反应详情

A 100 mL RB-flask was charged with 6-bromo-7-chloro-2-(3-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidine (0.918 g, 2.57 mmol) and copper(I) bromide (0.092 g, 0.643 mmol) was added anhydrous THF (30 mL). To the resulting mixture was added 1M iPrMgCl—LiCl/THF (3.34 ml, 3.34 mmol) over 5 min. After 1 h, methyl 2-chloro-2-oxoacetate (0.501 ml, 5.45 mmol) was added at once to the dark reaction mixture and stirred for additional 1 h. Then, the resulting homogeneous orange brown reaction mixture was quenched with sat NaHCO3 (1 mL), diluted with Et2O (75 mL), washed with water (2×25 mL), brine (25 mL), dried (Na2SO4/C), filtered and concentrated to give yellow residue. This residue was purified on silica gel column using 5-30% EtOAc/Hex (5% increment per 500 mL) to give methyl 2-(2-(3-chlorophenyl)-7-isopropyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (0.1402 g, 0.377 mmol, 14.67% yield) as yellow solid; 1H NMR (500 MHz, CDCl3) δ: 8.01-7.98 (m, 1H), 7.87 (dt, J=7.0, 1.7 Hz, 1H), 7.43-7.38 (m, 2H), 6.87 (s, 1H), 3.98 (s, 3H), 3.43-3.34 (m, 1H), 2.47 (s, 3H), 1.62 (d, J=7.0 Hz, 6H). LCMS (M+H) calcd for C17H16N3O2: 372.11. found: 372.2.

1. customonce to the dark reaction mixture
2. customThen, the resulting homogeneous orange brown reaction mixture was quenched with sat NaHCO3 (1 mL)
3. additiondiluted with Et2O (75 mL)
4. washwashed with water (2×25 mL), brine (25 mL)
5. dry with materialdried (Na2SO4/C)
6. filtrationfiltered
7. concentrationconcentrated
8. customto give yellow residue
9. customThis residue was purified on silica gel column