2,2-Difluoroethanamine → 6-benzyl-N-(2,2-difluoroethyl)-2-(4-(2,4-difluorophenoxy)piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine

Participants

Reaction Conditions

Reaction Steps

A solution of 6-benzyl-3-chloro-2-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazine (261.1 mg, 0.554 mmol) and 2,2-difluoroethanamine (156 μL, 2.22 mmol) in toluene (1.85 mL) was treated with sodium tert-butoxide (107 mg, 1.11 mmol), BINAP (69.0 mg, 0.111 mmol), and Pd2(dba)3 (50.8 mg, 0.055 mmol). Nitrogen gas (balloon) was bubbled through the reaction mixture for 5 min. The reaction mixture was sealed and stirred at 90° C. overnight. The reaction mixture was allowed to cool to room temperature and was opened to air, and the solution was concentrated under reduced pressure. The residue was taken up in MeOH, filtered, and purified by HPLC Method B using a 35% to 60% ACN gradient to give the title compound, as a TFA salt, as a yellow oil (181.2 mg, 51.9%). ESI-MS m/z [M+H]+ 516.4.

Provenance & Evidence