2-methyl-5-[[(2S)-oxiran-2-yl]methoxy]-1,3-benzothiazole → (2S)-3-((2S)-4-{[5-(2-fluorophenyl)isoxazol-3-yl]methyl}-2-methylpiperazinyl)-1-(2-methylbenzothiazol-5-yloxy)propan-2-ol

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (2S)-methylpiperazine (40 mg, 0.40 mmol) in ethanol (5 mL) was added 3-chloromethyl-5-(2-fluorophenyl)isoxazole (42 mg, 0.20 mmol) and triethylamine (60μL, 0.43 mmol). The resulting mixture was stirred at 80° C. for 8 hours. It was then cooled, concentrated, and purified by preparative chromatography (1:9 methanol:methylene chloride) to yield 3-[((3S)-3-methylpiperazinyl)methyl]-5-(2-fluorophenyl)isoxazole (30 mg, M+1=276.14). B. To a solution of 3-[((3S)-3-methylpiperazinyl)methyl]-5-(2-fluorophenyl)isoxazole (28 mg, 0.10 mmol) in tert-amylalcohol (5 mL) was added 5-[((2S)oxiran-2-yl)methoxy]-2-methylbenzothiazole (22 mg, 0.10 mmol). The reaction mixture was stirred at 95° C. for 1 day. It was then cooled, concentrated, and purified by preparative chromatography (1:19 methanol:methylene chloride) to afford (2S)-3-((2S)-4-{[5-(2-fluorophenyl)isoxazol-3-yl]methyl}-2-methylpiperazinyl)-1-(2-methylbenzothiazol-5-yloxy)propan-2-ol (19 mg, M+1=497.27).

Provenance & Evidence