反应详情

A solution of 2-[3-(difluoromethyl)-5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]imidazo[4,5-d]dipyrido[2,3-b:4′,3′-f]azepin-3 (8H)-ol (1.94 g, 4.17 mmol) in N,N-dimethylacetamide (30 mL, 0.3226 mol) was heated at 160° C. for 2.5 hours with triisopropyl phosphite (4.0 mL, 0.0174 mol). The reaction was allowed to cool and then poured into 50 mL water. The reaction was extracted with ethyl acetate and the organic extracts were washed with water, saturated NaCl, dried (MgSO4) and concentrated in vacuo. The reaction was chromatographed on silica gel using 3% Et3N with ethyl acetate, and 3% MeOH/ethyl acetate to give the desired product. 1H NMR (CDCl3): δ 9.52 and 9.45 (brs, 1H), 7.87-8.11 (m, 4H), 6.74-7.61 (m, 3H), 6.10 and 6.13 (br s, 1H), 5.40 (dd, 1H), 4.11 (m, 1H), 3.71 (m, 1H), 2.80 (s, 3H), 2.44 (m, 1H), 2.17 (m, 1H), 1.95 (m, 1H), 1.60-1.80 (m, 3H). Mass spec(EI) m/z=450 (M+1).

1. temperatureto cool
2. extractionThe reaction was extracted with ethyl acetate
3. washthe organic extracts were washed with water, saturated NaCl
4. dry with materialdried (MgSO4)
5. concentrationconcentrated in vacuo
6. customThe reaction was chromatographed on silica gel using 3% Et3N with ethyl acetate, and 3% MeOH/ethyl acetate