Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:17])([S:13](F)(=[O:15])=[O:14])[C:3]([F:12])([F:11])[C:4]([F:10])([F:9])[C:5]([F:8])([F:7])[F:6].C(OC(C)C)(C)C.[CH2:25]([NH2:27])[CH3:26]>S(=O)(=O)(O)O>[CH2:25]([NH:27][S:13]([C:2]([F:17])([F:1])[C:3]([F:12])([F:11])[C:4]([F:10])([F:9])[C:5]([F:8])([F:7])[F:6])(=[O:15])=[O:14])[CH3:26]
Reactant: CCN
Reactant: O=S(=O)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Agent: O=S(=O)(O)O
Solvent: CC(C)OC(C)C
Product: CCNS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Temperature: 60 °C
Reaction time: 8 h

Procedure:
N-ethyl-perfluorbutanesulfonamide (C4F9SO2N(H)CH2CH3) was prepared by placing 302 grams perfluorobutanesulfonyl fluoride and 500 mL diisopropyl ether in a two liter three-necked round bottom flask under nitrogen. Next 139.5 grams ethylamine (3.1 equivalents) was slowly added while keeping the temperature below 60° C. After addition was complete the reaction mixture was stirred at 60° C. overnight. Next, 500 milliliters of 6 M sulfuric acid was added. The organic layer was isolated and washed two times with equal volumes of water. The solvent was removed under reduced pressure the give the sulfonamide. The sulfonamides with varying Rf were prepared using this procedure but with the appropriate perfluoroalkanesulfonyl fluoride. The corresponding epoxides were prepared from these sulfonamides in the same manner as described in example 1.
Reaction SMILES: C([O:8][C:9]([C:11]1[CH:12]=[C:13]([NH:17][C:18](=[O:50])[NH:19][CH2:20][C:21]([N:23]2[CH:27]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:26]([S:34]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)(=[O:36])=[O:35])[CH2:25][CH:24]2[C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])=[O:22])[CH:14]=[CH:15][CH:16]=1)=[O:10])C1C=CC=CC=1>C(O)C.[Pd]>[C:46]([O:45][C:43]([CH:24]1[CH2:25][CH:26]([S:34]([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)(=[O:35])=[O:36])[CH:27]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:23]1[C:21](=[O:22])[CH2:20][NH:19][C:18](=[O:50])[NH:17][C:13]1[CH:12]=[C:11]([CH:16]=[CH:15][CH:14]=1)[C:9]([OH:10])=[O:8])=[O:44])([CH3:49])([CH3:47])[CH3:48]
Reactant: CC(C)(C)OC(=O)C1CC(S(=O)(=O)c2ccccc2)C(c2ccccc2)N1C(=O)CNC(=O)Nc1cccc(C(=O)OCc2ccccc2)c1
Agent: [Pd]
Solvent: CCO
Product: CC(C)(C)OC(=O)C1CC(S(=O)(=O)c2ccccc2)C(c2ccccc2)N1C(=O)CNC(=O)Nc1cccc(C(=O)O)c1
Yield: 66.5 %

Procedure:
A The reaction is carried out in a way analogous to that described in Example 2A, but from 1.9 g of tert-butyl (2RS,4RS,5RS)-1-{2-[3-(3-(benzyloxycarbonyl)phenyl)ureido]acetyl}-5-phenyl-4-(phenylsulphonyl)pyrrolidine-2-carboxylate and 0.2 g of 10% palladium-on-charcoal in 75 cm3 of ethanol. After treatment, there are obtained 1.1 g of (2RS,4RS,5RS)-3-{3-[2-(2-tert-butoxycarbonyl-5-phenyl-4-phenylsulphonyl-1-pyrrolidinyl)-2-oxoethyl]ureido}benzoic acid [Rf =0.22; eluent: methylene chloride/methanol (80/20)].
Reaction SMILES: [I:1][C:2]1[C:7]([CH3:8])=[C:6]([I:9])[C:5]([CH3:10])=[C:4]([I:11])[C:3]=1[CH3:12].C([O:16][C:17](=[O:19])[CH3:18])(=O)C.S(=O)(=O)(O)O.[Mn]([O-])(=O)(=O)=O.[K+]>C(O)(=O)C>[I:1][C:2]1[C:3]([CH2:12][O:19][C:17](=[O:16])[CH3:18])=[C:4]([I:11])[C:5]([CH2:10][O:19][C:17](=[O:16])[CH3:18])=[C:6]([I:9])[C:7]=1[CH2:8][O:16][C:17](=[O:19])[CH3:18]
Reactant: CC(=O)OC(C)=O
Reactant: Cc1c(I)c(C)c(I)c(C)c1I
Agent: O=[Mn](=O)(=O)[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Solvent: CC(=O)O
Product: CC(=O)OCc1c(I)c(COC(C)=O)c(I)c(COC(C)=O)c1I
Reaction time: 16 h

Procedure:
Triiodomesitylene (19.5 g, 39 mmol) was added to glacial acetic acid (200 ml) containing acetic anhydride (400 ml) and concentrated sulfuric acid (40 ml). Solid potassium permanganate (24.6 g, 156 mmol) was then added in small portions over a period of 3 h. After stirring for 16 h, the solvent was evaporated and water (200 ml) is was added. The aqueous suspension was extracted with dichloromethane (250 ml) and the organic phase was washed with water (3×50 ml), dried (MgSO4) and evaporated. The solid residue was suspended in acetone and the white crystalline product was collected by filtration. Yield: 9.3 g (35%).
Reaction SMILES: [CH3:1][S:2][C:3]1[S:4][C:5]2[CH:11]=[C:10]([CH2:12][NH:13][C:14]3[C:15]([NH2:24])=[CH:16][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:19]=3)[CH:9]=[CH:8][C:6]=2[N:7]=1.[CH:25](OCC)(OCC)OCC>C(O)=O>[CH3:1][S:2][C:3]1[S:4][C:5]2[CH:11]=[C:10]([CH2:12][N:13]3[C:14]4[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:21])[F:22])=[CH:16][C:15]=4[N:24]=[CH:25]3)[CH:9]=[CH:8][C:6]=2[N:7]=1
Reactant: CCOC(OCC)OCC
Reactant: CSc1nc2ccc(CNc3ccc(C(F)(F)F)cc3N)cc2s1
Solvent: O=CO
Product: CSc1nc2ccc(Cn3cnc4cc(C(F)(F)F)ccc43)cc2s1
Temperature: 100 °C
Yield: 69 %

Procedure:
A stirred mixture of N1-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-4-(trifluoromethyl)benzene-1,2-diamine (0.32 g, 0.86 mmol) from the previous step, formic acid (0.5 mL) and triethyl orthoformate (5 mL) was heated at 100° C. for 1 h. The reaction mixture was cooled to rt and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with 3% MeOH in DCM to afford 2-(methylthio)-6-((5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazole (0.22 g, 69%) as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 8.12 (s, 1H), 8.08 (s, 1H), 7.84 (d, J=8.4 Hz, 1H), 7.48-7.54 (m, 2H), 7.36 (d, J=8.4 Hz, 1H), 7.26 (m, 1H), 5.49 (s, 2H), 2.78 (s, 3H); LCMS (ESI) m/z 380 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([O:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[C:18]([Cl:26])[CH:17]=3)[CH:10]=2)[CH:5]=[CH:4][C:3]=1[C:27]([F:30])([F:29])[F:28].[N+:31]([O-])([OH:33])=[O:32].S(=O)(=O)(O)O.CCCCCC>O.C1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N+:31]([O-:33])=[O:32])=[C:11]([O:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:23])([F:24])[F:25])=[C:18]([Cl:26])[CH:17]=3)[CH:10]=2)[CH:5]=[CH:4][C:3]=1[C:27]([F:30])([F:28])[F:29]
Reactant: O=[N+]([O-])O
Reactant: FC(F)(F)c1ccc(Oc2cccc(Oc3ccc(C(F)(F)F)c(Cl)c3)c2)cc1Cl
Agent: O=S(=O)(O)O
Solvent: c1ccccc1
Solvent: O
Solvent: CCCCCC
Product: O=[N+]([O-])c1ccc(Oc2ccc(C(F)(F)F)c(Cl)c2)cc1Oc1ccc(C(F)(F)F)c(Cl)c1

Procedure:
1,3-Bis(2-chloro-α,α,α-trifluoro-p-tolyloxy)-benzene (12 g. 0.0255 mole) is added to a mixture of concentrated nitric acid (12 g.) and sulfuric acid (15 g.) at 5° C. The temperature is then allowed to rise to 25°-30° C. with manual stirring and mild ice bath cooling and after 10-20 minutes, the oil solidifies. The mixture is taken up in water/benzene (400 ml)/hexane (400 ml) and the organic phase is washed with water, dried, filtered through activated silica gel (~20 g.), and the solvents removed. The residue is recrystallized from isopropanol to give 1,3-bis(2-chloro-α,α,α-trifluoro-p-tolyloxy)-4-nitrobenzene, (7.4 g. 56%) m.p. 110°-111.5° C.
Reaction SMILES: C[Si]([N-:5][Si](C)(C)C)(C)C.[Li+].Cl[CH:12]([B:16]1[O:20][C:19]([CH3:22])([CH3:21])[C:18]([CH3:24])([CH3:23])[O:17]1)[CH2:13][CH:14]=[CH2:15].[F:25][C:26]([F:31])([F:30])[C:27]([OH:29])=[O:28]>O1CCCC1>[F:25][C:26]([F:31])([F:30])[C:27]([OH:29])=[O:28].[CH2:13]([CH:12]([B:16]1[O:20][C:19]([CH3:22])([CH3:21])[C:18]([CH3:24])([CH3:23])[O:17]1)[NH2:5])[CH:14]=[CH2:15]
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Reactant: C=CCC(Cl)B1OC(C)(C)C(C)(C)O1
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O=C(O)C(F)(F)F
Product: C=CCC(N)B1OC(C)(C)C(C)(C)O1
Temperature: 25 °C
Reaction time: 8 h
Yield: 24.4 %

Procedure:
6.6 ml (6.6 mmol) of 1M lithium bis(trimethylsilyl)amide in tetrahydrofuran were added dropwise to a solution of 1.43 g (6.6 mmol) of 2-(1(RS)-chloro-3-butenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in 20 ml of tetrahydrofuran under nitrogen at -78° C. The solution was then stirred overnight at room temperature. The solvent was removed by evaporation and the residue was taken up in diethyl ether. Insoluble material was removed by filtration and the filtrate was cooled to 0° C. 1.5 ml (19.8 mmol) of trifluoroacetic acid were added and thesolution was stirred at 0° C. for 30 minutes. The resulting precipitate was filtered off and dried to give 0.5 g of α-(RS)-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-methylamine trifluoroacetate which was used in the next step without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]=2[NH:12][C:11](=[S:20])[CH2:10][N:9]=1.[H-].[Na+].[CH3:23][N:24]([CH2:26][CH2:27][CH2:28]Cl)[CH3:25].O>CN(C)C=O>[CH3:23][N:24]([CH3:25])[CH2:26][CH2:27][CH2:28][S:20][C:11]1[CH2:10][N:9]=[C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])[C:14]2[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]=2[N:12]=1
Reactant: CN(C)CCCCl
Reactant: S=C1CN=C(c2ccccc2Cl)c2cc(Cl)ccc2N1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CN(C)CCCSC1=Nc2ccc(Cl)cc2C(c2ccccc2Cl)=NC1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
To a solution of 6.4 g of 1,3-dihydro-5-(2-chlorophenyl)-7-chloro-2H-1,4-benzodiazepine-2-thione in 50 ml of anhydrous dimethylformamide is added under cooling with stirring 1,2 g of sodium hydride (50% oily suspension), and the resulting mixture is stirred at room temperature for 20 minutes. To the mixture is added dropwise 7.6 g of N,N-dimethyl-3-chloropropylamine and the mixture is stirred at room temperature for 1.5 hours. The reaction mixture is poured into iced water and extracted with ethyl acetate. The extract is washed with water and dried over magnesium sulfate and, thereafter, the solvent is distilled off under reduced pressure. An oily product obtained as the residue is subjected to column chromatography on alumina and eluted from the column with a benzenechloroform mixture. The eluate is treated according to usual procedure to obtain an oily 2-(3-dimethylaminopropylthio)-5-(2-chlorophenyl)-7-chloro-3H-1,4-benzodiazepine. The oily product thus obtained is treated, according to usual procedure, with fumaric acid and recrystallized from anhydrous ethanol and acetone to obtain 4.3 g of 2-(3-dimethylaminopropylthio)-5-(2-chlorophenyl)-7-chloro-3H-1,4-benzodiazepine fumarate, m.p. 154°- 156° C.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[O:10][C:11]1[CH:12]=[CH:13][C:14]2[O:18][C:17]([CH2:19]O)=[CH:16][C:15]=2[CH:21]=1.CCN(C(C)C)C(C)C.S(Cl)([Cl:33])=O>C(Cl)Cl>[Cl:33][CH2:19][C:17]1[O:18][C:14]2[CH:13]=[CH:12][C:11]([O:10][C:2]3[S:1][C:5]4[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=4[N:3]=3)=[CH:21][C:15]=2[CH:16]=1
Reactant: OCc1cc2cc(Oc3nc4ccccc4s3)ccc2o1
Reactant: O=S(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: ClCc1cc2cc(Oc3nc4ccccc4s3)ccc2o1
Temperature: 25 °C
Reaction time: 2 h
Yield: 83.3 %

Procedure:
To a solution of [5-(benzothiazol-2-yloxy)-benzofuran-2-yl]-methanol (55 mg, 0.19 mmol) and DIEA (0.042 mL, 34 mg, 0.24 mmol) in DCM (0.8 mL) was added thionyl chloride (0.017 mL, 26 mg, 0.22 mmol) and the resulting mixture was stirred (rt, 2 h). The reaction mixture was concentrated under a stream of nitrogen to afford the title compound (50 mg, 100%). MS (ESI): mass calcd for C16H10NO2SCl, 315.0; m/z found 316.1 [M+H]+.
Reaction SMILES: [CH2:1]([NH:8][CH2:9][CH:10]([NH:20][CH:21]([CH:29]([CH3:31])[CH3:30])[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.Cl[C:40](Cl)([O:42]C(=O)OC(Cl)(Cl)Cl)Cl>C1(C)C=CC=CC=1>[CH2:1]([N:8]1[CH2:9][CH:10]([CH2:11][C:12]2[CH:13]=[CH:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=2)[N:20]([CH:21]([CH:29]([CH3:31])[CH3:30])[C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])[C:40]1=[O:42])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc(CC(CNCc2ccccc2)NC(C(=O)OC(C)(C)C)C(C)C)cc1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: COc1ccc(CC2CN(Cc3ccccc3)C(=O)N2C(C(=O)OC(C)(C)C)C(C)C)cc1
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 32 %

Procedure:
t-Butyl 2-(2-benzylamino-1-(4-methoxybenzyl)ethylamino)-3-methylbutyrate (0.64 g; 1.5 mmol) was dissolved in toluene (40 ml). Triethylamine (457 μL; 3.3 mmol) and triphosgene (0.49 g; 1.65 mmol) were added. The reaction mixture was stirred at RT for 4.5 h. It was then washed with water (1×), saturated NaHCO3 solution (1×) and again with water (1×). The organic phase was dried over Na2SO4 and concentrated in a rotary evaporator. The crude product was chromatographed on an SiO2 cartridge (EtOAc/n-heptane 1:3). t-Butyl 2-(3-benzyl-5-(4-methoxybenzyl)-2-oxoimidazolidin-1-yl)-3-methylbutyrate (0.22 g, 0.48 mmol) was obtained as a yellow oil. MS: 453.20 (M+H); Rt: 1.94 min (method: gradient 0 min 96% H2O (0.05% TFA) 2.0 min 95% acetonitrile, 95% acetonitrile to 2.4 min, 4% acetonitrile 2.45 min; flow rate 1 ml/min; column 0.4 μL (YMC J'sphere ODS H80 20X2 1.4μ); 30° C.)
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][CH2:10][NH:9]2)=[CH:4][CH:3]=1.[C:13]1([S:19](Cl)(=[O:21])=[O:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>>[C:13]1([S:19]([N:9]2[CH2:10][CH2:11][CH2:12][CH:8]2[C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)(=[O:21])=[O:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: Clc1ccc(C2CCCN2)cc1
Reactant: O=S(=O)(Cl)c1ccccc1
Product: O=S(=O)(c1ccccc1)N1CCCC1c1ccc(Cl)cc1

Procedure:
The title compound, white solid, m.p. 122° C. and MS: m/e=321 (M+) was prepared in accordance with the general method of example 1e from (RS)-2-(4-chloro-phenyl)-pyrrolidine and benzenesulfonyl chloride.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH2:10][CH:11]=[O:12])[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:13]([Mg]Br)[CH2:14][CH:15]([CH3:17])[CH3:16].C(Br)CC(C)C.[Mg].[Cl-].[NH4+]>O1CCCC1>[C:1]([O:5][C:6]([N:8]([CH2:10][CH:11]([OH:12])[CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)CC[Mg]Br
Reactant: CN(CC=O)C(=O)OC(C)(C)C
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CC(C)CCBr
Product: CC(C)CCC(O)CN(C)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of N-t-butoxycarbonylsarcosinal (3.46 g) in dry tetrahydrofuran (100 ml) which was cooled to -78° C., was added dropwise a solution of isopentylmagnesium bromide prepared from isopentyl bromide (30.8 g) and magnesium (4.86 g) in dry tetrahydrofuran (200 ml). After the addition was complete, the reaction mixture was allowed to warm to ambient temperature and stirred at the same temperature for 4 hours. After saturated aqueous ammonium chloride (200 ml) was added thereto, the resulting mixture was extracted with diethyl ether (300 ml×2). The combined extract was dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified with silicagel column chromatography (20% ethyl acetate in n-hexane as eluent) to give 1-(N-t-butoxycarbonyl-N-methylamino)-2-hydroxy-5-methylhexane (3.96 g).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:13])=[N:11][N:12]=2)=[CH:4][C:3]=1[C:14]1[CH:19]=[CH:18][C:17]([C:20](O)=[O:21])=[CH:16][CH:15]=1.[NH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.C(Cl)Cl>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:13])=[N:11][N:12]=2)=[CH:4][C:3]=1[C:14]1[CH:15]=[CH:16][C:17]([C:20]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:21])=[CH:18][CH:19]=1
Reactant: Cc1nnc(-c2ccc(C)c(-c3ccc(C(=O)O)cc3)c2)o1
Reactant: Nc1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: Cc1nnc(-c2ccc(C)c(-c3ccc(C(=O)Nc4ccccc4)cc3)c2)o1
Temperature: 25 °C
Reaction time: 4 h
Yield: 51 %

Procedure:
2′-Methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-1,1′-biphenyl-4-carboxylic acid (50 mg, 0.17 mmol), aniline (16 mg, 0.17 mmol) and 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (33 mg, 0.17 mmol) and DMF (20 drops) were suspended in dry DCM (5 ml) and stirred at room temperature under nitrogen for 4 h. The mixture was absorbed onto an SPE (silica, 10 g), eluted with DCM and then with a DCM/ethanol/ammonia gradient (250:8:1 to 100:8:1). The solvent was evaporated from the product fractions under vacuum to yield 2′-methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-N-phenyl-1,1′-biphenyl-4-carboxamide as a white solid (32 mg, 51%). NMR; δH [2H6]—DMSO 10.34,(1H, b), 8.06,(2H, d), 7.91,(1H, dd), 7.80,(3H, m), 7.57,(3H, m), 7.36,(2H, t), 7.11,(1H, t), 2.57,(3H, s), 2.34,(3H, s). LCMS; retention time 3.39 min, MH+ 370.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][NH2:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[CH:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][C:17]=1[S:26](Cl)(=[O:28])=[O:27]>C(Cl)Cl>[N:1]1([CH2:6][CH2:7][NH:8][S:26]([C:17]2[CH:18]=[CH:19][C:20]3[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:16]=2)(=[O:28])=[O:27])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: NCCN1CCCC1
Reactant: O=S(=O)(Cl)c1ccc2ccccc2c1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=S(=O)(NCCN1CCCC1)c1ccc2ccccc2c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 68.1 %

Procedure:
To an ice-cooled solution of 2-pyrrolidin-1-yl-ethylamine (1.00 g, 8.76 mmol) and triethylamine (1.22 ml, 8.76 mmol) in DCM (20 ml) was added portionwise 2-naphthalenesulfonyl chloride (1.98 g, 8.73 mmol). The coolant was removed and the resultant solution was stirred at ambient temperature for 16 h. The organic phase was washed sequentially twice with water (20 ml) and brine (20 ml), and dried over anhydrous magnesium sulfate. The filtrate was evaporated at reduced pressure to obtain the title compound as a white solid (1.81 g, 68%). 1HNMR 8.45 (1H, d, 1.5), 7.99-7.83 (4H, m), 7.66-7.61 (2H, m), 5.80-5.20 (1H, br s), 3.06-3.02 (2H, m), 2.53 (2H, m), 12.36-2.32 (4H, m), 1.74-1.65 (4H, m). Microanalysis found C 62.96 H 6.74; N 9.11. C16H20N2O2S requires C 63.13 H 6.62 N 9:20.
Reaction SMILES: [F:1][CH2:2][C:3]([O:5]CC)=O.[Cl:8][C:9]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:10]=1[CH2:11][Mg]Cl>C(OCC)C.[Cl-].[NH4+]>[Cl:8][C:9]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:10]=1[CH2:11][C:3](=[O:5])[CH2:2][F:1]
Reactant: Cl[Mg]Cc1ccc(Cl)cc1Cl
Reactant: CCOC(=O)CF
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Product: O=C(CF)Cc1ccc(Cl)cc1Cl
Temperature: -60 °C
Reaction time: 5 h
Yield: 49 %

Procedure:
To a stirred solution of ethyl fluoroacetate (0.33 ml; 3.3 mmol) in dry diethyl ether (3.3 ml) under argon at −76° C. was added dropwise a 0.25 M solution of 2,4-dichlorobenzylmagnesium chloride in diethyl ether (20 ml; 5 mmol). The suspension was stirred at −60° C. during 5 h. The mixture was poured in ammonium chloride sat. solution and extracted three times with diethylether. Organics were combined, dried over sodium sulfate and evaporated to a resin which was subject to flash chromatography (eluant: c-hexane/ethyl acetate 99:1 to 70:30) to afford 0.36 g (49% of theory) of 1-(2,4-dichloro-phenyl)-3-fluoro-propan-2-one as a pale yellow solid (melting point: 48-52° C.).
Reaction SMILES: C([O:4][C@@H:5]1[C@@H:10]([O:11]C(=O)C)[C@H:9]([O:15]C(=O)C)[C@@H:8]([CH2:19][O:20]C(=O)C)[O:7][C@H:6]1[N:24]1C(=O)C(=CC2C=CC=CC=2)S[C:25]1=[S:37])(=O)C.[NH3:38]>CO>[C@@H:6]1([NH:24][C:25]([NH2:38])=[S:37])[O:7][C@H:8]([CH2:19][OH:20])[C@@H:9]([OH:15])[C@H:10]([OH:11])[C@H:5]1[OH:4]
Reactant: CC(=O)OC[C@H]1O[C@@H](N2C(=O)C(=Cc3ccccc3)SC2=S)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: N
Solvent: CO
Product: NC(=S)N[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Temperature: 25 °C
Reaction time: 18 h

Procedure:
N-(2,3,4,6-Tetra-O-acetyl-β-D glucopyranosyl)-5-benzylidenerhodanine(5.52 g., 0.01 mole) was added to a solution of 50 ml. of methanol saturated with ammonia at 0° in a pressure bottle. The mixture was stirred at room temperature for 18 hours with the stopper well closed. The mixture was evaporated to a syrupy material below 30° in vacuo. The residue was dissolved in the minimum amount of methanol and passed through a silica gel column(2.54×15 cm) with aid of additional methanol. One hundred ml. of effluent was collected and concentrated. During the concentration, a precipitate was formed. The white precipitate was filtered and dried at room temperature in vacuo, yielding 2.04 g. (86.8%); m.p. 207°-209°(dec.). (Lit. m.p. 207°-210°(83), m.p. 211°-212°(32), m.p. 205°-207°(86).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[NH:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1>C(#N)C>[F:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[N:5]([CH2:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1)[CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:16])[CH3:17])=[O:13])[CH2:8][CH2:7]1
Reactant: CC(C)(C)OC(=O)N1CCC(Nc2cccc(F)c2)CC1
Reactant: Fc1ccc(CBr)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CC(C)(C)OC(=O)N1CCC(N(Cc2ccc(F)cc2)c2cccc(F)c2)CC1
Yield: 89 %

Procedure:
Tert-butyl 4-(3-fluoroanilino)-1-piperidinecarboxylate 1 (20 g) was dissolved in acetonitrile (250 ml). Potassium carbonate (33.2 g) and 1-(bromomethyl)-4-fluorobenzene (11 ml) were added to the solution. The reaction mixture was heated at reflux overnight, then cooled, concentrated and the residue was taken up in dichloromethane and water. The aqueous layer was washed twice with dichloromethane. The combined organic layers were dried over MgSO4 and concentrated. The resulting white solid was triturated in hexane and filtered off to afford tert-butyl 4-[3-fluoro(4-fluorobenzyl)anilino]-1-piperidinecarboxylate 8 (25.5 g).
Reaction SMILES: [CH:1]1([C:4]2[NH:5][C:6]3[C:12]([CH2:13][OH:14])=[CH:11][CH:10]=[C:9]([O:15][CH3:16])[C:7]=3[N:8]=2)[CH2:3][CH2:2]1>C1(C)C=CC=CC=1.ClCCl.[O-2].[O-2].[Mn+4]>[CH:1]1([C:4]2[NH:5][C:6]3[C:12]([CH:13]=[O:14])=[CH:11][CH:10]=[C:9]([O:15][CH3:16])[C:7]=3[N:8]=2)[CH2:2][CH2:3]1
Reactant: COc1ccc(CO)c2[nH]c(C3CC3)nc12
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: COc1ccc(C=O)c2[nH]c(C3CC3)nc12
Temperature: 85 °C
Reaction time: 3 h

Procedure:
A stirred suspension of 2-cyclopropyl-7-methoxy-3 H-benzimidazole-4-methanol in a mixture of toluene (250 ml) and dichloromethane (150 ml), at room temperature and under nitrogen, was treated portionwise with activated manganese dioxide (11 g). The resulting suspension was stirred under nitrogen at 85° C. for 3 hours. The suspension was allowed to cool slightly and was then filtered through hyflosupercel washing the filter pad six times with hot ethyl acetate (50 ml). The combined filtrate and washings were dried over magnesium sulphate and then evaporated to yield the title compound as a cream coloured powder (7.26 g).
Reaction SMILES: [NH2:1][C:2]1[C:11]2=[CH:12][N:13]([C@@H:15]3[O:21][C@H:20]([CH2:22][OH:23])[C@@H:18]([OH:19])[C@@:16]3(C)[OH:17])[N:14]=[C:9]3[C:10]2=[C:4]([C:5](=[O:25])[NH:6][N:7]=[CH:8]3)[CH:3]=1>C(Cl)(=O)C>[NH2:1][C:2]1[C:11]2=[CH:12][N:13]([C@@H:15]3[O:21][C@H:20]([CH2:22][O:23][C:5](=[O:25])[CH3:4])[C@@H:18]([O:19][C:18](=[O:19])[CH2:20][CH3:22])[C@H:16]3[O:17][C:16](=[O:17])[CH3:15])[N:14]=[C:9]3[C:10]2=[C:4]([C:5](=[O:25])[NH:6][N:7]=[CH:8]3)[CH:3]=1
Reactant: C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1n1cc2c(N)cc3c(=O)[nH]ncc(n1)c23
Solvent: CC(=O)Cl
Product: CCC(=O)O[C@H]1[C@@H](OC(C)=O)[C@H](n2cc3c(N)cc4c(=O)[nH]ncc(n2)c34)O[C@@H]1COC(C)=O

Procedure:
To a mixture of the product from Example 14 (100 mg, 0.28 mmol) in acetyl chloride/glacial acetic acid (3 mL, 1:2, v/v) is stirred at room temperature until disappearance of the starting nucleoside, as judged by TLC. The mixture is evaporated in vacuo to dryness and purified on silica gel column.