Triethylamine → HCID 25117148, compound

Participants

Reaction Conditions

Reaction Steps

The preparation of 7-iodo-N,6-dimethylbenzo[d]isoxazol-3-amine was disclosed in PCT Int. Appl. WO 2006094187 A2. A mixture of 7-iodo-N,6-dimethylbenzo[d]isoxazol-3-amine (250 mg, 0.87 mmol) followed by 2-(dicyclohexylphosphino)-2′-methylbiphenyl (63 mg, 0.17 mmol), Pd(OAc)2 (10 mg, 0.043 mmol) in 2.0 mL dioxane in a glass tube was treated with 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.6 mL of 1.0 M in THF solution, 2.6 mmol) and Et3N (0.48 mL, 3.47 mmol) under argon. The glass tube was sealed and the reaction mixture was then heated in a microwave at 100° C. for 20 min. The reaction mixture was cooled to RT and transferred to a 20 mL of RBF, rinsing with 2 mL of THF. To the reaction mixture was added tetrakis(triphenylphosphine)palladium(0) (11.2 mg, 9.67 μmol), 5-bromo-1-(2,4-difluorophenyl)-7-methyl-1H-pyrazolo[4,3-b]pyrazin-6(7H)-one (110 mg, 0.32 mmol; made in a manner similar to the method described in Example 1, Steps 1-3). It was cooled to 0° C. with an ice bath, and sodium carbonate (1.1 mL of 1.0 N solution) was added drop wise. The reaction mixture was stirred at RT for 5 min, and heated in an oil bath at 70° C. for 5 h. The reaction mixture was treated with water and extracted with EtOAc (2×20 mL). The combine EtOAc layers were washed with brine and dried over MgSO4, filtered and concentrated. Purification on the ISCO (12 g column, 25-90% EtOAc in hexanes) afforded 1-(2,4-difluorophenyl)-7-methyl-5-(6-methyl-3-(methylamino)benzo[d]isoxazol-7-yl)-1H-pyrazolo[4,3-b]pyrazin-6(7H)-one as a light yellow amorphous solid. MS (ES+): 423.1 (M+H)+.

Provenance & Evidence