Hydrochloric Acid → HCID 56927258, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 7-chloro-2-methyl-3-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-5-(4-morpholinyl)pyrazolo[1,5-a]pyrimidine (2.82 g, 6.64 mmol), prepared using the same procedure used to prepare Example 10, in N,N-Dimethylformamide (50 mL) and methanol (34.1 mL, 843 mmol) was added palladium(II) acetate (0.224 g, 0.996 mmol), DPPF (0.552 g, 0.996 mmol). The reaction mixture was purged with carbon monoxide for 5 min and then TEA (2.78 mL, 19.91 mmol) was added in. The reaction mixture was stirred at 70° C. under CO atmosphere for 6 h. Additional palladium(II) acetate (0.224 g, 0.996 mmol) and DPPF (0.552 g, 0.996 mmol) was added in. The reaction mixture was purged with carbon monoxide for 5 min and then TEA (2.78 mL, 19.91 mmol) was added in. The reaction mixture was stirred at 70° C. under CO atmosphere for 16 h. The reaction was filtered through Celite, and the filtrate was concentrated. The residue was dissolved in Tetrahydrofuran (THF) (100 mL). To the solution of residue in THF was added sodium hydroxide (5.31 mL, 26.6 mmol). The reaction mixture was stirred at rt for 2 h. Water (50 mL) was added in. The reaction was acidified with 5 N HCl, then extracted with DCM (500 mL×3), dried and concentrated. The crude was purified on a silica column (EtOAc/Hexane: 20˜60%) to give the product (1.6 g, 53%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.23 (s, 3H) 2.44 (s, 3H) 3.50-3.62 (m, 4H) 3.62-3.71 (m, 4H) 3.97 (s, 2H) 6.98 (s, 1H) 7.22-7.33 (m, 1H) 7.38 (d, J=7.58 Hz, 1H) 7.52 (d, 1H), 14.60 (b.s., 1H); LC/MS: MS (ES+) m/e 435.4 [M+H]+.

Provenance & Evidence