反应详情

温度

20 °C

A mixture of 2-(6-chloro-1-(phenylsulfonyl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole (1.0 eq., 1 wt, 10.0 g), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (1.1 eq., 0.535 wt, 5.35 g) and K3PO4 (1.2 eq., 0.509 wt, 5.09 g) are charged sequentially to a stirred vessel containing IPA (5 vols, 50 ml) and water (5 vols, 50 ml). KHF2 (2.2 eq., 0.344 wt, 3.44 g) is then added and the mixture heated to 75-80° C. under a flow of N2 for at least 1 hr to degas. Meanwhile, IPA (5 vols, 50 ml) is charged to a separate vessel and heated to reflux for 1 hr under a stream of N2 to degas. The IPA is cooled to 20° C. and Pd(OAc)2 (0.02 eq., 0.0090 wt, 90.0 mg) and tricyclohexylphosphine (0.04 eq., 0.0224 wt, 224 mg) are added sequentially and aged for 1 hr until a yellow solution is observed. The yellow solution is then added over 10 mins to the first vessel maintaining the temperature at 75-80° C. and stirred for at least 4 hours. The mixture is cooled to 20° C. and aged for at least 1 hr. The slurry is then filtered and washed with 1:1 IPA:water (2 vols, 20 ml) followed by water (2×2 vols, 2×20 ml) and dried in vacuo at 60±3° C. to constant temperature to afford 2-(6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole as a yellow solid.

1. additionare charged sequentially to a stirred vessel
2. customto degas
3. additionMeanwhile, IPA (5 vols, 50 ml) is charged to a separate vessel
4. temperatureheated
5. temperatureto reflux for 1 hr under a stream of N2
6. customto degas
7. additionThe yellow solution is then added over 10 mins to the first vessel
8. temperaturemaintaining the temperature at 75-80° C.
9. temperatureThe mixture is cooled to 20° C. and aged for at least 1 hr
10. filtrationThe slurry is then filtered
11. washwashed with 1:1 IPA
12. customdried in vacuo at 60±3° C. to constant temperature