反应详情

7-[[(7R)-8-Cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid 1q (140 mg, 0.346 mmol), (trans)-4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexanamine 16b (76 mg, 0.35 mmol), O-(benzotriazol-1-yl)-N,N,N′,N′-tetra methyluronium tetrafluoroborate (102 mg, 0.32 mmol) and diisopropylethylamine (103 mg, 0.80 mmol) were dissolved in 25 mL of dichloromethane. The reaction solution was stirred for 2 hours. The resulting solution was added dropwise with saturated sodium bicarbonate solution to adjust pH to 8 to 9 and extracted with dichloromethane (50 mL×3). The combined organic phase was washed with water (20 mL) and saturated sodium chloride solution (20 mL) successively, then dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-[(trans)-4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexyl]-2,3-dihydrobenzofuran-4-carboxamide 34 (50 mg, yield: 40.0%) as a white solid.

1. extractionextracted with dichloromethane (50 mL×3)
2. washThe combined organic phase was washed with water (20 mL) and saturated sodium chloride solution (20 mL) successively
3. dry with materialdried over anhydrous magnesium sulfate
4. filtrationfiltered
5. concentrationthe filtrate was concentrated under reduced pressure
6. customThe resulting residue was purified by silica gel column chromatography