Dimethylformamide → HCID 117626358, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of (S)-ethyl 6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-chloro-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (21.4 g, 53.8 mmol), 4-(allyloxy)-4-methylpiperidine, HCl (11.34 g, 59.2 mmol) and DIEA (10.33 ml, 59.2 mmol) in DMF (100 mL) was stirred at 60° C. (oil bath temp) for 22 h. Note: LCMS of the reaction mixture was identical at 2 and 22 h, indicating that there may not be enough amine for the reaction to complete. The amineHCl salt was free flowing liquid, possible due to the absorbtion of lot of water. So, additional amine HCl (7.85 g, 41 mmol) and DIEA (5 mL) were added and continued stirring at 60° C. for 4 h. Then, cooled, diluted with Et2O (300 mL), washed with water (3×50 mL), brine (50 mL), dried (MgSO4), filtered and concentrated to give brown viscous oil. Flash chromatography using 4:1 Hex/EtOAc afforded (S)-ethyl 7-(4-(allyloxy)-4-methylpiperidin-1-yl)-6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (25.9 g, 50.1 mmol, 93% yield) as yellow paste. 1H NMR (400 MHz, CDCl3) δ 7.03 (s, 1H), 6.11-6.01 (m, 1H), 5.86 (br. s., 1H), 5.45 (d, J=17.8 Hz, 1H), 5.22 (dd, J=10.4, 1.6 Hz, 1H), 4.50-4.43 (m, 2H), 4.29-4.18 (m, 2H), 4.06-4.01 (m, 2H), 3.90-3.25 (br. s, 4H), 2.63 (s, 3H), 2.05-1.90 (m, 2H), 1.80-1.69 (m, 1H), 1.66-1.59 (m, 1H), 1.45 (t, J=7.1 Hz, 3H), 1.37 (s, 3H), 1.25-1.21 (m, 12H). LCMS (M+H)=517.5.

Provenance & Evidence