反应详情

To a of −30° C. cooled solution of 7.40 g (17.6 mmol) (7R,8R,9R)-10-acetyl-7-hydroxy-2-methyl-9-phenyl-8-pivaloyloxy-7.8.9.10-tetrahydroimidazo[1.2-h][1.7]naphthyridine in dichloromethane (25 ml) and N-methyl-pyrrolidinone (25 ml) is added 4.00 g (19.3 mmol) methoxyethyl triflate and 1.40 g (35.2 mmol) sodium hydride and it is stirred for further 2 h at this temperature. The reaction is quenched by adding of saturated aqueous ammonium chloride solution. Subsequently the mixture is extracted twice with dichloromethane. The combined organic layers are washed with brine, dried over sodium sulphate and evaporated in vacuo. The crude product is purified by column chromatography (ethyl acetate/cyclohexane/triethylamine: 5/4/1) to give 7.50 g (15.63 mmol/89%) of the title compound as a yellow amorphous solid. 1H-NMR (200 MHz, [D6] DMSO): δ=1.19(s, 9H), 2.15(s, 3H), 2.38(s, 3H), 3.27(s, 3H), 3.45–3.57(m, 2H), 3.83–3.93(m, 2H), 4.60(d, 1H), 5.31(t, 1H), 5.79(d, 1H), 6.94 (s, 1H), 7.20(s, 5H); 7.74(s, 1H), 8.43(d, 1H).

1. customThe reaction is quenched
2. additionby adding of saturated aqueous ammonium chloride solution
3. extractionSubsequently the mixture is extracted twice with dichloromethane
4. washThe combined organic layers are washed with brine
5. dry with materialdried over sodium sulphate
6. customevaporated in vacuo
7. customThe crude product is purified by column chromatography (ethyl acetate/cyclohexane/triethylamine: 5/4/1)