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-nitrosobutane, 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 absorbed 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(CH32], 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. HPLC: Retention time: 20.74 min [Microsorb-C18, 0.46×25 cm, 5 m; solvent; 0.1% trifluoroacetic acid (TFA)/water (A) and 0.1% TFA/acetonitrile (B); flow rate: 1.0 mL/min.; run condition: linear gradient, 1% increase in B per min.; ran at 230 and 254 nm for 50 min.; in both cases a single peak was observed; 98.95% (230 nm) and 100% (254 nm)].

1. customAfter evaporation of the solvent under vacuum
2. customthe paste thus obtained
3. customabsorbed on silica gel, onto a silica gel column
4. washeluted with methanol-dichloromethane (2:98)
5. customevaporated