Hydrochloric Acid → HCID 10459419, compound

Participants

Reaction Steps

Triisopropyl borate (0.82 mL, 3.6 mmol) was added to a stirred solution of 1-[(4-bromophenyl)sulfonyl]-4-methylpiperazine (0.38 g, 1.2 mmol; described: in Keasling, H. H. et el. J. Med. Chem. 1965, 8, 549-550) in anhydrous tetrahydrofuran (115 mL) at −78° C. under an atmosphere of nitrogen, followed by dropwise addition of n-butyllithium (2.4 mL, 3.6 mmol) over 10 min. The resulting mixture was allowed to warm up to room temperature and was stirred for another 10 min at ambient temperature. Aqueous HCl (3 M, 1.9 mL, 6.0 mmol) was added and the mixture was stirred for 10 min, followed by an addition of sodium carbonate (1.26 g, 11.9 mmol). 3-Amino-6-bromo-N-(2-thien-2-ylethyl)pyrazine-2-carboxamide (0.272 g, 0.83 mmol) and Pd(dppf)Cl2 (39 mg, 0.05 mmol) were added and the resulting mixture was heated at 65° C. for 1 h. The solvent was evaporated, the resulting residue dissolved in methylene chloride/water, and the aqueous phase was extracted with ethyl acetate. The combined organic phases were evaporated, methanol was added, and the insoluble material was filtered off. The solvent was evaporated and the residue was purified on a silica gel column using methylene chloride/methanol/triethyl amine, (98:2:0.1), as the eluent. The crude product was purified by re-crystallization from methanol to give the free base that was treated with HCl (1.0 M in diethyl ether, 0.6 mmol). The formed precipitate was filtered off and dried under vacuo to give 25 mg (6% yield) of the title compound as a yellow solid: 1H NMR (DMSO-d6, 400 MHz) δ 10.55 (br s, 1H), 9.05 (m, 1H), 8.99 (s, 1H), 8.46 (d, J=8 Hz, 2H), 7.82 (d, J=8 Hz, 2H), 7.37 (d, J=5 Hz, 1H), 6.98 (m, 2H), 3.83 (m, 2H), 3.58 (m, 2H), 3.46 (m, 2H), 3.13 (m, 4H), 2.75 (s, 3H), 2.67 (m, 2H); MS (S) m/z 487 (M++1).

Provenance & Evidence