Acetonitrile → Methyl 3-amino-6-[4-[(1-tert-butoxycarbonyl-3-piperidyl)sulfonyl]phenyl]pyrazine-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

tert-butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]sulfonylpiperidine-1-carboxylate (2 g, 4.431 mmol), methyl 3-amino-6-bromo-pyrazine-2-carboxylate (934.6 mg, 4.028 mmol) and K3PO4 (1.710 g, 8.056 mmol) with MeCN (14.09 mL)/water (3.133 mL). Degassed with vacuum/nitrogen over 5 cycles, treated with Pd[P(tBu)3]2 (114.9 mg, 0.2248 mmol), degassed further 5 cycles and stirred under nitrogen for 2 hours at 60° C. The reaction mixture was cooled to ambient temperature and poured onto icewater/ethylacetate. The organic layer was washed with aq NaHCO3, brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel eluting with 50-70% EtAc/petrol. The relevant fractions were concentrated in vacuo to a solid. Trituration with ether/petroleumether gave methyl 3-amino-6-[4-[(1-tert-butoxycarbonyl-3-piperidyl)sulfonyl]phenyl]pyrazine-2-carboxylate as a colourless solid (1.728 g, 3.626 mmol, 90.02%). H NMR (400.0 MHz, DMSO-d6) δ 9.05 (s, 1H), 8.3 (d, 2H), 8.0 (d, 2H), 7.7 (br s, 2H), 4.0-4.1 (m, 1H), 3.9 (s, 3H), 3.7-3.8 (m, 1H), 3.3-3.4 (m, 1H), 2.77-2.95 (m, 2H), 1.95-2.05 (m, 1H), 1.7-1.75 (m, 1H), 1.6-1.65 (m, 1H) and 1.20-1.40 (m, 10H) ppm; LC/MS m/z 421.1 [M−56+1]+.

Provenance & Evidence