Formic Acid → 3-chloro-N-[6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]benzenesulfonamide

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Reaction Conditions

Reaction Steps

A mixture of ethyl 4-{[(3-chlorophenyl)sulfonyl]amino}-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridine-5-carboxylate (Description 73) (250 mg, 0.524 mmol) in DMSO (5 mL) and aqueous NaOH (2M) (1.048 mL, 5.24 mmol) was heated at 150° C. for ca. 1 h. After cooling to RT, the mixture was diluted with water (20 mL) and acidified with formic acid (pH ca. 4-5). The mixture was extracted with 10% MeOH in 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 was taken-up in diphenyl ether (2.501 mL, 15.72 mmol) and DMSO (0.5 mL) and the mixture heated at 200° C. for ca. 45 min. After cooling to RT, the mixture was purified by normal phase chromatography, eluting with a gradient of 0-100% ethyl acetate in cyclohexane followed by a gradient of 0-10% MeOH in DCM and then further purified by MDAP (basic conditions), to give the title compound (49 mg). LCMS (A) m/z: 405 [M+1]+, Rt 0.98 min (acidic).

Provenance & Evidence