Triethylamine → (S)-ethyl 2-(tert-butoxy)-2-(7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-2-(hydroxymethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acid (900 mg, 1.143 mmol) and Et3N (0.207 mL, 1.487 mmol) in THF (20 mL) was added 1M isopropyl chloroformate/toluene (1.487 mL, 1.487 mmol) at 0° C. After 1 h, a solution of NaBH4 (216 mg, 5.72 mmol) in cold water (20 mL) was added at once and stirred for additional 1 h at 0° C. Then the reaction was quenched with MeOH (1 mL), diluted with Et2O (100 mL), washed with water (2×50 mL) and brine (25 mL). The organic layer dried (Na2SO4), filtered and concentrate. The residue was then purified by Biotage (5-30% EtOAc/hexane) to afford (S)-ethyl 2-(tert-butoxy)-2-(7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-2-(hydroxymethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (580 mg, 0.750 mmol, 65.6% yield) as viscous oil. 1H NMR (500 MHz, CDCl3) δ 7.74-7.70 (m, 4H), 7.46-7.35 (m, 6H), 6.48 (s, 1H), 5.90 (br. s., 1H), 4.91-4.83 (m, 2H), 4.29-4.11 (m, 2H), 3.94-3.84 (m, 1H), 3.41-3.29 (m, 3H), 2.61 (s, 3H), 2.17 (q, J=5.8 Hz, 1H), 1.94-1.87 (m, 2H), 1.87 (br. s., 1H), 1.66 (br. s., 1H), 1.59 (s, 3H), 1.58-1.40 (m, 5H), 1.33-1.26 (m, 3H), 1.26-1.21 (m, 12H), 1.09 (d, J=6.1 Hz, 3H), 1.07 (s, 9H). LCMS (M+H)=773.4.

Provenance & Evidence