反应详情

温度

40 °C

To a solution of 5-butyl-3-iodo-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one (5 g, 15.72 mmol) and (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (10.43 g, 23.58 mmol) in anhydrous DMF (250 mL) at room temperature under a nitrogen atmosphere was added 1,8-diazabicyclo[5.4.0]undec-7-ene (4.23 mL, 28.3 mmol) and the reaction mixture was stirred for 2.5 hours. (3,4-Dimethoxyphenyl)methanamine (20 mL, 94 mmol) was added and the mixture was warmed to 40° C. for 3 hours. The reaction mixture was evaporated in-vacuo and the resulting oil partitioned between ethyl acetate and water. The organic layer was separated, washed with brine, dried over MgSO4, filtered and evaporated in-vacuo to yield as a semi-crystalline yellow oil (23.7 g). The residue was absorbed onto Florosil, loaded onto a 330 g silica pre-conditioned cartridge and purified by chromatography using cyclohexane over 1 column volume followed by 0-100% ethyl acetate in cyclohexane gradient over 14 column volumes followed by ethyl acetate over 4 column volumes. Appropriate fractions containing only the desired material by LC-MS analysis were combined and evaporated in-vacuo to yield the title compound as a pale yellow foam (4.58 g).

1. customThe reaction mixture was evaporated in-vacuo
2. customthe resulting oil partitioned between ethyl acetate and water
3. customThe organic layer was separated
4. washwashed with brine
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. customevaporated in-vacuo