反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
CONDITIONS
反应条件
- 温度
- 100 °C
PROCEDURE
实验过程
A mixture of tert-butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (500 mg, 0.998 mmol), 1-(difluoromethyl)-1H-pyrazol-4-ylboronic acid (808 mg, 4.99 mmol), bis(triphenylphosphine)palladium chloride (70.1 mg, 0.100 mmol) in dioxane (15 mL) and 2M saturated sodium carbonate (2 mL) were heated to 100° C. in a microwave for 30 min. The solution was concentrated and was purified by preparatory HPLC eluting with water (10 mM NH4HCO3) and ACN/water (80/20 v/v, 15-30% gradient, 10 mM NH4HCO3) to give the title compound as a white solid (132 mg, 23%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.35 (s, 9H), 1.52 (s, 9H), 1.55-1.56 (m, 1H), 2.46-2.47 (m, 1H), 3.57-3.59 (m, 2H), 3.81-3.84 (m, 3H), 4.61-4.62 (m, 1H), 4.78 (s, 2H), 6.61 (d, J=6.35 Hz, 1H), 7.15 (d, J=6.83 Hz, 1H), 7.97 (s, 1H), 8.54 (s, 1H), 9.24 (s, 1H). [M+H] calc'd for C26H33F3N6O6, 583. found, 583.
WORKUP
后处理
- concentrationThe solution was concentrated
- customwas purified by preparatory HPLC
- washeluting with water (10 mM NH4HCO3) and ACN/water (80/20 v/v, 15-30% gradient, 10 mM NH4HCO3)