Triethylamine → (S)-Ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(hydroxymethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (S)-7-(4-(allyloxy)-4-methylpiperidin-1-yl)-6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acid (2.443 g, 5 mmol) and Et3N (0.836 ml, 6.00 mmol) in THF (100 mL) was added 1M isopropyl chloroformate/toluene (6.00 ml, 6.00 mmol) at 0° C. After 1 h, a solution of NaBH4 (0.567 g, 15.00 mmol) in cold water (20 mL) was added at once and stirred for at 0° C. LCMS after 1 h showed formation of desired product and presence of unreacted mixed unhydride intermediate. So, added additional NaBH4 (0.284 g, 7.5 mmol) and continued stirring for 3 h while allowing reaction mixture to slowly warm to 10° C. LCMS at this point showed still remaining about 10% unreacted material. So, added additional NaBH4 (0.189 g) and stirred for 1 h at 10° C. Then the reaction was quenched with AcOH (1 mL), diluted with Et2O (200 mL), washed with water (2×50 mL) and brine (25 mL). The organic layer dried (MgSO4), filtered and concentrated to give (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(hydroxymethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (2.7 g, 5.12 mmol, 102% yield, 90% purity) as pale yellow paste which was used in next step without purification. LCMS (M+H)=475.2.

Provenance & Evidence