Triethylamine → N-[2-({1-[6-(methyloxy)-1,5-naphthyridin-4-yl]-3-pyrrolidinyl}thio)ethyl]-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxamide

Beteiligte Stoffe

Reaktionsschritte

The hydrochloride salt of [2-({1-[6-(methyloxy)-1,5-naphthyridin-4-yl]-3-pyrrolidinyl}thio)ethyl]amine (from Example 7b) (300 mg, 0.88 mmol) was dissolved in DCM (5 mL) with triethylamine (0.31 mL, 2.2 mmol) and cooled in an ice bath. The cooled solution was treated with ethyl chloroformate (0.15 mL, 1.59 mmol) and triethyl amine (0.79 mL, 5.3 mmol) and stirred for 1 h. 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxylic acid (222 mg, 1.06 mmol) was added. 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 (170 mg, 39%): LC/MS m/z 497 (M+H)+; 1H NMR (CDCl3, 400 MHz) δ 8.33 (d, J=4.4 Hz, 1H), 8.29 (br, 1H), 8.2 (d, J=9.0 Hz, 1H), 8.02-8.06 (m, 1H), 7.88 (d, J=7.8 Hz, 1H), 7.81 (d, J=7.8 Hz, 1H), 7.09 (d, J=9.0 Hz, 1H), 6.47 (d, J=4.4 Hz, 1H), 4.47-4.49 (m, 1H), 3.95-4.15 (m, 6H), 3.75-3.81 (m, 2H), 3.64-3.70 (m, 2H), 3.13-3.17 (m, 1H), 2.92-2.94 (m, 2H), 2.47-2.52 (m, 1H), 2.11-2.19 (m, 1H).

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