反应详情

温度

50 °C

A mixture of 6-chloro-3-fluoro-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (1.3 g, 5.3 mmol), 1-methylcyclobutylamine hydrochloride (1.0 g, 8.1 mmol) and triethylamine (2.5 ml, 18.1 mmol) in ethanol (10 ml) was stirred for 16 h at 50° C. and then for 5 h at 70° C. in a sealed flask. The cooled mixture was concentrated in vacuo and the residue was triturated with water (25 ml) followed by adjustment to pH <2 with 1M hydrochloric acid. The crude product was isolated by filtration, recrystallised from acetic acid and finally purified by chromatography (C18; 20-60% acetonitrile+0.01% TFA) to give 363 mg (22%) of the title compound; mp 294-296° C.; 1H-NMR (DMSO-d6): δ1.48 (s, 3H), 1.75-1.88 (m, 2H), 1.94-2.05 (m, 2H), 2.18-2.31 (m, 2H), 7.08 (s, 1H) 7.33 (br s, 1H), 10.67 (br s, 1H); LC-MS: m/e 306/308 (M+1)+.

1. waitfor 5 h at 70° C. in a sealed flask
2. concentrationThe cooled mixture was concentrated in vacuo
3. customthe residue was triturated with water (25 ml)
4. customThe crude product was isolated by filtration
5. customrecrystallised from acetic acid
6. customfinally purified by chromatography (C18; 20-60% acetonitrile+0.01% TFA)