Methyl chloroglyoxylate → Methyl 2-(2-(3-chlorophenyl)-7-isobutyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate

Participants

Reaction Steps

To a stirred solution of 6-bromo-7-chloro-2-(3-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidine (0.179 g, 0.5 mmol), copper(I) bromide (0.036 g, 0.250 mmol) and 0.5M LiCl/THF (8 ml, 4.00 mmol) was added 2M i-BuMgCl/THF (2.000 ml, 4.00 mmol) over 5 min at rt. After 2 h, LCMS indicated presence of mostly the unreacted starting material. More iBuMgCl (1 ml) was added and continued stirring at rt for additional 4 h and methyl 2-chloro-2-oxoacetate (0.736 ml, 8.00 mmol) added at once to the reaction mixture, and stirred for additional 1 h. Then, the reaction was diluted with Et2O (50 mL), quenched with Na2CO3 (1 mL), washed with 10 mL each water and brine, dried (Na2SO4), filtered and concentrated to give orange paste which was purified by prep-HPLC to afford methyl 2-(2-(3-chlorophenyl)-7-isobutyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (0.0772 g, 0.170 mmol, 34.0% yield) as yellow oil which turned to yellow solid overtime and contaminated with about 15% of 2-(3-chlorophenyl)-7-isobutyl-5-methylpyrazolo[1,5-a]pyrimidine. 1H NMR (500 MHz, CDCl3) δ: 7.98 (d, J=1.8 Hz, 1H), 7.87-7.83 (m, 1H), 7.41-7.31 (m, 2H), 6.87 (s, 1H), 3.97 (s, 3H), 3.13 (d, J=7.3 Hz, 2H), 2.51 (s, 3H), 2.44 (dt, J=13.7, 6.8 Hz, 1H), 0.97 (d, J=6.7 Hz, 6H). LCMS (M+H) calcd for C20H21ClN3O3: 386.13. found: 386.3.

Provenance & Evidence