Sodium Carbonate → (S,E)-Ethyl 6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-5-methyl-7-(4-methylpent-1-en-1-yl)pyrazolo[1,5-a]pyrimidine-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of (S)-ethyl 6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (300 mg, 0.613 mmol), (E)-(4-methylpent-1-en-1-yl)boronic acid (94 mg, 0.736 mmol) and 2N Na2CO3 (0.613 mL, 1.226 mmol) in DMF (6 mL) was degassed for 15 min. Tetrakis(triphenylphosphine)palladium(0) (49.6 mg, 0.043 mmol) was then added and the degassing was continued for another 5 min. The mixture was then heated at 100° C. for 2 h. At this point LCMS indicated completion of reaction and presence of desired product. After cooling to room temperature, water was added (10 mL) and the mixture was extracted with ether (2×50 mL), washed with brine (25 mL), dried (Na2SO4), filtered and concentrated. the crude was then purified by biotage (5-30% EtOAc/hexane) to afford (S,E)-ethyl 6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-5-methyl-7-(4-methylpent-1-en-1-yl)pyrazolo[1,5-a]pyrimidine-2-carboxylate (200 mg, 0.449 mmol, 73.2% yield) as off-white solid. 1H NMR (500 MHz, CDCl3) δ 7.09 (s, 1H), 7.07 (s, 0.6H), 7.04 (s, 1H), 5.57 (s, 1H), 4.49 (q, J=7.1 Hz, 2H), 4.33-4.20 (m, 2H), 2.70 (s, 3H), 2.40 (td, J=7.0, 1.3 Hz, 2H), 1.90 (dt, J=13.4, 6.7 Hz, 1H), 1.46 (t, J=7.1 Hz, 3H), 1.29 (t, J=7.1 Hz, 3H), 1.17 (s, 9H), 1.06 (dd, J=6.6, 2.7 Hz, 6H). LCMS (M+H)=446.4.

Provenance & Evidence