反应详情

To a stirred solution of {3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}amine (200 mg, 0.62 mmol) and TEA (64 mg, 0.63 mmol) in THF (25 mL) was added dropwise 2-thiopheneacetyl chloride (118 mg, 0.73 mmol). After stirring for 20 min., 15 min. LC/MS analysis indicated the reaction was complete and several equivalents of PS-trisamine were added and the mixture was stirred for 16 h followed by addition of 25 mg of TEA. The mixture was then filtered and the resin washed well with THF. The filtrate was concentrated and the crude partitioned between water and DCM. The layers were separated, and the aqueous was extracted with DCM. The organics were combined, filtered over MgSO4, filtered, reduced in vacuo to yield the title compound (270 mg, 98% yield). 1H NMR (400 MHz, d6-DMSO) δ 10.41 (s, 1H), 8.92 (d, J=6.9 Hz, 1H), 8.48 (d, J=5.3 Hz, 1H), 8.43 (d, J=9.0 Hz, 1H), 7.91 (s, 1H), 7.78 (d, J=8.1 Hz, 1H), 7.67 (t, J=7.3 Hz, 1H), 7.49 (t, J=7.9 Hz, 1H), 7.40-7.43 (m, 1H), 7.31 (d, J=6.8 Hz, 1H), 7.24 (dt, J=1.1, 6.8 Hz, 1H), 7.07 (d, J=55 Hz, 1H), 6.99-7.01 (m, 2H), 3.91 (s, 2H) ppm. ES-LC/MS m/z=446, 448 [M+H]+.

1. stirringthe mixture was stirred for 16 h
2. filtrationThe mixture was then filtered
3. washthe resin washed well with THF
4. concentrationThe filtrate was concentrated
5. customthe crude partitioned between water and DCM
6. customThe layers were separated
7. extractionthe aqueous was extracted with DCM
8. filtrationfiltered over MgSO4
9. filtrationfiltered