反应详情

A clear solution of 4-(3-amino-2,2-difluoropropylamino)-4-methyl-1-(2-nitro-1H-imidazol-1-yl)-3-pentanone oxime (title B compound) (0.40 g, 1.20 mmol) and N,N-diisopropylethylamine (0.42 g, 3.32 mmol) in acetonitrile (5 mL) was treated with 3-chloro-3-methyl-2-nitrosobutane (prepared analogously to 3-chloro-3-methyl-2-nitroisobutane, Example 1, step (B)) (0.45 g, 3.32 mmol) with stirring at room temperature under nitrogen atmosphere for 2 hours. After evaporation of the solvent under vacuum, the paste thus obtained was loaded, as a powder adsorbed on silica gel, onto a silica gel column and eluted with methanol-dichloromethane (2:98). The fractions with compound were pooled together and evaporated to afford the title product, which was further purified by crystallization from CH2Cl2—CH3OH to a cream colored solid. Yield; 0.45 g (88%); mp. 90-92° C.; 1H NMR (DMSO-d6) d 1.12 [s, 12H, C(CH3)2], 1.70[s, 3H, C(═NOH)CH3], 2.18 & 2.22 (2t, 2H, NH), 2.62 (m, 4H, CH2CF2), 2.80 (t, 2H, J=7.25 Hz, CH2CH2N), 4.61 (t, 2H, J=7.25 Hz, CH2CH2N), 7.15 & 7.52 (2s, 2H, imi-H) and 10.46 & 10.90 (2s, 2H, NOH). MS m/e 434 (M+H)+. Anal. Calcd for C17H29N7O4F2: C, 47.11; H, 7.74; N, 22.62; F, 8.77. Found: C, 47.28; H, 6.54; N, 22.79; F, 8.53.

1. customAfter evaporation of the solvent under vacuum
2. customthe paste thus obtained
3. washeluted with methanol-dichloromethane (2:98)
4. customevaporated