Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[C:11]([O:30][CH2:31][CH2:32][OH:33])=[N:12][N:13]([CH3:29])[C:14]=3[NH:15][S:16]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([CH3:28])([CH3:27])[CH3:26])=[CH:21][CH:20]=3)(=[O:18])=[O:17])=[CH:9][C:4]=2[O:3][CH2:2]1.C[OH:35]>>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[C:11]([O:30][CH2:31][CH2:32][OH:33])=[N:12][N:13]([CH3:29])[C:14]=3[NH:15][S:16]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([CH3:28])([CH3:26])[CH2:27][OH:35])=[CH:21][CH:20]=3)(=[O:18])=[O:17])=[CH:9][C:4]=2[O:3][CH2:2]1
Reactant: CO
Reactant: Cn1nc(OCCO)c(-c2ccc3c(c2)OCO3)c1NS(=O)(=O)c1ccc(C(C)(C)C)cc1
Product: Cn1nc(OCCO)c(-c2ccc3c(c2)OCO3)c1NS(=O)(=O)c1ccc(C(C)(C)CO)cc1
Reaction time: 48 h

Procedure:
Amycolata autotrophica ATCC35203 maintained on a quarter strength ATCC172 agar slope was inoculated as a loopful of spores into a 300 ml Erlenmeyer flasks each containing 50 ml of MY inoculum medium. This was allowed to incubate for 2 days at 28° C., 200 rpm on an Infors Multitron™ Shaker with 1″ throw. Two mls of this inoculum was then transferred to each of twenty 300 ml Erlenmeyer flask containing 50 ml of MY production medium and incubated under the same conditions for a further 24 hours. At this point 5 mg of N-[4-(1,3-benzodioxol-5-yl)-3-(2-hydroxyethoxy)-1-methyl-1H-pyrazol-5-yl]-4-(tert-butyl)benzenesulfonamide (GB Patent Application No 9917858.4) dissolved in 0.5 ml of methanol was added to each of the flasks and the fermentation allowed to continue under the same conditions for a further 96 hours. Each flask was then extracted with 200 mls of ethyl acetate and the combined ethyl acetate solubles concentrated to dryness to give a gum solid.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[O:9][CH:8]=[CH:7][C:6]=2[CH:10]=1.[Br-].[CH:12]1([Zn+])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1>C1COCC1.C(OCC)(=O)C.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH:12]1([C:2]2[CH:3]=[CH:4][C:5]3[O:9][CH:8]=[CH:7][C:6]=3[CH:10]=2)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1
Reactant: Brc1ccc2occc2c1
Reactant: [Zn+]C1CCCCC1
Agent: CC(C)(C)[P]([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C(C)(C)C
Agent: [Br-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: c1cc2cc(C3CCCCC3)ccc2o1
Temperature: 100 °C
Yield: 42.5 %

Procedure:
5-bromobenzofuran (500 mg, 2.55 mmol) was dissolved in a THF solution of cyclohexyl zinc(II) bromide (0.5M, 15 mL, 7.40 mmol) in a microwave reaction tube. Pd(PtBu3)2 (65 mg, 0.128 mmol, 0.05 eq.) was added to this solution. The mixture was purged with N2 gas for 3-5 min and heated at 100° C. for 30 min under microwave irradiation. Upon completion of the reaction, the reaction mixture was diluted with ethyl acetate, washed with 1N HCl aqueous solution, brine, filtered through Celite. The filtrate was dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (ISCO system, 5% EtOAc in hexanes) to give 0.217 g desired product (43% yield): 1H NMR (400 MHz, CDCl3) δ 7.57 (d, 1H), 7.41 (d, 2H), 7.15 (d, 1H), 6.72 (d, 1H), 2.58 (m, 1H), 1.92-1.74 (m, 4H), 1.51-1.35 (m, 4H), 1.31-1.25 (m, 2H).
Reaction SMILES: [CH2:1]([SH:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[OH-].[K+:11].[C:12](=[S:14])=[S:13]>>[CH2:1]([S:9][C:12]([S-:14])=[S:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[K+:11]
Reactant: S=C=S
Reactant: CCCCCCCCS
Agent: [K+]
Agent: [OH-]
Product: CCCCCCCCSC(=S)[S-]
Temperature: 0 °C
Reaction time: 1 h
Yield: 96 %

Procedure:
438.9 g (520.6 ml, 3 moles) of 1-octanethiol were refluxed (with stirring) for about 1 hour with 66 g. (1 mole 85% purity) potassium hydroxide flakes. 72.5 ml (91.33 g., 1.2 moles) of CS2 were then added (dropwise) with stirring to the mixture which had been cooled to 0° C. in an ice-water bath. The mixture was stirred for about 1 hour after addition was complete, and then allowed to warm to room temperature. The resulting white solid precipitate was filtered, thoroughly washed with anhydrous ethyl ether, and dried overnight in a vacuum oven at 35° C. 250.1 g. of potassium octylthioxanthate were obtained (96% yield).
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10](=[O:20])[C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)=[N:12]O)=[CH:9][C:4]=2[O:3][CH2:2]1.[ClH:21].[H][H]>C(O)C.O.[Pd]>[ClH:21].[ClH:21].[NH2:12][CH:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1)[C:10]([C:8]1[CH:7]=[CH:6][C:5]2[O:1][CH2:2][O:3][C:4]=2[CH:9]=1)=[O:20]
Reactant: O=C(C(=NO)c1ccccn1)c1ccc2c(c1)OCO2
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: CCO
Solvent: O
Product: NC(C(=O)c1ccc2c(c1)OCO2)c1ccccn1
Yield: 59 %

Procedure:
1-Benzo[1,3]dioxol-5-yl-2-pyridin-2-yl-ethane-1,2-dione 2-oxime (2 g, 7.75 mmol) was dissolved in ethanol (100 ml) and hydrochloric acid (2 ml of a 36% solution in water) was added. Palladium on charcoal catalyst (0.5 g) was added and the reaction mixture was stirred under a positive pressure of hydrogen for 1.5 hours. The catalyst was removed by filtration through Kieselguhr and the resulting filtrate evaporated to dryness under reduced pressure. Trituration under anhydrous diethyl ether gave the title compound as a pale yellow solid (1.5 g, 59%); m/z (API) 257 (M+H+, 100%).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5].[NH4+].[Cl-].C1COCC1.Br[CH2:20][C:21]([CH3:23])=[CH2:22]>CCOC(C)=O.[Zn]>[Cl:1][CH2:2][CH2:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([OH:5])[CH2:22][C:21]([CH3:23])=[CH2:20]
Reactant: C=C(C)CBr
Reactant: O=C(CCCl)c1ccccc1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: C=C(C)CC(O)(CCCl)c1ccccc1
Temperature: 25 °C
Yield: 65.1 %

Procedure:
To a well stirred mixture of 3-chloropropiophenone (10.0 g, 59.3 mmol), zinc powder (4.0 g, 1.03 equiv), satd aq NH4Cl solution (150 mL), THF (70 mL), a solution of the 3-bromo-2-methylprop-1-ene (16 g, 2 equiv) was added slowly. The reaction was exothermic mildly. After the addition, the mixture was heated to reflux for 1.5 h. After being cooled to rt, the mixture was diluted with EtOAc (200 mL), separated, washed with brine (35 mL), and dried over Na2SO4. After filtration and concentration, the residue was purified by chromatography on a 120 g silica gel column, eluted with a 0-10% methanol in CH2Cl2 gradient, to afford 1-chloro-5-methyl-3-phenylhex-5-en-3-ol (8.67 g product, 65% yield).
Reaction SMILES: [C:1]1([C:7]2[N:8]=[C:9]([CH:12]3[CH2:14][CH:13]3[C:15]([O:17][CH2:18][CH3:19])=[O:16])[NH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:20](=O)([O-])[O-].[K+].[K+].IC>CN(C=O)C.CCOCC>[CH3:20][N:10]1[CH:11]=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:8]=[C:9]1[CH:12]1[CH2:14][CH:13]1[C:15]([O:17][CH2:18][CH3:19])=[O:16]
Reactant: O=C([O-])[O-]
Reactant: CCOC(=O)C1CC1c1nc(-c2ccccc2)c[nH]1
Agent: [K+]
Solvent: CI
Solvent: CCOCC
Solvent: CN(C)C=O
Product: CCOC(=O)C1CC1c1nc(-c2ccccc2)cn1C
Temperature: 50 °C
Yield: 65.5 %

Procedure:
To a solution of ethyl 2-(4-phenyl-1H-imidazol-2-yl)cyclopropanecarboxylate (1025 mg, 4 mmol) in DMF (5 mL) was added potassium carbonate (608 mg, 4.40 mmol) followed by iodomethane (0.275 mL, 4.40 mmol) at rt. The reaction mixture was heated at 50° C. for 12 h. Cooled and diluted with ether (30 mL) and washed with water, brine and dried (Na2SO4). TLC (25% EtOAc in hexane) showed presence of starting material (10-20%). Purified by flash chromatography using 25% EtOAc in hexane to give pure ethyl 2-(1-methyl-4-phenyl-1H-imidazol-2-yl)cyclopropanecarboxylate (746 mg, 2.62 mmol, 65.5% yield). The ester solidified to a white solid over a period of time. 1H NMR (500 MHz, CHLOROFORM-d) δ 7.79-7.61 (m, 2H), 7.43-7.27 (m, 2H), 7.24-7.14 (m, 1H), 7.02 (s, 1H), 4.20 (q, J=7.2 Hz, 2H), 3.61 (s, 3H), 2.42 (ddd, J=9.0, 6.2, 4.0 Hz, 1H), 2.29 (ddd, J=8.5, 5.3, 4.1 Hz, 1H), 1.69 (ddd, J=8.5, 6.1, 4.0 Hz, 1H), 1.59 (ddd, J=9.1, 5.3, 3.9 Hz, 1H), 1.30 (t, J=7.1 Hz, 3H); MS (ESI) 271 (M+H); Rf=1.90 (Condition A).
Reaction SMILES: [OH:1][N:2]=[C:3](Cl)[C:4]1[CH:15]=[CH:14][C:7]2[B:8]([OH:13])[O:9][C:10]([CH3:12])([CH3:11])[C:6]=2[CH:5]=1.[Cl:17][C:18]1[CH:23]=[C:22]([C:24]([C:26]([F:29])([F:28])[F:27])=[CH2:25])[C:21]([Cl:30])=[C:20]([Cl:31])[C:19]=1[Cl:32]>CN(C=O)C>[CH3:11][C:10]1([CH3:12])[O:9][B:8]([OH:13])[C:7]2[CH:14]=[CH:15][C:4]([C:3]3[CH2:25][C:24]([C:22]4[CH:23]=[C:18]([Cl:17])[C:19]([Cl:32])=[C:20]([Cl:31])[C:21]=4[Cl:30])([C:26]([F:28])([F:27])[F:29])[O:1][N:2]=3)=[CH:5][C:6]1=2
Reactant: CC1(C)OB(O)c2ccc(C(Cl)=NO)cc21
Reactant: C=C(c1cc(Cl)c(Cl)c(Cl)c1Cl)C(F)(F)F
Solvent: CN(C)C=O
Product: CC1(C)OB(O)c2ccc(C3=NOC(c4cc(Cl)c(Cl)c(Cl)c4Cl)(C(F)(F)F)C3)cc21
Temperature: 25 °C
Reaction time: 12 h
Yield: 19.3 %

Procedure:
To the solution of N,1-dihydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborole-5-carbimidoyl chloride (0.526 mmol) in DMF (3 mL) was added 1,2,3,4-tetrachloro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzene (245 mg, 0.789 mmol) and TEA (106 mg, 1.052 mmol) at rt. The mixture was stirred at 25° C. for 12 h, quenched with water, extracted with EA (3×10 mL). The combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by prep-HPLC to give the final title compound 3,3-dimethyl-5-(5-(2,3,4,5-tetrachlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzo[c][1,2]oxaborol-1(3H)-ol (52 mg; yield 13%) as a solid. 1H NMR (400 MHz, DMSO-d6): δ 9.20 (s, 1H), 7.98 (s, 1H), 7.83 (s, 1H), 7.76-7.47 (d, J=3.2 Hz, 2H), 4.67-4.63 (d, J=18 Hz, 1H), 4.37-4.35 (d, J=18.8 Hz, 1H), 1.49 (s, 3H), 1.48 (s, 3H) ppm; MS: m/z=514 (M+1, ESI+).
Reaction SMILES: CS(O[CH2:6][CH2:7][CH2:8][O:9][C:10]([C:12]1[NH:13][C:14]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:15]2[C:20]=1[CH:19]=[CH:18][C:17]([Cl:21])=[CH:16]2)=[O:11])(=O)=O.[CH2:28]([NH:30][CH2:31][CH3:32])[CH3:29]>CC(C)=O>[ClH:21].[CH2:28]([N:30]([CH2:31][CH3:32])[CH2:6][CH2:7][CH2:8][O:9][C:10]([C:12]1[NH:13][C:14]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:15]2[C:20]=1[CH:19]=[CH:18][C:17]([Cl:21])=[CH:16]2)=[O:11])[CH3:29]
Reactant: CS(=O)(=O)OCCCOC(=O)c1[nH]c(-c2ccccc2)c2cc(Cl)ccc12
Reactant: CCNCC
Solvent: CC(C)=O
Product: CCN(CC)CCCOC(=O)c1[nH]c(-c2ccccc2)c2cc(Cl)ccc12
Product: Cl

Procedure:
A solution of 0.82 g. of 5-chloro-3-phenylisoindole-1-carboxylic acid 3-[(methylsulfonyl)oxy]propyl ester in 8 ml. of acetone is treated with 2 ml. of diethylamine and the mixture is boiled at reflux for 5 hours. The mixture is then concentrated to dryness under reduced pressure and the residue partitioned between 15 ml. of water and 15 ml. of diethyl ether. The ethereal phase is treated with 6 ml. of 0.5-N hydrochloric acid and the mixture shaken well. After cooling in an ice-bath, the hydrochloride which crystallizes out is removed by filtration, dried and recrystallized from methanol/diethyl ether, and there is obtained 5-chloro-3-phenylisoindole-1-carboxylic acid 3-(diethylamino)propyl ester hydrochloride having a melting point of 248°-251° C. (decomposition).
Reaction SMILES: [C:1]([OH:4])(=[O:3])[CH3:2].C(O)(=O)C.O[C@H:10]1[CH2:27][CH2:26][C@@:25]2([CH3:28])[C@@H:12]([CH2:13][CH2:14][C@@H:15]3[C@@H:24]2[CH2:23][CH2:22][C@@:20]2([CH3:21])[C@H:16]3[CH2:17][C@@H:18]([OH:30])[C:19]2=O)[CH2:11]1.[CH3:31][NH2:32]>C(O)C>[C:1]([O:4][C@H:10]1[CH2:27][CH2:26][C@@:25]2([CH3:28])[C@@H:12]([CH2:13][CH2:14][C@@H:15]3[C@@H:24]2[CH2:23][CH2:22][C@@:20]2([CH3:21])[C@H:16]3[CH2:17][C@@H:18]([OH:30])[C@@H:19]2[NH:32][CH3:31])[CH2:11]1)(=[O:3])[CH3:2]
Reactant: CC(=O)O
Reactant: CN
Reactant: C[C@]12CC[C@H](O)C[C@@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)[C@H](O)C[C@@H]12
Solvent: CCO
Product: CN[C@H]1[C@H](O)C[C@H]2[C@@H]3CC[C@H]4C[C@@H](OC(C)=O)CC[C@]4(C)[C@H]3CC[C@@]21C
Reaction time: 0.75 h

Procedure:
3β,16α-Dihydroxy-5α-androstan-17-one diacetate (18.8 g) was dissolved in a solution of methylamine in ethanol (33%; 188 ml) and the solution was stirred for 45 min. during which time a colourless solid precipitated. Sodium borohydride (10 g) was added portionwise to the stirred suspension, while keeping the temperature below 26° C. After 11/2 h. water was added and the product was filtered off and washed with water. The crude material was dissolved in methylene dichloride and the solution was washed with water, dried (MgSO4), evaporated, and the residue (16.2 g) was crystallised from ether to give 17β-methylamino-5α-androstane-3β,16α-diol 3-acetate (12.2 g) as prisms, m.p. 197°-199° C., [α]D -18° (C 1.0).
Reaction SMILES: [OH-].[Na+].[C:3]([O:7][C:8]([N:10]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1)[CH2:11][CH2:12][CH2:13][CH2:14][C:15]([O:17]C)=[O:16])=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl>O.CO>[C:3]([O:7][C:8]([N:10]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1)[CH2:11][CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16])=[O:9])([CH3:6])([CH3:4])[CH3:5]
Reactant: COC(=O)CCCCN(C(=O)OC(C)(C)C)c1ccccn1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CC(C)(C)OC(=O)N(CCCCC(=O)O)c1ccccn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 67.9 %

Procedure:
NaOH (240 mg, 6 mmol) was dissolved in water (3 mL) and MeOH (10 mL). This solution was added to methyl 5-[(tert-butoxycarbonyl)(pyridin-2-yl)amino]pentanoate (200 mg, 0.64 mmol) dissolved in MeOH (15 mL). The mixture was stirred at room temperature overnight. The reaction mixture was neutralized with 2N HCl to pH 7. The solvent was removed under reduced pressure. A citric acid solution (10 mL) was added and the mixture was extracted with ethyl acetate, dried (MgSO4) and concentrated to give 128 mg (68%) of the product. 1H NMR (CDCl3) 8.36-8.34 (m, 1H), 7.65-7.52 (m, 2H), 7.02-6.98 (m, 1H), 3.97-3.91 (m, 2H), 2.38-2.32 (m, 2H), 1.69-1.62 (m, 4H), 1.50 (s, 9H).
Reaction SMILES: [C:1](OC(=O)C)(=O)C.C(O)=O.[NH2:11][N:12]1[C:21]([OH:28])([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([Cl:29])[CH:19]=2)[N:14]=[CH:13]1>C(O)(=O)C>[Cl:29][C:18]1[CH:17]=[CH:16][C:15]([N:14]2[CH:1]=[N:11][N:12]=[CH:13]2)=[C:20]([CH:19]=1)[C:21]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:28]
Reactant: CC(=O)OC(C)=O
Reactant: NN1C=Nc2ccc(Cl)cc2C1(O)c1ccccc1
Solvent: CC(=O)O
Solvent: O=CO
Product: O=C(c1ccccc1)c1cc(Cl)ccc1-n1cnnc1
Reaction time: 18 h

Procedure:
A stirred solution of acetic anhydride (25.3 ml) and 97% formic acid (10.6 ml) is kep at ambient temperature (25°) for 30 minutes, cooled in an ice bath and treated with 3-amino-6-chloro-3,4-dihydro-4-hydroxy-4-phenylquinazoline (12.24 g, 0.0447 mole). The solution is kept at ambient temperature for 18 hours, diluted with acetic acid (25 ml), warmed to the reflux temperature during 1 hour and refluxed for 1.5 hours. The solution is concentrated in vacuo, and the residue is mixed with cold water, made alkaline with sodium hydroxide and extracted with chloroform. The extract is washed with brine, dried over anhydrous sodium sulfate and concentrated. The residue is crystallized from ethylacetate to give 7.76 g of 5-chloro-2-(4H-1,2,4-triazol-4-yl)-benzophenone of melting point 184°-186° C., 0.971 g of melting point 182.5°-184° C., and 0.144 of melting point 181°-182° C.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([NH:8][NH2:9])=[O:7])=[CH:4][CH:3]=1.[CH3:12][C:13]1[S:17][C:16]([CH:18]=O)=[CH:15][CH:14]=1>C(O)(=O)C.CCO>[CH3:18][C:16]1[S:17][C:13]([CH:12]=[N:9][NH:8][C:6](=[O:7])[C:5]2[CH:10]=[CH:11][C:2]([OH:1])=[CH:3][CH:4]=2)=[CH:14][CH:15]=1
Reactant: Cc1ccc(C=O)s1
Reactant: NNC(=O)c1ccc(O)cc1
Solvent: CCO
Solvent: CC(=O)O
Product: Cc1ccc(C=NNC(=O)c2ccc(O)cc2)s1
Temperature: 25 °C
Yield: 57.6 %

Procedure:
To a solution of 4-hydroxy-benzoic acid hydrazide (0.25 g, 0.0016 mol) and 5-methyl-2-thiophenecarboxaldehyde (0.20 g, 0.0016 mol) in abs. EtOH (10 mL), was added 1 drop of acetic acid. The reaction mixture was refluxed for 4 hours. The reaction mixture was cooling to room temperature and concentrated to remove solvent. The resulting residue was solidified by EtOAc to give white solid 0.24 g, in 57% yield, mp: 215.7° C. 1H NMR (CD3OD) δ 8.38 (s, 1H), 7.79 (d, 2H), 7.17 (s, 1H), 6.86 (d, 2H), 6.77 (s, 1H), 2.49 (s, 3H), 1.31. 13C NMR (CDCl3) δ 166.5, 162.8, 145.6, 144.8, 138.1, 132.4, 130.7, 127.1, 124.8, 116.3, 15.6. Anal. Calcd for C13H12N2O2 S: C, 59.98; H, 4.65; N, 10.76. Found: C, 59.98; H, 4.45; N, 10.40.
Reaction SMILES: CC(C)([O-])C.[K+].[C:7]1([CH:13]([SH:15])[CH3:14])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:16](=[S:18])=[S:17].Cl[CH2:20][C:21]#[N:22]>O1CCCC1>[C:16](=[S:18])([S:15][CH:13]([CH3:14])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[S:17][CH2:20][C:21]#[N:22]
Reactant: N#CCCl
Reactant: S=C=S
Reactant: CC(S)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC(SC(=S)SCC#N)c1ccccc1
Temperature: 18 °C
Reaction time: 0.5 h
Yield: 88.8 %

Procedure:
To a solution of 5.6 g (50 mmol) of potassium t-butoxide in 100 ml of tetrahydrofuran is added 8.7 ml (8.94 g, 60 mmol) of 92% 1-phenylethylmercaptan while maintaining the temperature of the reaction mixture between 20° and 25° C. The resulting suspension is cooled to 18° C. and 4.35 ml (72 mmol) of carbon disulfide is added thereto. The yellow solution which forms is stirred for 0.5 hours and then 3.23 ml (50 mmol) of chloroacetonitrile is added while the temperature of the reaction mixture is maintained at about 20° C. After stirring for 0.5 hour, the mixture is concentrated in vacuo. The residue is taken up in ether and the ether solution washed with water, brine, dried with Na2SO4 and concentrated in vacuo. The residue is chromatographed on a silica gel dry-column and eluted with 1:2 CH2Cl2 -hexane. The yellow band is collected to give 11.25 g (89%) of a yellow oil, cyanomethyl α-methylbenzyl trithiocarbonate.
Reaction SMILES: [C:1]([O-:10])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].[Na+].[CH:12]1[C:17](=[O:18])[C:16]([OH:19])=[CH:15][O:14][C:13]=1[CH2:20]Cl.CN(C)C=O>C(OCC)(=O)C>[OH:4][C:3]1[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=1[C:1]([O:10][CH2:20][C:13]1[O:14][CH:15]=[C:16]([OH:19])[C:17](=[O:18])[CH:12]=1)=[O:9]
Reactant: O=C([O-])c1ccccc1O
Reactant: O=c1cc(CCl)occ1O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=C(OCc1cc(=O)c(O)co1)c1ccccc1O
Temperature: 110 °C
Reaction time: 2 h
Yield: 52.3 %

Procedure:
1 g(6.2 mmole) of sodium salicylate and 0.9 g(15.6 mmole) of chlorokojic acid were dissolved into 70 ml of N,N-dimethylformamide. The resulting solution was heated with stirring for 2 hours in an oil bath of 110° C. After distillating solvent, the residue was dissolved in 300 ml of ethyl acetate. The ethyl acetate solution was washed with 5% chloric acid and distilled water, dried over magnesium sulfate, decolored with active charcoal and filtered. The filtrate was concentrated to give 0.85 g(58%) of 2-(2-hydroxybenzoyl) oxymethyl-5-hydroxy-4H-pyran-4-one as a solid.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[N:5]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C:4](=[O:21])[C:3]=1[C:22]#[N:23].[NH:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1>ClCCl>[F:20][C:17]1[CH:18]=[CH:19][C:14]([CH2:13][N:5]2[C:6]3[C:11](=[CH:10][C:9]([CH3:12])=[CH:8][CH:7]=3)[C:2]([N:24]3[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]3)=[C:3]([C:22]#[N:23])[C:4]2=[O:21])=[CH:15][CH:16]=1
Reactant: C1CNCCN1
Reactant: Cc1ccc2c(c1)c(Cl)c(C#N)c(=O)n2Cc1ccc(F)cc1
Solvent: ClCCl
Product: Cc1ccc2c(c1)c(N1CCNCC1)c(C#N)c(=O)n2Cc1ccc(F)cc1
Yield: 70.5 %

Procedure:
A solution of Compound 22 (1.6 g, 4.9 mmol) in dichloromethane was added slowly to a stirred solution of piperazine (2.2 g, 24.5 mmol) in CH2Cl2 at room temperature and further stirred overnight. The solvent was removed under reduced pressure. The residue was taken in water, sonicated briefly, and filtered. The solids were dissolved in ethyl acetate and washed by water. The organic layer was dried over Na2SO4 and concentrated to yield 1.30 g (72%) of yellow solids. M.P. 121° C. 1H NMR (DMSO-d6): δ 2.35 (s, 3H), 2.96 (m, 4H), 3.54 (m, 4H), 5.42 (s, 2H), 7.11–7.17 (m, 2H), 7.23–7.26 (m, 2H), 7.44 (dd, J=1.2, 8.6 Hz, 1H), 7.64 (s, 1H). EIMS m/z 377 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][CH2:13][C@H:14]([NH2:16])[CH3:15])=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.[CH3:17][N:18]([CH3:27])[C:19]1[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][CH:20]=1.[BH4-].[Na+].C(O)(=O)C>C(O)C>[ClH:1].[ClH:1].[ClH:1].[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][CH2:13][C@H:14]([NH:16][CH2:23][C:22]3[CH:25]=[CH:26][C:19]([N:18]([CH3:27])[CH3:17])=[CH:20][CH:21]=3)[CH3:15])=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1
Reactant: CN(C)c1ccc(C=O)cc1
Reactant: C[C@@H](N)CNc1ccnc2cc(Cl)ccc12
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: CC(=O)O
Product: C[C@H](CNc1ccnc2cc(Cl)ccc12)NCc1ccc(N(C)C)cc1
Product: Cl

Procedure:
0.35 g of (2R)-N1 -(7-chloro-quinolin-4-yl)-propane-1,2-diamine (see Example 118) and 0.22g of 4-dimethylamino-benzaldehyde were boiled under reflux in 50 ml of ethanol overnight. After evaporation of the solvent the residue was again taken up in 20 ml of ethanol, 0.05 g of sodium borohydride was added thereto and the mixture was left to react at room temperature overnight. The excess sodium borohydride was then decomposed by the addition of 5 ml of glacial acetic acid and the solvent was evaporated. After the addition of 10 ml of methanol the mixture was again evaporated. Addition of methanol and evaporation were repeated again, whereafter the mixture was purified by chromatography on 30 g of silica gel with a mixture of dichloromethane and methanol in the ratio by volume 10:1. The product-containing fractions were combined and evaporated, and the residue was taken up in 5 ml of ethanol. After the addition of 5 ml of 3N isopropanolic hydrochloric acid the hydrochloride of the product precipitated and was recrystallized from ethanol/diethyl ether.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:16][OH:17].C([O-])(=O)C.[Na+]>C(O)C>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=[N:16][OH:17])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NO
Reactant: O=C1CCN(Cc2ccccc2)CC1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: ON=C1CCN(Cc2ccccc2)CC1

Procedure:
18.9 g of 1-benzyl-4-oxopiperidine, 26.8 g of hydroxylamine hydrochloride, and 24.8 g of sodium acetate in 200 ml of ethanol are stirred for 8 hours.