Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][CH2:2][Si:3]([CH3:13])([CH3:12])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[F:11].[NH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1>C1(C)C(C)=CC=CC=1>[ClH:1].[CH3:12][Si:3]([CH2:2][N:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)([CH3:13])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[F:11]
Reactant: C1CCNCC1
Reactant: C[Si](C)(CCl)Cc1ccccc1F
Solvent: Cc1ccccc1C
Product: C[Si](C)(Cc1ccccc1F)CN1CCCCC1
Product: Cl
Yield: 87.1 %

Procedure:
A solution containing 10.8 g of chloromethyldimethyl-(2-fluorobenzyl)silane and 10.6 g of piperidine in 40 ml of xylene is refluxed for 5.5 hours, then cooled down and washed 5 times with a total of 250 ml of water. After drying the organic phase over anhydrous magnesium sulfate and filtering off the drying agent, the filtrate is evaporated to solvent-free. The oily pale yellow residue is dissolved in 40 ml of methyl ethyl ketone and acidified to pH 4.5 by adding methanolic hydrogen chloride solution. 15 ml of solvent are distilled off from the solution under atmospheric pressure, the crystalline precipitate obtained is filtered at 0° C. and dried to give 13.1 g (87%) of the named product, m.p.: 203°-205° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)=[CH:4][C:3]=1[N:15]1[C:19](=[O:20])[C:18]2[CH2:21][CH2:22][CH2:23][CH2:24][C:17]=2[C:16]1=[O:25].[C:26]1([CH2:32][CH2:33][NH2:34])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C1C=CC=CC=1.CCCCCC>[F:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH:10]2[CH2:11][CH2:12][CH2:13][CH2:14]2)=[CH:4][C:3]=1[NH:15][C:19](=[O:20])[C:18]1[CH2:21][CH2:22][CH2:23][CH2:24][C:17]=1[C:16]([NH:34][CH2:33][CH2:32][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:25]
Reactant: O=C1C2=C(CCCC2)C(=O)N1c1cc(OC2CCCC2)c(Cl)cc1F
Reactant: NCCc1ccccc1
Solvent: c1ccccc1
Solvent: CCCCCC
Product: O=C(NCCc1ccccc1)C1=C(C(=O)Nc2cc(OC3CCCC3)c(Cl)cc2F)CCCC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 63 %

Procedure:
N-(2-Fluoro-4-chloro-5-cyclopentyloxyphenyl)-3,4,5,6-tetrahydrophthalimide (1.00 g, 2.75 mmol), β-phenylethylamine (0.333 g, 2.75 mmol), and benzene (8 ml)/hexane (12 ml) as a solvent were placed into a round bottom flask (50 cc) and stirred for 30 minutes at room temperature. After completion of the reaction, the solvent was distilled off under reduced pressure, and the precipitated crystals were isolated by filtration. The crystals were washed with hexane and dried to obtain N-(2-fluoro-4-chloro-5-cyclopentyloxyphenyl)-N'-(2-phenylethyl)-3,4,5,6-tetrahydrophthalamide as white crystals (0.840 g, 62.9% yield).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]3[CH:18]=[C:17]([CH3:19])[C:16](=[O:20])[C:8]4[CH:9]=[C:10]([OH:15])[CH:11]=[C:12]([C:13]=2[CH:14]=1)[C:7]3=4.C(=O)([O-])[O-].[K+].[K+].Cl.[N:28]1[CH:33]=[CH:32][CH:31]=[C:30]([CH2:34]Cl)[CH:29]=1>CS(C)=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]3[CH:18]=[C:17]([CH3:19])[C:16](=[O:20])[C:8]4[CH:9]=[C:10]([O:15][CH2:34][C:30]5[CH:29]=[N:28][CH:33]=[CH:32][CH:31]=5)[CH:11]=[C:12]([C:13]=2[CH:14]=1)[C:7]3=4
Reactant: Cc1cn2c3ccc(Br)cc3c3cc(O)cc(c1=O)c32
Reactant: ClCc1cccnc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: Cc1cn2c3ccc(Br)cc3c3cc(OCc4cccnc4)cc(c1=O)c32
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 60.4 %

Procedure:
10-bromo-2-hydroxy-5-methyl-4H-pyrido[3,2,1-jk]carbazole-4-one (350 mg) obtained in Example 49 was suspended in dimethyl sulfoxide (14 ml), and potassium carbonate (440 mg) was added to the suspension. The mixture was stirred at room temperature for 30 minutes and 3-picolylchloride hydrochloride (190 mg) was added to the mixture. The mixture was stirred at room temperature for 12 hours, and the reaction mixture was poured into ice water (500 ml). The crystals precipitated were recovered by filtration. The resulting crude crystals were washed with methanol and ether in succession, and recovered by filtration to obtain the title compound (270 mg, 60%).
Reaction SMILES: C1(CO[C:9]([NH:11][C@H:12]([C:17]([NH:19][C@H:20]([CH2:24][OH:25])[CH:21]([CH3:23])[CH3:22])=[O:18])[CH2:13][CH:14]([CH3:16])[CH3:15])=[O:10])C=CC=CC=1.O.C(=O)([O-])[O-].[Na+].[Na+].[O:33]1[CH:37]=[CH:36][CH:35]=[C:34]1C(Cl)=O>CO.C(OCC)(=O)C.[C].[Pd]>[O:33]1[CH:37]=[CH:36][CH:35]=[C:34]1[C:9]([NH:11][C@H:12]([C:17]([NH:19][C@H:20]([CH2:24][OH:25])[CH:21]([CH3:22])[CH3:23])=[O:18])[CH2:13][CH:14]([CH3:15])[CH3:16])=[O:10]
Reactant: CC(C)C[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@H](CO)C(C)C
Reactant: O=C(Cl)c1ccco1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CO
Product: CC(C)C[C@H](NC(=O)c1ccco1)C(=O)N[C@H](CO)C(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 86.3 %

Procedure:
30 mg of 10% palladium-carbon was added to a solution of 350 mg (1 mmol) of N—[N-[(phenylmethoxy)carbonyl]-L-leucyl]-L-valinol obtained in Reference Example 184 in 10 ml of methanol, and the mixture was stirred under a hydrogen atmosphere at room temperature overnight. After the reaction solution was filtered, the filtrate was concentrated under reduced pressure. 10 ml of ethyl acetate, 10 ml of water and further 159 mg (1.5 mmol) of sodium carbonate were added to the residue. Under ice-cooling, a solution of 131 mg (1 mmol) of 2-furancarbonyl chloride in 3 ml of ethyl acetate was added to the mixture solution. The reaction solution was returned to room temperature and was stirred overnight. The aqueous layer of the reaction solution was separately collected and extracted with ethyl acetate. The organic layer was combined and after it was washed with a 10% potassium hydrogensulfate and then saturated brine, it was dried with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and ether was added to the residue to wash the crystal to obtain 268 mg (86%) of the title compound.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:20]([OH:22])=O)[CH2:10][C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.C(Cl)(=O)OCC.[NH2:36][C:37]1[S:38][CH:39]=[N:40][N:41]=1>C(Cl)(Cl)Cl>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:20]([NH:36][C:37]1[S:38][CH:39]=[N:40][N:41]=1)=[O:22])[CH2:10][C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: Nc1nncs1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)O
Agent: CCOC(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: CC(C)(C)OC(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)Nc1nncs1
Yield: 84.6 %

Procedure:
Using the same procedure as in Example 1(i), 10 g of N-t-butoxycarbonyl-L-tryptophan, 3.3 g of triethylamine, 3.5 g of ethyl chlorocarbonate and 3.3 g of 2-amino-1,3,4-thiadiazole were reacted in 150 ml of chloroform to obtain 10.7 g (yield: 84%) of 2-(N-t-butoxycarbonyl-L-tryptophanylamino)-1,3,4-thiadiazole as light yellow powder of mp: 98°-101° C. (dec.) and [α]D20 : +41.0° (C=1.0, MeOH).
Reaction SMILES: C(N(CC)CC)C.[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].Cl[C:22]1[S:26][N:25]=[C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[F:33])[N:23]=1.O>CN(C)C=O>[F:33][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[C:24]1[N:23]=[C:22]([N:18]2[CH2:19][CH2:20][N:15]([C:13]([O:12][C:8]([CH3:11])([CH3:9])[CH3:10])=[O:14])[CH2:16][CH2:17]2)[S:26][N:25]=1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: Fc1ccccc1-c1nsc(Cl)n1
Solvent: CCN(CC)CC
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCN(c2nc(-c3ccccc3F)ns2)CC1
Yield: 65.5 %

Procedure:
Triethylamine (14.7 ml, 105 mmol) was added to a solution of 1-(tert-butoxycarbonyl)piperazine (5.64 g, 26.3 mmol) and 5-chloro-3-(2-fluorophenyl)-1,2,4-thiadiazole (4.89 g, 26.3 mmol) in N,N-dimethylformamide (100 ml), the mixture was stirred was stirred at room temperature for 30 minutes, the reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water, and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was recrystallized from a mixed solvent of hexane and ethyl acetate to give 6.28 g (65.6%) of the desired product as a crystal.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:8]=[CH:9][CH:10]=1)[NH2:7])([O-:3])=[O:2].[CH3:11][N:12]([CH3:22])[C:13]1[CH:14]=[C:15]([CH:19]=[CH:20][CH:21]=1)[C:16](Cl)=[O:17]>C(Cl)Cl.CN(C)C1C=CN=CC=1.C(N(CC)CC)C>[N+:1]([C:4]1[CH:5]=[C:6]([NH:7][C:16](=[O:17])[C:15]2[CH:19]=[CH:20][CH:21]=[C:13]([N:12]([CH3:11])[CH3:22])[CH:14]=2)[CH:8]=[CH:9][CH:10]=1)([O-:3])=[O:2]
Reactant: Nc1cccc([N+](=O)[O-])c1
Reactant: CN(C)c1cccc(C(=O)Cl)c1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CN(C)c1cccc(C(=O)Nc2cccc([N+](=O)[O-])c2)c1
Temperature: 25 °C
Reaction time: 72 h
Yield: 99.9 %

Procedure:
3-Nitroaniline (3.84 g) in methylene chloride (50 ml) was added dropwise to an ice-cooled solution of 3-dimethylaminobenzoyl chloride (9.74 g crude weight) and 4-dimethylaminopyridine (308 mg) in methylene chloride (30 ml) and triethylamine (8.8 ml). The reaction was stirred at ambient temperature for 72 hours and then partitioned between methylene chloride and saturated sodium bicarbonate. The organic phase was then washed with brine, dried over magnesium sulphate, filtered and evaporated to dryness affording N-(3-nitrophenyl)-3-dimethylaminobenzamide as a solid (8.64 g, 99.9%); NMR (CDCl3) 3.02 (s, 6H), 6.9 (m, 1H), 7.09 (s, 1H), 7.25 (m, 1H), 7.35 (t, 1H), 7.53 (t, 1H), 7.99 (m, 1H), 8.05 (broad s, 1H), 8.1 (m, 1H), 8.5 (m, 1H); m/s: M+H+ 286.
Reaction SMILES: [CH3:1][C:2]1([CH3:10])[O:9][C:7](=[O:8])[CH2:6][C:4](=[O:5])O1.[C:11](Cl)(O)=O.[CH2:15]1[CH2:18][CH2:17][CH2:16]1>ClCCl.N1C=CC=CC=1>[CH:15]1([C:4](=[O:5])[CH2:6][C:7]([O:9][C:2]([CH3:1])([CH3:10])[CH3:11])=[O:8])[CH2:18][CH2:17][CH2:16]1
Reactant: CC1(C)OC(=O)CC(=O)O1
Reactant: C1CCC1
Reactant: O=C(O)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)CC(=O)C1CCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 53.7 %

Procedure:
In a mixture of 100 ml of dichloromethane and 15 ml of pyridine was dissolved 12.2 g of meldrum's acid. Under cooling with ice, 10.0 g of cyclobutane carboxychloride was added dropwise to the solution, followed by stirring under room temperature for 2 hours. The solvent was removed under reduced pressure and to the residue was added water. The mixture was extracted with ethyl acetate. The extract was washed with 1N hydrochloric acid and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. The residue was dissolved in 100 ml of tert-butanol and the solution was heated under reflux for 5 hours. The solvent was removed under reduced pressure and the residue was subjected to column chromatography using 100 g of silica gel. The oily titled compound (7.8 g) was obtained from a chloroform eluate fraction.
Reaction SMILES: [CH:1](O)=[O:2].[C:4]([O:7][C:8](=[O:10])C)(=[O:6])C.[CH3:11][O:12][C:13]1[CH:14]=[C:15]([C:19]2[CH:28]=[C:27]([NH2:29])[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([NH2:30])[CH:25]=3)[N:20]=2)[CH:16]=[CH:17][CH:18]=1.CCOCC>C1COCC1>[CH:4]([O:7][CH:8]=[O:10])=[O:6].[NH2:29][C:27]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([NH:30][CH:1]=[O:2])[CH:25]=2)[N:20]=[C:19]([C:15]2[CH:16]=[CH:17][CH:18]=[C:13]([O:12][CH3:11])[CH:14]=2)[CH:28]=1
Reactant: CC(=O)OC(C)=O
Reactant: O=CO
Reactant: COc1cccc(-c2cc(N)c3cc(N)ccc3n2)c1
Solvent: C1CCOC1
Solvent: CCOCC
Product: COc1cccc(-c2cc(N)c3cc(NC=O)ccc3n2)c1
Product: O=COC=O
Temperature: 50 °C
Yield: 75.1 %

Procedure:
Formic anhydride was prepared by placing 260 mg (5.66 mmoles) of formic acid into a dry 100 mL round-bottom flask equipped with a condenser, magnetic stirrer and a nitrogen inlet. The flask was cooled with an ice bath and then 470 mg (4.61 mmoles) of acetic anhydride was added. The stirring solution was then gently warmed to 50° C. with an oil bath for 2 hrs. After this time the reaction was cooled, and 25 mL of dry THF was added followed by the addition of 1.0 g (3.77 mmoles) of 2-(3-methoxyphenyl)-4,6-quinolinediamine as a solution in 10 mL of dry THF. The mixture was then heated to reflux for 2 hrs. At the end of this time the reaction was cooled and ether was added. The solids which formed were then collected by filtration and washed with ether. The solids were then dissolved in ethyl acetate and 5% NaOH solution, the layers separated and the organic layer dried over Na2SO4, filtered and concentrated to give 830 mg (75%) of the desired product. This product was used without further purification.