反应详情

温度

150 °C

A mixture of ethyl 3-bromo-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridine-5-carboxylate (Description 74) (920 mg, 1.65 mmol) in DMSO (15 mL) and aqueous NaOH (5M) (3.31 mL, 16.55 mmol) was heated at 150° C. for ca. 1.5 h. After cooling to RT, the mixture was diluted with water (20 mL) and acidified with formic acid (ca. pH 4-5). The mixture was extracted with 10% MeOH/DCM (30 mL×5) and the combined organics dried and concentrated. The residue was passed through a C18 solid phase extractor cartridge, eluting with water (100 mL×4) and then with MeOH (100 mL×4) and the combined organics concentrated. The residue (877 mg) was taken-up in diphenyl ether (5.0 mL, 31.4 mmol) and DMSO (0.5 mL) and the mixture heated at 200° C. for ca. 1 h. After cooling to RT, the mixture was purified by chromatography on silica, eluting with a gradient of 0-100% ethyl acetate in cyclohexane, to give the title compound (430 mg). LCMS (A) m/z: 483/485 [M+1]+, Rt 1.16 min (acidic).

1. temperatureAfter cooling to RT
2. extractionThe mixture was extracted with 10% MeOH/DCM (30 mL×5)
3. customthe combined organics dried
4. concentrationconcentrated
5. washeluting with water (100 mL×4)
6. temperatureAfter cooling to RT
7. customthe mixture was purified by chromatography on silica
8. washeluting with a gradient of 0-100% ethyl acetate in cyclohexane