Hydrochloric Acid → 1-[(Cyclopropylmethyl)amino]-4-hydroxy-3-{7-[(methoxymethoxy)methyl]-1,1-dioxido-4h-thieno[2,3-e][1,2,4]thiadiazin-3-yl}quinolin-2(1h)-one

Participants

Reaction Conditions

Reaction Steps

The product of Example 350F (78.9 mg, 0.16 mmol) in tetrahydrofuran (4 mL) and methanol (0.013 mL, 0.32 mmol) at 0° C. was treated dropwise with a 2.0 M solution of lithium borohydride in tetrahydrofuran (0.131 mL, 0.24 mmol). The reaction was stirred at 25° C. for 1 hour, acidified with 1N hydrochloric acid to approximately pH 2-4, diluted with water (20 mL), and the resulting precipitate was collected by filtration and dried. The crude product was chromatographed on silica gel with 2% methanol/dichloromethane to give the title compound (41.6 mg, 52.5%). The sodium salt of the title compound was prepared according to the procedure of Example 1D. 1H NMR (300 MHz, DMSO-d6) δ 0.15 (d, J=4.41 Hz, 2 H), 0.42 (d, J=8.09 Hz, 2 H), 1.01 (m, 1 H), 2.84 (d, J=6.62 Hz, 2 H), 4.64 (s, 2 H), 4.71 (s, 2 H), 6.36 (br.s, 1 H), 7.41 (m, 2 H), 7.88 (t, J=7.35 Hz, 1 H), 8.07 (d, J=8.46 Hz, 1 H), 8.16 (d, J=8.09 Hz, 1 H). MS (ESI−) m/z 489 (M−H)−.

Provenance & Evidence