反应详情

A solution of 2-amino-6-cyclopropylbenzonitrile (Example 92a) (1.0 eq., 626 μmol, 99 mg) and sulfamoyl chloride (1.5 eq., 939 μmol, 109 mg) in DMA (1 mL) was stirred in a scintillation vial at room temperature. After 2 hours, NaOH (1.5 eq., 939 μmol, 1N, 939 μL) and water (18 mL) were added and the resulting precipitated product stirred overnight at room temperature. The precipitate was filtered off and washed with water (3×5 mL). The wet precipitate was dissolved in EtOH (5 mL, 200 proof) and NaOH (2.5 eq., 1565 μmol, 1N, 1565 μL) was added. The reaction was heated to 80° C. with stirring overnight. The reaction mixture was cooled to room temperature and HCl (2.5 eq., 1565 μmol, 1N, 1565 μL) was added to the reaction vial. The ethanol and most of the water was removed on the rotary evaporator. The resulting precipitate was suspended in water (5 mL), stirred, filtered off, and washed with water (20 mL). The product was dried in a vacuum oven to give 5-cyclopropyl-1H-benzo[c][1,2,6]thiadiazin-4-amine-2,2-dioxide (41 mg, 28%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 0.71 (m, 2H), 1.04 (m, 2H), 2.401 (m, 1H), 6.85 (d, J=8 Hz, 2H), 7.37 (t+br. s, J=8 Hz, 2H), 8.40 (br. s, 1H), 10.80 (s, 1H). 1H NMR (400 MHz, CD3OD) δ 0.89 (m, 2H), 1.15 (m, 2H), 2.36 (m, 1H), 6.90 (d, J=8 Hz, 1H), 6.97 (d, J=8 Hz, 1H), 7.41 (t, J=8 Hz, 1H). MS 238 (MH+).

1. customthe resulting precipitated product
2. filtrationThe precipitate was filtered off
3. washwashed with water (3×5 mL)
4. dissolutionThe wet precipitate was dissolved in EtOH (5 mL, 200 proof)
5. temperatureThe reaction was heated to 80° C.
6. stirringwith stirring overnight
7. temperatureThe reaction mixture was cooled to room temperature
8. customThe ethanol and most of the water was removed on the rotary evaporator
9. stirringstirred
10. filtrationfiltered off
11. washwashed with water (20 mL)
12. customThe product was dried in a vacuum oven