Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[C:11]2[NH:10][C:9](=[O:12])[C@@H:8]3[CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][C@@H:7]3[C:6]=2[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:26]>CN(C=O)C.C1COCC1.[Cl-].[Na+].O>[CH3:26][N:10]1[C:11]2[C:2]([CH3:1])=[CH:3][CH:4]=[CH:5][C:6]=2[C@H:7]2[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13][C@H:8]2[C:9]1=[O:12]
Reactant: CI
Reactant: Cc1cccc2c1NC(=O)[C@@H]1CN(C(=O)OC(C)(C)C)C[C@H]21
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: Cc1cccc2c1N(C)C(=O)[C@@H]1CN(C(=O)OC(C)(C)C)C[C@H]21
Temperature: 25 °C
Reaction time: 1 h
Yield: 89.5 %

Procedure:
To a solution of (±)-cis tert-butyl 6-methyl-4-oxo-3,3a,4,5-tetrahydro-1H-pyrrolo[3,4-c]quinoline-2(9bH)-carboxylate (0.5 g, 1.66 mmol) in 10 mL of DMF and 5 mL of THF was added sodium hydride (0.2 g, 60% dispersion in mineral oil, 5.0 mmol). The mixture was allowed to stir at ambient temperature for 1 h and then there was added iodomethane (0.25 mL, 4.0 mmol). The reaction was allowed to stir at ambient temperature for 18 h. The reaction mixture was poured into brine and extracted with ethyl acetate. The organics were washed with water and brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography to afford 0.47 g (90%) of (±)-cis tert-butyl 5,6-dimethyl-4-oxo-3,3a,4,5-tetrahydro-1H-pyrrolo[3,4-c]quinoline-2(9bH)-carboxylate.
Reaction SMILES: [CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[C:13]([F:14])=[CH:12][N:11]=[C:10]3[NH:15][CH:16]=[CH:17][C:9]=23)[C:5]([C:18]2[CH:23]=[CH:22][C:21]([N+:24]([O-])=O)=[CH:20][CH:19]=2)=[N:4]1)[CH3:2].[Sn].Cl>C(O)C>[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[C:13]([F:14])=[CH:12][N:11]=[C:10]3[NH:15][CH:16]=[CH:17][C:9]=23)[C:5]([C:18]2[CH:23]=[CH:22][C:21]([NH2:24])=[CH:20][CH:19]=2)=[N:4]1)[CH3:2]
Reactant: CCn1cc(-c2c(F)cnc3[nH]ccc23)c(-c2ccc([N+](=O)[O-])cc2)n1
Agent: Cl
Agent: [Sn]
Solvent: CCO
Product: CCn1cc(-c2c(F)cnc3[nH]ccc23)c(-c2ccc(N)cc2)n1
Temperature: 70 °C

Procedure:
To a suspension of 4-[1-ethyl-3-(4-nitrophenyl)-1H-pyrazol-4-yl]-5-fluoro-1H-pyrrolo[2,3-b]pyridine (0.655 mmol) in ethanol (3.5 mL) was added tin(0) powder (3.28 mmol) and 6N aqueous hydrochloric acid (3.5 mL) and the mixture was heated to 70° C. for 1 h. The reaction mixture was allowed to cool to room temperature, filtered through a pad of celite. The filtrate was diluted with ethyl acetate (10 mL) and washed with 1N sodium hydroxide (5 m L). The aqueous layer was extracted with ethyl acetate (3×10 mL) and the combined extracts were dried over sodium sulfate, filtered through a pad of celite and concentrated under reduced pressure to give the title compound as a yellow solid which was used without further purification. ESMS [M+H]+: 322
Reaction SMILES: [C:1]1([S:7]([CH2:10][C@H:11]([C:13]2([OH:18])[CH2:17][CH2:16][CH2:15][CH2:14]2)[CH3:12])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C=CN=C1.Cl[Si:25]([CH2:30][CH3:31])([CH2:28][CH3:29])[CH2:26][CH3:27]>CN(C)C=O>[C:1]1([S:7]([CH2:10][C@H:11]([C:13]2([O:18][Si:25]([CH2:30][CH3:31])([CH2:28][CH3:29])[CH2:26][CH3:27])[CH2:17][CH2:16][CH2:15][CH2:14]2)[CH3:12])(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: C[C@H](CS(=O)(=O)c1ccccc1)C1(O)CCCC1
Reactant: CC[Si](Cl)(CC)CC
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC[Si](CC)(CC)OC1([C@H](C)CS(=O)(=O)c2ccccc2)CCCC1
Temperature: 0 °C
Yield: 123.9 %

Procedure:
To a solution of 6a (2.40 g, 8.94 mmol) and imidazole (1.22 g, 17.9 mmol) in N,N-dimethylformamide (20 mL) was added chlorotriethylsilane (2.2 mL, 13.1 mmol) in one portion. The mixture was stirred at ambient temperature for 3d. The mixture was poured into ice water, and extracted with diethyl ether. The combined organic layers were washed with water and brine, and dried over sodium sulfate. Filtration and concentration gave 4.24 g of an oily material, which was purified by column chromatography (silica gel 40 g, ethyl acetate in n-hexane, 10%) to give 3.67 g (quantitative) of 7a, as a colorless oil.
Reaction SMILES: [CH2:1]1[CH2:38][O:37][C:3]([CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])([CH2:4][CH2:5][C@H:6]2[C@H:10]([O:11][CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[CH2:9][C@H:8]([OH:18])[C@@H:7]2[CH2:19]/[CH:20]=[CH:21]\[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([OH:29])=[O:28])[O:2]1.[CH2:39]1[CH2:49]CN2C(=NCCC2)C[CH2:40]1.C(I)(C)C>C(#N)C>[CH2:38]1[CH2:1][O:2][C:3]([CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])([CH2:4][CH2:5][C@H:6]2[C@H:10]([O:11][CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[CH2:9][C@H:8]([OH:18])[C@@H:7]2[CH2:19]/[CH:20]=[CH:21]\[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([O:29][CH:39]([CH3:49])[CH3:40])=[O:28])[O:37]1
Reactant: C1CCC2=NCCCN2CC1
Reactant: CCCCCCCC1(CC[C@@H]2[C@@H](C/C=C\CCCCCC(=O)O)[C@@H](O)C[C@H]2OC2CCCCO2)OCCO1
Solvent: CC(C)I
Solvent: CC#N
Product: CCCCCCCC1(CC[C@@H]2[C@@H](C/C=C\CCCCCC(=O)OC(C)C)[C@@H](O)C[C@H]2OC2CCCCO2)OCCO1

Procedure:
The compound (74) (1.68 g) was esterified in the conventional procedure with 1,8-diazabicyclo[5.4.0]-7-undecene (DBU, 0.78 ml) and isopropyl iodide (0.35 ml) in acetonitrile (15 ml). The residue was subjected to silicagel column chromatography to give the titled compound (75).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]1[CH:12]=[CH:13][C:14]([C:16]([OH:18])=[O:17])=[CH:15][N:6]1[C:5]2=[O:19].[OH-:20].[Na+]>O>[C:5]([C:4]1[CH:3]=[C:2]([CH3:1])[CH:11]=[CH:10][C:9]=1[NH:8][C:7]1[CH:12]=[CH:13][C:14]([C:16]([OH:18])=[O:17])=[CH:15][N:6]=1)([OH:19])=[O:20]
Reactant: Cc1ccc2nc3ccc(C(=O)O)cn3c(=O)c2c1
Reactant: [OH-]
Agent: [Na+]
Solvent: O
Product: Cc1ccc(Nc2ccc(C(=O)O)cn2)c(C(=O)O)c1

Procedure:
A solution of 10.0 g (39.4 mmol) of 2-methyl-11-oxo-11H-pyrido[2,1-b]quinazoline-8-carboxylic acid and 78.8 ml of 1 N. NaOH in 500 ml of H2O was heated at reflux for 16 hours. The reaction mixture was evaporated to give a white powder which was triturated with hot EtOH giving the analytical sample upon filtration and drying; yield, 8.25 g (66.5%) mp 348.5° dec.
Reaction SMILES: [CH3:1][N:2]([CH3:6])[CH2:3][CH2:4][NH2:5].[CH2:7]([O:14][C:15](=[O:28])[C:16]1[CH:21]=[CH:20][C:19]([CH2:22]OS(C)(=O)=O)=[CH:18][CH:17]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>CN(C=O)C>[CH2:7]([O:14][C:15](=[O:28])[C:16]1[CH:17]=[CH:18][C:19]([CH2:22][NH:5][CH2:4][CH2:3][N:2]([CH3:6])[CH3:1])=[CH:20][CH:21]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: CS(=O)(=O)OCc1ccc(C(=O)OCc2ccccc2)cc1
Reactant: CN(C)CCN
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CN(C)CCNCc1ccc(C(=O)OCc2ccccc2)cc1

Procedure:
N,N-Dimethylethylenediamine (0.90 mL, 8.2 mmol) was added to a solution of 4-methanesulfonyloxymethylbenzoic acid benzyl ester (Reference Compound No. 6-1, 2.3 g, 7.2 mmol) and triethylamine (3.0 mL, 22 mmol) in DMF (10 mL), and then the reaction mixture was stirred at room temperature for 2 hours. Saturated aqueous sodium hydrogen carbonate solution (0.15 L) was added to the reaction solution, and the whole was extracted with chloroform (0.10 L) three times. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure to give 1.2 g of mixture including the title reference compound as yellow oil.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH2:7](Cl)[CH:8]=[CH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C(O)(C)C>[CH2:7]([N:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1)[CH:8]=[CH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: ClCC=Cc1ccccc1
Reactant: C1CNCCN1
Solvent: CC(C)O
Product: C(=Cc1ccccc1)CN1CCNCC1
Temperature: 70 °C
Yield: 56 %

Procedure:
Absolute piperazine (217 g, 2.5 moles) was dissolved in 1 liter of isopropanol and 72.6 g of cinnamyl chloride (0.5 moles) were added dropwise gradually at room temperature without mixing. After the completion of dropwise addition, it was heated at 70° C for 3 hrs. with mixing. After the solvent was distilled away, the reaction mixture was dissolved in 500 ml of chloroform and then washed with sodium hydroxide and water. Subsequently, it was dried over potassium carbonate and then was filtered. Chloroform was distilled away in vacuo. By Subliming the mixture obtained, piperazine was removed and then the residues were distiled to obtain N-cinnamyl piperazine. The product was crystallized and then was recrystallized from n-hexane. Boiling point of the product was 162°-165° C (4 mmHg). Melting point was 31°-33° C and the yield was 56%.
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[CH:4]=1.[NH2:11][C:12]1[S:13][CH:14]=[CH:15][N:16]=1.N1C2C(=CC=CC=2)C=C1.[NH:26]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:28]([C:35](OC)=[O:36])=[CH:27]1>>[S:13]1[CH:14]=[CH:15][N:16]=[C:12]1[NH:11][C:35]([C:28]1[C:29]2[C:34](=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:26]([CH2:2][C:3]2[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[CH:4]=2)[CH:27]=1)=[O:36]
Reactant: COc1cccc(CBr)c1
Reactant: Nc1nccs1
Reactant: COC(=O)c1c[nH]c2ccccc12
Agent: c1ccc2[nH]ccc2c1
Product: COc1cccc(Cn2cc(C(=O)Nc3nccs3)c3ccccc32)c1

Procedure:
R5X=1-Bromomethyl-3-methoxy-benzene; NH2A=2-aminothiazole; Indole starting material=methyl indole 3-carboxylate
Reaction SMILES: N#N.[CH3:3][C:4]1([C:9]2[S:13][C:12]([CH2:14][OH:15])=[N:11][CH:10]=2)[O:8][CH2:7][CH2:6][O:5]1.CCN(CC)CC.[S:23](Cl)([CH3:26])(=[O:25])=[O:24]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:3][C:4]1([C:9]2[S:13][C:12]([CH2:14][O:15][S:23]([CH3:26])(=[O:25])=[O:24])=[N:11][CH:10]=2)[O:8][CH2:7][CH2:6][O:5]1
Reactant: CS(=O)(=O)Cl
Reactant: CC1(c2cnc(CO)s2)OCCO1
Agent: CN(C)c1ccncc1
Agent: N#N
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC1(c2cnc(COS(C)(=O)=O)s2)OCCO1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of [5-(2-methyl-[1,3]dioxolan-2-yl)-thiazol-2-yl]-methanol (560 mg, 2.78 mmol) in dry CH2Cl2 (5.0 mL) was treated at 0° C. with Et3N (0.50 mL, 3.60 mmol) followed by DMAP (34 mg, 0.28 mmol) and Ms-Cl (0.28 mL, 3.51 mmol). After stirring at 0° C. for 1 h, the reaction mixture was quenched with water (10 mL), extracted with CH2Cl2 (10 mL) and the combined org. extracts were dried over Na2SO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (5:1 to 2:1 hept-EA) gave the title compound as a brown oil. LC-MS-conditions 01: tR=0.77 min; [M+H]+=279.88.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([N:11]2[CH2:15][CH2:14][C@@H:13]([OH:16])[CH2:12]2)[S:9][CH:10]=1)=[O:5])[CH3:2].[CH3:17][S:18](Cl)(=[O:20])=[O:19].C(N(CC)CC)C.C(O)C>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([N:11]2[CH2:15][CH2:14][C@@H:13]([O:16][S:18]([CH3:17])(=[O:20])=[O:19])[CH2:12]2)[S:9][CH:10]=1)=[O:5])[CH3:2]
Reactant: CS(=O)(=O)Cl
Reactant: CCOC(=O)c1csc(N2CC[C@@H](O)C2)n1
Solvent: CCN(CC)CC
Solvent: CCO
Solvent: ClCCl
Product: CCOC(=O)c1csc(N2CC[C@@H](OS(C)(=O)=O)C2)n1
Reaction time: 1 h
Yield: 78 %

Procedure:
To a solution of (3R)-1-(4-ethoxycarbonyl-1,3-thiazol-2-yl)-3-hydroxypyrrolidine (970 mg, 4.00 mmol) (obtained as described in Reference Example 18(2)) in methylene chloride (30 ml) were added methanesulfonyl chloride (1.24 ml, 16.0 mmol) and triethylamine (2.24 ml, 16.0 mmol) in an ice bath, and then the mixture was stirred for 1 hour. After checking the completion of the reaction, ethanol (0.81 ml) was added thereto and then the resulting mixture was stirred at room temperature for 30 minutes. The reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate solution. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using toluene:acetonitrile (4:1→1:1) as the eluant to afford (3R)-1-(4-ethoxycarbonyl-1,3-thiazol-2-yl)-3-methanesulfonyloxypyrrolidine (1.00 g, yield 78%) as a pale yellow solid.