[CH:23][C:22]([OH:34])=[CH:21][CH:20]=3)[CH3:12].[OH-].[K+]>CS(C)=O>[CH2:11]([N:13]1[C:17]2=[N:18][C:19]3[C:24]([C:25]([NH:26][CH2:27][CH:28]4[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]4)=[C:16]2[CH:15]=[N:14]1)=[CH:23][C:22]([O:34][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1)=[CH:21][CH:20]=3)[CH3:12]
Reactant: ClCCN1CCOCC1
Reactant: CCn1ncc2c(NCC3CCCCC3)c3cc(O)ccc3nc21
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CS(C)=O
Product: CCn1ncc2c(NCC3CCCCC3)c3cc(OCCN4CCOCC4)ccc3nc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 14.7 %

Procedure:
A mixture of DMSO (6 mL), chloroethylmorpholine hydrochloride (1.23 g, 6.6 mmol), 1-ethyl-6-hydroxy-N- (cyclohexylmethyl) -1H-pyrazolo[3,4-b]quinolin-4-amine (2 g, 6.6 mmol) and KOH (1 g) was stirred at room temperature overnight. The reaction mixture was partitioned between CH2Cl2 and water and the CH2Cl2 layer was separated and evaporated. The residue was purified by column chromatography on silica gel eluting with 10% ethanol/ethyl acetate to afford the product as the free base. The free base was recrystallized from hot ethyl acetate/hexane to afford 0.425 g of 1-ethyl-6-[2-(4-morpholinyl)ethoxy]-N-(cyclohexylmethyl)-1H-pyrazolo[ 3,4-b]quinolin-4-amine, as a yellow powder, m.p. 176°-178° C.
Reaction SMILES: [CH2:1]([C:5]1[N:6]=[C:7]([CH3:27])[NH:8][C:9](=[O:26])[C:10]=1[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=2)=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH3:4].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:35][N:36]1[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=2[N:38]=[N:37]1.CN(C)C=O>C(OCC)(=O)C>[N:36]1([CH2:35][N:8]2[C:9](=[O:26])[C:10]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([C:18]4[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=4)=[CH:14][CH:13]=3)=[C:5]([CH2:1][CH2:2][CH2:3][CH3:4])[N:6]=[C:7]2[CH3:27])[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=2[N:38]=[N:37]1
Reactant: ClCn1nnc2ccccc21
Reactant: CCCCc1nc(C)[nH]c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCCCc1nc(C)n(Cn2nnc3ccccc32)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Temperature: 90 °C
Reaction time: 2 h
Yield: 33 %

Procedure:
A mixture of 4′-[(4-butyl-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (1.22 g), potassium carbonate (0.94 g), 1-(chloromethyl)-1H-1,2,3-benzotriazole (0.62 g) and N,N-dimethylformamide (20 mL) was stirred at 90° C. for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.55 g, 33%).
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5](OC)[C:4]=1/[CH:11]=[N:12]/[CH:13]([CH:17]([CH3:19])[CH3:18])[CH:14]([CH3:16])[CH3:15])[CH3:2].[CH:20]([Li])([CH3:22])[CH3:21]>C1COCC1.CCCCC>[CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH:20]([CH3:22])[CH3:21])[C:4]=1/[CH:11]=[N:12]/[CH:13]([CH:17]([CH3:19])[CH3:18])[CH:14]([CH3:16])[CH3:15])[CH3:2]
Reactant: CCc1cccc(OC)c1/C=N/C(C(C)C)C(C)C
Reactant: [Li]C(C)C
Solvent: C1CCOC1
Solvent: CCCCC
Product: CCc1cccc(C(C)C)c1/C=N/C(C(C)C)C(C)C
Temperature: -20 °C
Reaction time: 0.5 h

Procedure:
To a solution of 0.8 g (3.1 mmol) (E)-[1-(2-ethyl-6-methoxy-phenyl)-methylidene]-(1-isopropyl-2-methyl-propyl)-amine (Example 3 a)) in 3 ml dry THF cooled to −20° C. were added 9.62 ml of a 0.7M solution of isopropyl lithium in pentane drop-wise to keep temperature below 0° C. Then the mixture was stirred at −20° C. for further 30 min and the reaction quenched by addition of water. The aqueous phase was extracted with ethyl acetate, the combined extracts washed with brine, dried over Na2SO4, filtered and evaporated. Purification of the crude product by flash chromatography on silica gel with heptane as eluent provided 0.220 g (E)-[1-(2-ethyl-6-isopropyl-phenyl)-methylidene]-(1-isopropyl-2-methyl-propyl)-amine as colourless liquid: MS (ISP): 274.1 (M+H+.).