Hydrochloric Acid → HCID 54742800, compound

Participants

Reaction Conditions

Reaction Steps

The starting material, 9-cyclopropyl-6,7-difluoro-3-hydroxyl-8-methoxy-4-oxo-4,9-dihydrothieno[2,3-b]quinoline-2-carboxamide, is prepared from ethyl 1-cyclopropyl-6,7-difluoro-2-mercapto-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate. (See US 2008071086, and Hashimoto, et al., 2007) using a procedure analogous to that describing the preparation of 9-cyclopropyl-6,7-difluoro-3-hydroxyl-4-oxo-4,9-dihydrothieno[2,3-b]quinoline-2-carboxamide. ((Chiba, et al., JP 03-223289) 1H NMR: δ 0.98-1.03 (m, 2H), 1.24-1.31 (m, 2H), 3.86-3.93 (m, 1H), 4.04 (d, J=1.5 Hz, 3H), 7.88 (dd, J=10.0 Hz, 8.5 Hz, 1H). 19F NMR: δ −145.5 (d, J=22.5 Hz, 1F), −139.4 (d, J=22.5 Hz, 1F). LCMS: m/z calcd for C16H12F2N2O4S ([M]+) 366. found ([M+H]+) 367. The title compound is prepared as follows. (R)-2-(Pyrrolidin-3-yl)propan-2-amine (175 mg, 1.4 mmol) is added to a mixture of 9-cyclopropyl-6,7-difluoro-3-hydroxyl-8-methoxy-4-oxo-4,9-dihydrothieno[2,3-b]quinoline-2-carboxamide (100 mg, 0.3 mmol) in pyridine (9 mL). The reaction mixture is heated at 100° C. for 24 h, cooled to rt, and evaporated under reduced pressure. The resulting residue is purified by preparative HPLC using mass-based fraction collection to provide the desired mass only fractions. The fractions containing product were combined and lyophilized. The resulting solid was treated with a solution of 1.25 M HCl in methanol (3 mL), evaporated, and triturated with diethyl ether. This step was repeated three times. The solid was dissolved in water and lyophilized to afford the desired product (40 mg, 29%, HCl salt).

Provenance & Evidence