Methanesulfonyl chloride → 2-(4-(2,4-difluorobenzyl)piperazin-1-yl)-N-isopropyl-6-(methylsulfonyl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(4-(2,4-difluorobenzyl)piperazin-1-yl)-N-isopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine (50 mg, 0.124 mmol) and DIPEA (0.032 mL, 0.186 mmol) in DCM (1 mL) was added methanesulfonyl chloride (10.6 μL, 0.137 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 1 hr and concentrated via rotary evaporation. The resulting crude material was partitioned between EtOAc (2 mL) and water (1 mL). The organic phase was washed with brine, dried over Na2SO4, filtered, rinsed with EtOAc, and concentrated via rotary evaporation. The crude material was dissolved in EtOAc and MeOH, adsorbed on silica gel (0.75 g), and purified via medium pressure chromatography using a gradient eluant of 50% to 100% EtOAc in heptane on a 4 g silica gel column (Single Step™) to give the title compound (50.6 mg, 85%) as an off-white solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 1.12-1.19 (m, 6H), 2.53-2.61 (m, 4H), 2.74 (t, J=5.9 Hz, 2H), 2.97 (s, 3H), 3.00 (d, J=7.3 Hz, 4H), 3.44-3.48 (m, 1H), 3.59 (s, 2H), 4.02-4.10 (m, 1H), 4.16 (s, 2H), 5.41 (d, J=7.8 Hz, 1H), 7.08 (td, J=8.4, 2.2 Hz, 1H), 7.22 (td, J=9.9, 2.7 Hz, 1H), 7.44-7.54 (m, 1H); ESI-MS m/z [M+H]+ 480.9.

Provenance & Evidence