Formic Acid → 3-chloro-N-[3,6-dimethyl-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}-3,6-dimethyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridine-5-carboxylate (Description 64) (150 mg, 0.306 mmol) in DMSO (5 mL) and aqueous NaOH (2M) (0.611 mL, 3.06 mmol) was heated at 150° C. for ca. 1.5 h. After cooling to RT, the mixture was diluted with water (20 mL), acidified with formic acid (ca. pH 4-5) and extracted with 10% MeOH in DCM (30 mL×5). The combined organics were dried and concentrated. The residue was passed through a C18 solid phase extractor cartridge, eluting with water (30 mL×4) and then with MeOH (30 mL×4) and the combined organics concentrated. The residue was taken-up in diphenyl ether (2 mL, 12.57 mmol) and DMSO (0.5 mL) and the mixture was 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 and then with 0-20% MeOH in DCM and then further purified by MDAP (acidic conditions), to give the title compound (12 mg). LCMS (A) m/z: 419 [M+1]+, Rt 1.04 min (acidic).

Provenance & Evidence