反应详情

温度

50 °C

DMSO (7 vols, 70 ml) and isopropylpiperazine (1.5 eq, 0.387 wt, 0.431 vol, 4.31 ml, 3.87 g) are charged to a clean vessel. 5-(Bromomethyl)-2-(6-chloro-1-(phenylsulfonyl)-1H-indazol-4-yl)oxazole (1.0 eq, 10 g (9.13 g corrected for assay), 1 wt) is added in 5 portions at 20° C. over 1 hr and the mixture stirred for 1 hr. The mixture is heated to 50° C. and aged for 1 hr, then checked for consumption of starting material by HPLC. Diethylamide (1.2 eq, 0.244 wt, 0.336 vol, 2.44 g, 3.36 ml) is added over 10 mins and the mixture aged for 30 mins, then cooled to 20° C. over 1 hr and further aged for 2 hrs. The thick slurry is filtered and washed with DMSO (2×1.5 vols, 2×15 ml) followed by acetone:water 1:2 (3×2 vols, 3×20 ml). The resultant solid is blown dry on the filter and dried at 60° C. in vacuo to constant weight/temperature to afford 2-(6-chloro-1-(phenylsulfonyl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole as an off-white solid.

1. customchecked for consumption of starting material by HPLC
2. waitthe mixture aged for 30 mins
3. temperaturecooled to 20° C. over 1 hr
4. waitfurther aged for 2 hrs
5. filtrationThe thick slurry is filtered
6. washwashed with DMSO (2×1.5 vols, 2×15 ml)
7. customThe resultant solid is blown dry on the
8. filtrationfilter
9. customdried at 60° C. in vacuo to constant weight/temperature