Hydrochloric Acid → HCID 178428863, compound

Participants

Reaction Steps

A solution of [6-(6-cyano-pyrazin-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester (200 mg, 0.57 mmol) in methanol (4.7 mL) was bubbled through gaseous HCl for 40 minutes at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 4 h. The solvent was removed under reduced pressure. To the residue was added methanol (2.5 mL) and ammonia solution (28%, 0.27 mL). The reaction mixture was refluxed for overnight. LC-MS showed all material converted to methyl imidate while the ethyl ester group was also hydrolyzed to free acid. The solvent was removed under reduced pressure. Half of the residue (0.28 mmol) was dissolved in methanol (2 mL) and isobutylamine (0.29 mL, 2.9 mmol) was added. The reaction mixture was refluxed overnight. The pH was adjusted to pH 3 with aqueous HCl (6 N). Prep-HPLC separation (C18 column) gave the title compound (11 mg, 10%) as a white solid. 1H NMR (300 MHz, CD3OD) δ 8.90 (1H, s), 8.58 (1H, s), 7.25 (1H, s), 7.14 (1H, s), 5.65 (1H, dd), 3.15 (1H, m), 3.02 (2H, m), 2.60 (3H, s), 2.30 (1H, m), 1.78 (1H, m), 0.95 (3H, d), 0.94 (3H, d). MS found (electrospray): (M+H)+=399.2.

Provenance & Evidence