Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[C:2]1[CH:3]=[C:4]([CH3:9])[CH:5]=[C:6]([CH3:8])[CH:7]=1.[SH:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1.C([O-])([O-])=O.[K+].[K+].C(O)CO>[Cu]I.CC(O)C>[CH3:8][C:6]1[CH:7]=[C:2]([S:10][C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)[CH:3]=[C:4]([CH3:9])[CH:5]=1
Reactant: Cc1cc(C)cc(I)c1
Reactant: Oc1ccc(S)cc1
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)O
Solvent: OCCO
Product: Cc1cc(C)cc(Sc2ccc(O)cc2)c1
Yield: 89.9 %

Procedure:
The general procedure in example 39 was followed. 5-Iodo-m-xylene (144 μL, 1.0 mmol), 4-mercaptophenol (126 mg, 1.0 mmol), CuI (10 mg, 0.05 mmol), K2CO3 (276 mg, 2.0 mmol), ethylene glycol (111 μL, 2.0 mmol) and 2-propanol (1.0 mL) were used to obtain the 4-(3,5-dimethylphenyl)sulfanylphenol (207 mg, 90% yield) as colorless liquid. Workup procedure: ethyl acetate (approx. 5 mL) and dodecane (227 μL, GC standard) were added to the reaction mixture after the reaction was completed. The organic layer was neutralized by dilute HCl to pH 8. The aqueous layer was extracted by ethyl acetate (4×10 mL). The combined organic layers were concentrated and purified by column chromatography on silica gel using hexane/ethyl acetate=10/1 as the eluent to afford the titled product. Rf=0.3 (hexane/ethyl acetate=10/1). 1H NMR (CDCl3, 300 MHz) δ 7.33 (dt, 2 H, J=1.8 Hz, 8.4 Hz), 6.77-6.81 (m, 5 H), 4.83 (s, 1 H), 2.22 (s, 6 H). 13C NMR (CDCl3, 75 MHz) δ 155.6, 138.8, 137.7, 135.4, 128.1, 126.4, 125.3, 116.6, 21.6. IR (neat, cm−1) 3371 (broad), 3031, 2917, 2860. MS (EI) m/z (relative intensity) 230 (100), 215 (20). Anal Cald for C14H14OS, Cald. C, 73.01; H, 6.13. Found C, 73.21; H, 6.11.
Reaction SMILES: [OH-].[Li+].[N:3]1[CH:8]=[CH:7][CH:6]=[C:5]([C:9]2([C:12]([O:14]CC)=[O:13])[CH2:11][CH2:10]2)[N:4]=1>O1CCCC1.O>[N:3]1[CH:8]=[CH:7][CH:6]=[C:5]([C:9]2([C:12]([OH:14])=[O:13])[CH2:10][CH2:11]2)[N:4]=1
Reactant: CCOC(=O)C1(c2cccnn2)CC1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)C1(c2cccnn2)CC1
Reaction time: 2 h
Yield: 0.6 %

Procedure:
Lithium hydroxide (196.4 mg, 4.68 mmol) was added to a solution of ethyl 1-(pyridazin-3-yl)cyclopropanecarboxylate (300 mg, 156 mmol) in tetrahydrofuran and water (1:1, 10 mL) at room temperature. The reaction mixture was stirred for 2 h and concentrated. The resulting residue was dissolved in water and the pH was adjusted to 2 using 1N aqueous hydrochloric acid. The mixture was extracted with ethyl acetate. The organics were dried over sodium sulfate and concentrated to afford the title compound (160 mg) which was used as is without further purification. MS (ES+APCI) (M−H) 163.0; LCMS retention time: 2.713 minutes (Method X1)
Reaction SMILES: [I:1][C:2]1[C:6]2[CH:7]=[N:8][CH:9]=[CH:10][C:5]=2[N:4]([CH:11]([CH3:14])[CH2:12][OH:13])[CH:3]=1.N1C=CN=C1.[CH3:20][C:21]([Si:24](Cl)([CH3:26])[CH3:25])([CH3:23])[CH3:22].O>C(Cl)Cl>[Si:24]([O:13][CH2:12][CH:11]([N:4]1[C:5]2[CH:10]=[CH:9][N:8]=[CH:7][C:6]=2[C:2]([I:1])=[CH:3]1)[CH3:14])([C:21]([CH3:23])([CH3:22])[CH3:20])([CH3:26])[CH3:25]
Reactant: CC(CO)n1cc(I)c2cnccc21
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: ClCCl
Solvent: O
Product: CC(CO[Si](C)(C)C(C)(C)C)n1cc(I)c2cnccc21
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 94.6 %

Procedure:
To a solution of 2-(3-iodo-1H-pyrrolo[3,2-c]pyridin-1-yl)propan-1-ol (Preparation 56, 11.5 g, 38.1 mmol) and imidazole (6.48 g, 95.2 mmol) in DCM (300 mL) was added a solution of TBDMSCl (6.95 g, 45.7 mmol) in DCM (50 mL) dropwise at 0° C. The reaction was allowed to warm to room temperature and stirred for 1.5 hours. To the reaction was added water (500 mL) and DCM (200 mL), the organic layer collected, dried over MgSO4 and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 0-10% MeOH in DCM to afford the title compound (15 g, 100%).
Reaction SMILES: CS[C:3](SC)=[C:4]1[C:13](=[O:14])[C:12]([CH3:20])([CH2:15][CH2:16][CH:17]([CH3:19])[CH3:18])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]1=[O:21].[NH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[S:31]([NH2:34])(=[O:33])=[O:32]>C1(C)C=CC=CC=1>[O:32]=[S:31]1(=[O:33])[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[NH:24][C:3]([C:4]2[C:13](=[O:14])[C:12]([CH3:20])([CH2:15][CH2:16][CH:17]([CH3:18])[CH3:19])[C:11]3[C:6]([C:5]=2[OH:21])=[CH:7][CH:8]=[CH:9][CH:10]=3)=[N:34]1
Reactant: Nc1ccccc1S(N)(=O)=O
Reactant: CSC(SC)=C1C(=O)c2ccccc2C(C)(CCC(C)C)C1=O
Solvent: Cc1ccccc1
Product: CC(C)CCC1(C)C(=O)C(C2=NS(=O)(=O)c3ccccc3N2)=C(O)c2ccccc21
Temperature: 25 °C
Yield: 98.9 %

Procedure:
A solution of Example 28F (0.087 g, 0.250 mmol) and 2-amino-benzenesulfonamide (0.045 g, 0.262 mmol) in toluene (7 mL) was refluxed for 6 hours. The solution was cooled to 25° C. and concentrated in vacuo. The residue was chromatographed on silica gel eluting with hexane followed by 20% and 30% ethyl acetate in hexane to give the desired product (0.105 g, 99%).
Reaction SMILES: C1C=C[NH+]=CC=1.[Br:7][Br-]Br.[O:10]1[CH2:14][CH2:13][C:12]2[CH:15]=[C:16]3[C:21](=[CH:22][C:11]1=2)[CH2:20][CH2:19][CH2:18][C:17]3=[O:23]>C(Cl)(Cl)Cl>[Br:7][CH:18]1[CH2:19][CH2:20][C:21]2[C:16](=[CH:15][C:12]3[CH2:13][CH2:14][O:10][C:11]=3[CH:22]=2)[C:17]1=[O:23]
Reactant: O=C1CCCc2cc3c(cc21)CCO3
Agent: c1cc[nH+]cc1
Solvent: ClC(Cl)Cl
Product: O=C1c2cc3c(cc2CCC1Br)OCC3
Reaction time: 8 h
Yield: 103.6 %

Procedure:
55.33 g of pyridinium bromide perbromide are added portionwise at 0° C. to a solution of 27.1 g of 2,3,5,6,7,8-hexahydronaphtho[2,3-b]furan-5-one, the compound of Example 17, in 1.5 of chloroform. The mixture is left overnight at room temperature. The reaction mixture is then washed with water and the organic phase dried over anhydrous magnesium sulfate. Evaporation of the chloroform yields 39.85 g of a mixture which is then purified on a silica column using a mixture of methylene chloride and cyclohexane (80:20 V/V) as solvent. The product obtained is then recrystallized in ethyl acetate.
Reaction SMILES: C(OC(OCC)[N:5]1[CH:9]=[CH:8][N:7]=[CH:6]1)C.C([Li])CCC.[CH3:18][C:19]1[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][C:20]=1[CH:21]=[O:22]>O1CCCC1>[CH3:18][C:19]1[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][C:20]=1[CH:21]([C:6]1[NH:5][CH:9]=[CH:8][N:7]=1)[OH:22]
Reactant: CCOC(OCC)n1ccnc1
Reactant: Cc1cccc(C=O)c1C
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: Cc1cccc(C(O)c2ncc[nH]2)c1C
Temperature: -78 °C
Reaction time: 2 h
Yield: 72 %

Procedure:
To a solution of 1-(diethoxymethyl)-1H-imidazole (698 mg, 4.10 mmol) in anhydrous tetrahydrofuran (7 ml), at −78° C., was added n-butyllithium (2.5 M in hexane, 1.64 ml, 4.1 mmol). The reaction mixture was stirred at −78° C. for 1 h, before addition of a solution of 2,3-dimethylbenzaldehyde (500 mg, 3.73 mmol) in tetrahydrofuran (3 ml). The reaction mixture was stirred at −78° C. for 2 h, warmed to room temperature and quenched with ice cold hydrochloric acid (4M, 20 ml). The reaction mixture was concentrated in vacuo and to the residue was added water (20 ml). The solution was extracted with diethyl ether (2×20 ml) and the aqueous layer was basified by addition of solid sodium hydrogen carbonate. This solution was extracted with ethyl acetate (3×20 ml) and the combined organic phases were dried (MgSO4) and concentrated in vacuo to give the title compound (543 mg)
Reaction SMILES: [Br:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8](I)[N:7]=3.C([Sn](CCCC)(CCCC)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1)CCC>CN(C=O)C.[Cu](I)I>[Br:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1)[N:7]=3
Reactant: Brc1ccc2c(c1)OCCn1cc(I)nc1-2
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccccn1
Agent: I[Cu]I
Solvent: CN(C)C=O
Product: Brc1ccc2c(c1)OCCn1cc(-c3ccccn3)nc1-2
Temperature: 100 °C
Yield: 73.2 %

Procedure:
A mixture of 8-bromo-2-iodo-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (300 mg, 0.767 mmol), 2-tributylstannanylpyridine (339 mg, 0.921 mmol), Pd2(PPh3)2Cl2 (54 mg, 0.077 mmol) and copper iodide (44 mg, 0.23 mmol) in DMF (6 mL) was purged with nitrogen and then heated at 100° C. for 1 h using microwave irradiation. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The product containing fractions were concentrated in vacuo and the resulting residue was purified by column chromatography (Si-PCC, gradient 0-10% MeOH in DCM followed by Si-PCC, gradient 0-2% 2M NH3/MeOH in DCM) affording the title compound as a white solid (192 mg, 73%). LCMS: RT 3.37 min [M+H]+ 341.9/343.9
Reaction SMILES: C(OC([N:8]1[CH2:17][CH2:16][C:15]2[C:11](=[C:12](OS(C(F)(F)F)(=O)=O)[N:13]([CH:18]([CH3:20])[CH3:19])[N:14]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[CH3:29][C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1>>[CH:18]([N:13]1[C:12]([C:33]2[CH:34]=[CH:35][C:30]([CH3:29])=[CH:31][CH:32]=2)=[C:11]2[C:15]([CH2:16][CH2:17][NH:8][CH2:9][CH2:10]2)=[N:14]1)([CH3:19])[CH3:20]
Reactant: CC(C)n1nc2c(c1OS(=O)(=O)C(F)(F)F)CCN(C(=O)OC(C)(C)C)CC2
Reactant: Cc1ccc(B(O)O)cc1
Product: Cc1ccc(-c2c3c(nn2C(C)C)CCNCC3)cc1
Yield: 100.3 %

Procedure:
The title compound (129 mg) was prepared as in Example 177, Steps C and D, using 204 mg of 2-isopropyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step A) and 194 mg of 4-methylphenylboronic acid. MS (ESI): exact mass calculated for C17H23N3, 269.19. found, m/z 270.5 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.28 (d, J=7.7 Hz, 2H), 7.12 (d, J=7.7 Hz, 2H), 4.32 (m, 1H), 3.34-3.33 (m, 2H), 3.12-3.10 (m, 2H), 2.70-2.68 (m, 2H), 2.33 (s, 3H), 1.30 (d, J=6.6 Hz, 6H).
Reaction SMILES: [OH-].[Li+].O.C([O:6][P:7]([CH2:16][C@@H:17]([OH:29])[CH2:18][NH:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([Cl:28])[CH:22]=1)([CH:9]([O:13][CH2:14][CH3:15])[O:10][CH2:11][CH3:12])=[O:8])C>C(O)C>[Cl:28][C:23]1[CH:22]=[C:21]([CH:26]=[CH:25][C:24]=1[Cl:27])[CH2:20][NH:19][CH2:18][C@H:17]([OH:29])[CH2:16][P:7]([CH:9]([O:10][CH2:11][CH3:12])[O:13][CH2:14][CH3:15])(=[O:6])[OH:8]
Reactant: CCOC(OCC)P(=O)(C[C@@H](O)CNCc1ccc(Cl)c(Cl)c1)OCC
Agent: [Li+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CCOC(OCC)P(=O)(O)C[C@@H](O)CNCc1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
0.254 g of lithium hydroxide and 6 ml of water are added to a solution of 2.26 g of 3-[N-(3,4-dichlorobenzyl)amino]-2(S)-hydroxy-propyl(diethoxymethyl)-phosphinic acid ethyl ester in 3 ml of ethanol and the mixture is stirred at 60° for 24 hours. The mixture is allowed to cool to room temperature, adjusted to pH 7 with aqueous phsophoric acid and concentrated to dryness by evaporation. The evaporation residue is made into a slurry in hot methanol and filtered. The filtrate is concentrated to dryness by evaporation and the glassy evaporation residue is taken up in a small amount of ethanol. The pH value is adjusted to pH 1 with ethanolic hydrochloric acid and the solvent is removed. Crystallisation from acetonitrile yields 3-[N-(3,4-dichlorobenzyl)amino]-2(S)-hydroxy-propyl(diethoxymethyl)phosphinic acid; [α]20D =-10.8°±1.7° (c=0.595 in methanol); 1H-NMR (CD3OD): δ=7.76 (1H,m), 7.61 (1H,m), 7.45 (1H,m), 4.46 (1H,d), 4.29 (1H,m), 4.20 (2H,m) 3.80 (2H,m), 3.69 (2H,m), 3.25 (1H,dd), 3.02 (1H,d,d), 2.04 (1H,dd), 1.87 (1H,d,d); 1.20 (6H,t).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:13][NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:6]=[CH:7][C:8]=1[C:9]([O:11][CH3:12])=[O:10].[Cl:22][C:23]1[CH:33]=[CH:32][C:31]([S:34](=[O:40])(=[O:39])[NH:35][CH:36]2[CH2:38][CH2:37]2)=[CH:30][C:24]=1[C:25]([N:27]=[C:28]=[O:29])=[O:26]>C(Cl)Cl>[Cl:22][C:23]1[CH:33]=[CH:32][C:31]([S:34](=[O:40])(=[O:39])[NH:35][CH:36]2[CH2:38][CH2:37]2)=[CH:30][C:24]=1[C:25]([NH:27][C:28]([N:13]([C:5]1[CH:6]=[CH:7][C:8]([C:9]([O:11][CH3:12])=[O:10])=[C:3]([O:2][CH3:1])[CH:4]=1)[NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[O:29])=[O:26]
Reactant: COC(=O)c1ccc(NNC(=O)OC(C)(C)C)cc1OC
Reactant: O=C=NC(=O)c1cc(S(=O)(=O)NC2CC2)ccc1Cl
Solvent: ClCCl
Product: COC(=O)c1ccc(N(NC(=O)OC(C)(C)C)C(=O)NC(=O)c2cc(S(=O)(=O)NC3CC3)ccc2Cl)cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 16.5 %

Procedure:
To a solution of tert-butyl 2-(3-methoxy-4-(methoxycarbonyl)phenyl)hydrazinecarboxylate (Intermediate 14, 1.5 g, 5.08 mmol) in DCM (20 mL) was added 2-chloro-5-(N-cyclopropylsulfamoyl)benzoyl isocyanate (1.6 g, 5.32 mmol). The reaction mass was stirred at RT for 2 h. Excess of solvent was removed under vacuum to afford 0.500 g of desired product. 1H NMR (300 MHz, DMSO d6): δ 0.50 (m, 4H), 1.41 (s, 9H), 2.11 (m, 1H), 3.68-3.75 (m, 6H), 7.59 (d, J=8.7 Hz, 1H), 7.78-7.87 (m, 4H), 8.10 (m, 2H), 8.27 (s, 1H), 8.95 (s, 1H).
Reaction SMILES: [CH:1]1[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[O:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[N+:14]([O-])([OH:16])=[O:15]>C(O)(=O)C>[N+:14]([C:3]1[CH:2]=[CH:1][C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[O:6][C:5]=2[CH:4]=1)([O-:16])=[O:15]
Reactant: c1ccc2c(c1)oc1ccccc12
Reactant: O=[N+]([O-])O
Solvent: CC(=O)O
Product: O=[N+]([O-])c1ccc2c(c1)oc1ccccc12
Temperature: 65 °C
Reaction time: 3 h

Procedure:
Combine dibenzofurane (20.0 g, 0.11 mol) and acetic acid (80 ml). Heat to 65° C. Add 98% nitric acid (20.0 g, 11.8 mol). After 3 hours, cool to room temperature to give a solid. Collect the solid by filtration, rinse with water, and dry to give the title compound.
Reaction SMILES: Cl.[F:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[NH:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH2:6][NH2:7].[C:16]([C:20]1[N:25]=[CH:24][C:23]([CH:26]=[CH:27][C:28](O)=[O:29])=[C:22]([C:31]([F:34])([F:33])[F:32])[CH:21]=1)([CH3:19])([CH3:18])[CH3:17].CN1C(=O)CCC1>C1COCC1>[C:16]([C:20]1[N:25]=[CH:24][C:23]([CH:26]=[CH:27][C:28]([NH:7][CH2:6][C:5]2[CH:8]=[CH:9][C:10]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])=[C:3]([F:2])[CH:4]=2)=[O:29])=[C:22]([C:31]([F:34])([F:32])[F:33])[CH:21]=1)([CH3:19])([CH3:17])[CH3:18]
Reactant: CS(=O)(=O)Nc1ccc(CN)cc1F
Reactant: CC(C)(C)c1cc(C(F)(F)F)c(C=CC(=O)O)cn1
Agent: Cl
Solvent: C1CCOC1
Solvent: CN1CCCC1=O
Product: CC(C)(C)c1cc(C(F)(F)F)c(C=CC(=O)NCc2ccc(NS(C)(=O)=O)c(F)c2)cn1
Yield: 62.7 %

Procedure:
3-Fluoro-4-methanesulfonylaminobenzylamine hydrochloride (41.2 mg, 0.162 mmol) was reacted with 3-(6-tert-butyl-4-trifluoromethyl-pyridin-3-yl)-acrylic acid (1.0 eq, 44.2 mg) DMTMM (1.0 eq, 44.8 mg) and NMP (1.2 eq, 22 μl) in THF to give the title compound (48 mg, 62.6%) after purification by column chromatography (Hex/EtOAc=1/1).
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[NH:13][C:14]([S:20][C:21]2[CH:26]=[C:25]([Cl:27])[CH:24]=[C:23]([Cl:28])[CH:22]=2)=[C:15]([CH:17]([CH3:19])[CH3:18])[N:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Li+].[Li+].S(OCC)(O[CH2:39][CH3:40])(=O)=O>C(#N)C.O>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[N:13]([CH2:39][CH3:40])[C:14]([S:20][C:21]2[CH:26]=[C:25]([Cl:27])[CH:24]=[C:23]([Cl:28])[CH:22]=2)=[C:15]([CH:17]([CH3:19])[CH3:18])[N:16]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOS(=O)(=O)OCC
Reactant: CC(C)c1nc(CCCOCc2ccccc2)[nH]c1Sc1cc(Cl)cc(Cl)c1
Agent: O=C([O-])[O-]
Agent: [Li+]
Solvent: CC#N
Solvent: O
Product: CCn1c(CCCOCc2ccccc2)nc(C(C)C)c1Sc1cc(Cl)cc(Cl)c1
Temperature: 70 °C
Yield: 99.4 %

Procedure:
In 25 ml of dry acetonitrile was dissolved 5.0 g (11.5 mmol) of imidazole (101e), followed by addition of 1.7 g (23 mmol) of lithium carbonate and 2.7 g (17.5 mmol) of diethyl sulfate. The mixture was stirred under heating at 70° C. for 23 hours. After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate. The extract was washed with water, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate) to provide 5.3 g (yield 98%) of 2-(3-benzyloxypropyl)-5-(3,5-dichlorophenylthio)-4-isopropyl-1-ethyl-1H-imidazole (136b) as oil.
Reaction SMILES: [CH3:1][C:2]1[C:8](=[O:9])[C:7]2[N:10]3[C@@:14]([O:21][CH3:22])([C@H:15]([CH2:16][O:17][C:18]([NH2:20])=[O:19])[C:6]=2[C:4](=[O:5])[C:3]=1OC)[C@H:13]1[NH:23][C@H:12]1[CH2:11]3.[CH:26]1[C:31]([NH2:32])=[CH:30][CH:29]=[C:28]([OH:33])[CH:27]=1>CO>[CH3:1][C:2]1[C:8](=[O:9])[C:7]2[N:10]3[C@@:14]([O:21][CH3:22])([C@H:15]([CH2:16][O:17][C:18]([NH2:20])=[O:19])[C:6]=2[C:4](=[O:5])[C:3]=1[NH:32][C:31]1[CH:26]=[CH:27][C:28]([OH:33])=[CH:29][CH:30]=1)[CH:13]1[NH:23][CH:12]1[CH2:11]3
Reactant: COC1=C(C)C(=O)C2=C(C1=O)[C@@H](COC(N)=O)[C@@]1(OC)[C@H]3N[C@H]3CN21
Reactant: Nc1ccc(O)cc1
Solvent: CO
Product: CO[C@]12C3NC3CN1C1=C(C(=O)C(Nc3ccc(O)cc3)=C(C)C1=O)[C@H]2COC(N)=O
Temperature: 25 °C
Reaction time: 5 h
Yield: 77.8 %

Procedure:
Mitomycin A (1 g) and p-aminophenol (2 g) are added to methanol (100 ml) and the mixture is stirred for 5 hours at room temperature. After completion of the reaction, the reaction solution is concentrated under reduced pressure and then dried in vacuo. The dried product is then subjected to silica gel column chromatography developed by acetone-chloroform mixture (1:1) and recrystallized from an acetone-ether mixture to obtain a desired product (950 mg) in the form of green needle crystals with a yield of 78%. This product shows a green spot (Rf=0.1) by silica gel thin layer chromatography using acetone-chloroform mixture (1:1) as developer. The product does not show a precise melting point.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([OH:17])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:18][O:19][C:20]1[CH:21]=[C:22]([CH2:28][CH2:29][NH2:30])[CH:23]=[CH:24][C:25]=1[O:26][CH3:27].O>ClCCl>[CH3:18][O:19][C:20]1[CH:21]=[C:22]([CH2:28][CH2:29][NH:30][C:15](=[O:17])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:23]=[CH:24][C:25]=1[O:26][CH3:27]
Reactant: O=C(O)CCCCCCCCc1ccccc1
Reactant: COc1ccc(CCN)cc1OC
Solvent: O
Solvent: ClCCl
Product: COc1ccc(CCNC(=O)CCCCCCCCc2ccccc2)cc1OC
Reaction time: 18 h

Procedure:
A solution of 9-phenylnonanoic acid (1.934 g) and N,N'-carbonyldiimidazole (1.34 g) in dry dichloromethane (20 ml) was stirred at 20° for one hour and a solution of 3,4-dimethoxybenzeneethanamine (1.4 ml) in dry dichloromethane (10 ml) then added. The mixture was stirred at 20° for 18 hours and water added. The organic phase was separated, washed with dilute hydrochloric acid, aqueous sodium bicarbonate and brine, dried over magnesium sulphate and evaporated to leave a solid. Crystallisation from 2-propanol gave the amide as colourless prisms (2.7 g); mp, 117°-119°.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2].CO[CH:12](OC)[N:13]([CH3:15])[CH3:14].C(OCC)C>CCCCCC>[CH3:12][N:13]([CH3:15])[CH:14]=[CH:2][C:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1)=[O:3]
Reactant: COC(OC)N(C)C
Reactant: CC(=O)c1cccnc1
Solvent: CCCCCC
Solvent: CCOCC
Product: CN(C)C=CC(=O)c1cccnc1
Temperature: 0 °C
Reaction time: 4 h
Yield: 358.4 %

Procedure:
3-Acetylpyridine (100 g, 0.19 mol) was added to dimethylformamide dimethylacetal (156.5 g, 1.27 mol), and the mixture was reacted under reflux for 23 hours. After the reaction mixture was cooled to 0° C., a mixture of diethyl ether and hexane (3:2, v/v) (500 ml) was added and the whole mixture was stirred for 4 hours. The resulting solid was filtered and washed with a mixture of diethyl ether and hexane (500 ml, 3/2, v/v) to give 3-dimethylamino-1-(3-pyridyl)-2-propen-1-one (120 g).
Reaction SMILES: OS(O)(=O)=O.[Br:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=[O:12])=[CH:9][C:8]=1[SH:16].[CH3:17]O>>[CH3:17][O:12][C:11](=[O:13])[C:10]1[CH:14]=[CH:15][C:7]([Br:6])=[C:8]([SH:16])[CH:9]=1
Reactant: O=C(O)c1ccc(Br)c(S)c1
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)c1ccc(Br)c(S)c1

Procedure:
Conc. H2SO4 (6.25 mL) was added dropwise to a refluxing solution of Example 1b and its dimer (3 g) in dry MeOH (60 mL). The reaction mixture was refluxed for 15 h, concentrated and treated with ice to obtain a mixture of the desired ester and that of its dimer, which was filtered, washed with water and dried. Purification was effected using flash chromatography (silica gel, EtOAc/PE60-80° C.) to obtain the title compound and its dimer ester (2.8 g) which was in turn converted into the title compound as given below: Triphenylphosphine (1.5 g, 5.71 mmol) was added to a solution of the dimer ester in MeOH/H2O (15 mL 4:1, v/v) and allowed to stir overnight at room temperature. The reaction mixture was concentrated, treated with water and extracted with ethyl acetate. The ethyl acetate layer was concentrated and the crude obtained was purified using flash chromatography as above to obtain more of the title compound. Yield: 2.0 g, (72%); mp: 81° C.; 1H NMR (CDCl3): δ 3.90 (s, 3H, OCH3), 4.0 (s, 1H, SH), 7.05-7.25 (m, 3H, Ar); MS: m/e (EI+) 247 (M+).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:31]=[CH:32][CH:33]=1)[CH2:6][N:7]1[CH2:11][CH2:10][C@H:9]([NH:12][S:13]([C:16]2[S:17][C:18]([C:21]3[CH:26]=[CH:25][N:24]=[C:23](S(C)=O)[N:22]=3)=[CH:19][CH:20]=2)(=[O:15])=[O:14])[C:8]1=[O:30])#[N:2].C(C1C=C(C=CC=1)CN1CC[C@H](NS(C2SC(C3C=CN=C(S(C)(=O)=O)N=3)=CC=2)(=O)=O)[C:41]1=[O:64])#N>CO>[C:1]([C:3]1[CH:4]=[C:5]([CH:31]=[CH:32][CH:33]=1)[CH2:6][N:7]1[CH2:11][CH2:10][C@H:9]([NH:12][S:13]([C:16]2[S:17][C:18]([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([O:64][CH3:41])[N:22]=3)=[CH:19][CH:20]=2)(=[O:15])=[O:14])[C:8]1=[O:30])#[N:2]
Reactant: CS(=O)(=O)c1nccc(-c2ccc(S(=O)(=O)N[C@H]3CCN(Cc4cccc(C#N)c4)C3=O)s2)n1
Reactant: CS(=O)c1nccc(-c2ccc(S(=O)(=O)N[C@H]3CCN(Cc4cccc(C#N)c4)C3=O)s2)n1
Solvent: CO
Product: COc1nccc(-c2ccc(S(=O)(=O)N[C@H]3CCN(Cc4cccc(C#N)c4)C3=O)s2)n1

Procedure:
A mixture of [5-(2-methylsulfinyl-pyrimidin-4-yl)-thiophene-2-sulfonic acid [1-(3-cyanobenzyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide and [5-(2-methylsulfonyl-pyrimidin-4-yl)-thiophene-2-sulfonic acid [1-(3-cyanobenzyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide (0.19 g, 0.37 mmol) is dissolved in 10 mL of MeOH and 1 mL of CH2Cl2 and NH3 gas is bubbled through the solution for 5 minutes. The resulting mixture is heated at reflux for 4 hours. After this time, the solution is concentrated in vacuo to give the title compound (0.17 g, 0.36 mmol) as a solid.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][O:8][C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]=1[CH:19]([S:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:20][N+:21]([O-])=O.CCOCC>CCOCC.C1COCC1>[CH3:7][O:8][C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]=1[CH:19]([S:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:20][NH2:21]
Reactant: COc1ccc2ccccc2c1C(C[N+](=O)[O-])Sc1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: COc1ccc2ccccc2c1C(CN)Sc1ccccc1
Temperature: 0 °C
Yield: 70 %

Procedure:
To a vigorously stirred suspension of lithium aluminum hydride (76 mg. 20 mmol) in anhydrous ether - THF 2:1 solvent mixture (80 ml) a solution of 1-(2-methoxynaphth-1-yl)-1-(phenylthio)-2-nitroethane (3394 mg, 10 mmol) in ether- THF 2:1 (40 ml) is added dropwise. The reaction mixture is heated at reflux for 24 h and then cooled to 0° C. Ether is added and the excess of LiAlH4 is destroyed by the cautious successive addition of water (2 ml) and 2N NaOH solution (4 ml). The aluminum salts are filtered off and the organic layer evaporated in vacuo. The residue is dissolved in ether and the ethereal solution extracted with 2N HCl solution. The aqueous acidic layer is brought to pH 9 by addition of 2N NaOH and extracted with ether. The ethereal layer is dried with Na2SO4 and then evaporated to dryness in vacuo to give almost pure title compound in 70 % yield (2165 mg).