反应详情

温度

50 °C

IPA (225.0 mL) is added to compound N-{4-chloro-5-[8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazin-3-yl]-thiazol-2-yl}-morpholine (18.8 g, 0.0448 mmol, below) in a 1 L 1-neck round-bottomed flask The starting material slurry is heated to 50° C. on a Buchi bath, at which time a hazy solution resulted. Concentrated (12 M) aqueous HCl (3.73 mL, 0.0448 mmole, 1.0 eq) is added all at once, and the hazy solution is stirred at 50° C. on the Buchi for 10 minutes, then evaporated to a yellow solid under vacuum. After 20 minutes at room temperature under vacuum (weight of 20.9 g), acetone (100 mL) is added and the resulting yellow slurry is stirred at room temperature for 1 hour, then cooled with an ice bath and stirred for an additional 1 hour. The slurry is filtered, rinsed with acetone, and dried overnight under vacuum at 40° C. to provide pale yellow-white crystalline solid 19.18 g (94%). 1H NMR (DMSO): δ 7.52 (s, 1H), 3.73 (t, J=4.6, 4H), 3.49 (t, J=5.2 Hz, 4H), 3.39 (m, 1H), 2.57 (s, 3H), 2.49 (s, 3H), 1.77 (m, 4H), 0.80 (t, J=7.4 Hz, 6H).

1. customresulted
2. additionis added all at once, and the hazy solution
3. customevaporated to a yellow solid under vacuum
4. additionAfter 20 minutes at room temperature under vacuum (weight of 20.9 g), acetone (100 mL) is added
5. stirringthe resulting yellow slurry is stirred at room temperature for 1 hour
6. temperaturecooled with an ice bath
7. stirringstirred for an additional 1 hour
8. filtrationThe slurry is filtered
9. washrinsed with acetone
10. customdried overnight under vacuum at 40° C.