反应详情

2-(2-Amino-pyrimidin-4-yl)-1-methyl-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester (prepared as described in Example 9) (300 mg, 0.873 mmol) was suspended in dry pyridine under nitrogen atmosphere and sonicated for 2 minutes. 4-Methyl-thiophene-2-carbonyl chloride (0.142 mL, 1.135 mmol, 1.3 eq) and DMAP (10 mg, 0.087 mmol, 0.1 eq) were added and the mixture was stirred at room temperature for 3 hours. Pyridine was then evaporated and the residue was taken up with saturated aqueous NaHCO3 (10 mL) and extracted with ethyl acetate (3×10 mL). Combined organic layers were washed with brine (3×10 mL), dried over Na2SO4 and evaporated to dryness. The crude product was purified by chromatography on silica gel (gradient n-hexane/ethyl acetate 1:1 to pure ethyl acetate) to obtain 394 mg of 1-methyl-2-{2-[(4-methyl-thiophene-2-carbonyl)-amino]-pyrimidin-4-yl}-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester (85%).

1. customsonicated for 2 minutes
2. customPyridine was then evaporated
3. extractionextracted with ethyl acetate (3×10 mL)
4. washCombined organic layers were washed with brine (3×10 mL)
5. dry with materialdried over Na2SO4
6. customevaporated to dryness
7. customThe crude product was purified by chromatography on silica gel (gradient n-hexane/ethyl acetate 1:1 to pure ethyl acetate)