Hydrochloric Acid → N-[2-({1-[6-(methyloxy)-1,5-naphthyridin-4-yl]-3-pyrrolidinyl}thio)ethyl]-3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-sulfonamide

Participants

Reaction Conditions

Reaction Steps

To the solution of HCl salt of [2-({1-[6-(methyloxy)-1,5-naphthyridin-4-yl]-3-pyrrolidinyl}thio)ethyl]amine (from Example 7b) (420 mg, 1.23 mmol) in DCM/MeOH (15 mL, 1:1) with triethylamine (0.86 mL, 6.1 mmol) was added 3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-sulfonyl chloride (388 mg, 1.48 mmol). After stirring at 25° C. for 12 h, the reaction mixture was diluted with chloroform and poured into saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with chloroform, and the combined organic layers were washed with brine, dried over magnesium sulfate, concentrated and purified by column chromatography (silica, 0-10% MeOH in CDCl3 (1% NH4OH) to afford the title compound as a white solid (400 mg, 61%): LC/MS m/z 532 (M+H)+; 1H NMR (CDCl3, 400 MHz) δ 9.05. (br, 1H), 8.34 (d, J=5.8 Hz, 1H), 8.23 (d, J=9.0 Hz, 1H), 7.57 (s, 1H), 7.55 (d, J=7.4 Hz, 1H), 7.48 (d, J=8.1 Hz, 1H), 7.07 (d, J=9.0 Hz, 1H), 6.45 (d, J=5.9 Hz, 1H), 6.2 (br, 1H), 4.38-4.43 (m, 1H), 3.93-4.18 (m, 6H), 3.52-3.61 (m, 1H), 3.47 (s, 2H), 3.22-3.28 (m, 2H), 2.82-02.87 (m, 2H), 2.4-2.47 (m, 1H), 1.99-2.08 (m, 1H).

Provenance & Evidence