反应详情

温度

165 °C

Pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [2-bromo-4-(5-chloro-2-difluoromethoxy-phenyl)-thiazol-5-yl]-amide (820 mg, 1.64 mmol) and 1,4 dioxa-8-azaspiro[4.5]decane (1.05 ml, 8.2 mmol) were dissolved in DMA (10 ml) and heated in a microwave at 165° C. for 1 hour. The reaction mixture partitioned between ethyl acetate and water and the phases separated. The organic layer was washed with brine. The combined aqueous layers were extracted with ethyl acetate once and the organic layers combined, dried (Na2SO4), filtered and the solvent removed. The crude product was chromatographed on silica eluting with 50-60% ethyl acetate in cyclohexane. Appropriate fractions were combined and evaporated to afford pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [4-(5-chloro-2-difluoromethoxy-phenyl)-2-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-thiazol-5-yl]-amide as a yellow solid (541 mg, 59%). LCMS (Method 3) [M+H]+=563.3, RT=3.68 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 10.26 (s, 1H), 9.37 (dd, 1H, J=1.6, 6.9 Hz), 8.69 (s, 1H), 8.64 (dd, 1H, J=1.5, 4.4 Hz), 7.68 (d, 1H, J=2.5 Hz), 7.59 (dd, 1H, J=2.7, 8.7 Hz), 7.42 (d, 1H, J=8.5 Hz), 7.31 (dd, 1H, J=4.3, 7.0 Hz), 7.18 (t, 1H, J=73.8 Hz), 3.94 (s, 4H), 3.52 (dd, 4H, J=5.7, 5.7 Hz), 1.75 (dd, 4H, J=5.7, 5.7 Hz).

1. customThe reaction mixture partitioned between ethyl acetate and water
2. customthe phases separated
3. washThe organic layer was washed with brine
4. extractionThe combined aqueous layers were extracted with ethyl acetate once
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. customthe solvent removed
8. customThe crude product was chromatographed on silica eluting with 50-60% ethyl acetate in cyclohexane
9. customevaporated