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A suspension of compound 2,4-dioxo-1 H-3,1 -benzoxazine-6-sulfonyl chloride (10 g, 38.3 mmol) in DMF (100 mL) was treated with 1 -methylcyclopropanamine hydrochloride (4.1 g, 38.3 mmol) and cooled to -10 °C in an ice/MeOH bath. Triethylamine (8.51 g, 87.5 mmol) was added to the mixture and the resulting solution was stirred at -10 °C for 1 h. (1 -Methyl-1 H-pyrazol-4-yl)methanamine (8.45 g, 57.5 mmol) in DMF (10 mL) was added to the mixture at 0 °C, followed by triethylamine (1 1 .6 g, 1 15 mmol) and the reaction mixture was stirred at room temperature for 3 h. Water (200 mL) was added to the reaction mixture, then extracted with EtOAc (2 chi 100 mL). The combined organic phase was washed with brine (100 mL), dried over sodium sulfate, filtered and evaporated. The crude product was purified by automated column chromatography SiO2 (Biotage, 120 g, eluent: 0-80percent EtOAc in petroleum ether) to give 2-amino-5-[(1 -methylcyclopropyl)sulfamoyl]-N-[(1 - methylpyrazol-4-yl)methyl]benzamide (4.7 g, 12.9 mmol, 34percent).1H NMR (300MHz, DMSO-d6) delta = 8.83 (t, J = 5.7 Hz, 1 H), 7.87 (d, J = 2.3 Hz, 1 H), 7.58 (s, 1 H), 7.55 (s, 1 H), 7.46 (dd, J = 2.2, 8.7 Hz, 1 H), 7.35 (s, 1 H), 7.09 (br. s, 2H), 6.79 (d, J = 8.8 Hz, 1 H), 4.22 (d, J = 5.7 Hz, 2H), 3.78 (s, 3H), 1 .04 (s, 3H), 0.65 - 0.51 (m, 2H), 0.36 - 0.29 (m, 2H),Prepared from 2,4-dioxo-i H-3,i -benzoxazine-6-sulfonyl chloride, 1-methylcyclopropanamine hydrochloride and aminoacetonitrile bisulfate.1H NMR (300MHz, ODd3) O = 7.19 (s, 1H), 7.99 (d, J= 2.2 Hz, 1H), 7.67(dd, J= 2.1, 8.8 Hz, 1H), 7.22 - 7.16 (m, 1H), 6.73 (d, J= 8.8 Hz, 1H), 5.06 (br. s, 1H),4.32 (d, J = 5.7 Hz, 2H), 1 .23 (s, 2H), 0.81 - 0.76 (m, 2H), 0.50 - 0.45 (m, 2H) |