Hydrochloric Acid → Methyl 3-amino-6-(4-(4-methylpiperazin-1-ylsulfonyl)phenyl)pyrazine-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

Triisopropyl borate (2.7 mL, 11.6 mmol) was added to a solution of 1-[(4-bromophenyl)sulfonyl]-4-methylpiperazine in (1.24 g, 3.87 mmol; described: in Keasling, H. H. et el. J. Med. Chem. 1965, 8, 548-550) in anhydrous tetrahydrofuran (25 mL) at −78° C. under an atmosphere of nitrogen, followed by dropwise addition of n-butyllithium (9.8 mL, 15.5 mmol). The resulting mixture was stirred at −78° C. for 30 min, then allowed to warm to room temperature. HCl (3 M aq, 7.8 mL, 23.2 mmol) was added and the mixture was stirred at room temperature for 10 min. Sodium carbonate (4.1 g, 38.7 mmol) was added followed by the addition of methyl 3-amino-6-bromo-2-pyrazinecarboxylate (0.79 g, 3.4 mmol; described in: H. Ellingson, J. Amer. Chem. Soc. 1949, 2798) and Pd(dppf)Cl2 (95 mg, 0.12 mmol). The resulting mixture was heated at 55° C. overnight. Silica was added, the solvent was evaporated and the crude mixture was purified by column chromatography on silica using chloroform/methanol, (99:1), as the eluent to give 0.923 g (69% yield) of the base as a yellow solid: 1HNMR (DMSO-d6) δ 9.0 (s, 1H), 8.22 (d, J=7 Hz, 2H), 7.80 (d, J=7 Hz, 2H), 7.62 (br s, 2H), 3.90 (s, 3H) 2.91 (m, 4H), 2.36 (m, 4H), 2.12 (s, 3H); 13C NMR (DMSO-d6) δ 166.2, 155.1, 145.8, 140.33, 127.5, 134.0, 128.1, 125.7, 109.1, 53.5, 52.3, 45.7, 45.2; MS (ESP) m/z 392 (M++1).

Provenance & Evidence