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

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Reaction Conditions

Reaction Steps

Alternatively, 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) (8.2 g, 14.75 mmol) in DMSO (150 mL) and aqueous NaOH (5M) (11.80 mL, 59.0 mmol) was heated at 150° C. for ca. 15 min. Extra aqueous NaOH (5M) (11.80 mL, 59.0 mmol) was added and the mixture heated at 150° C. for another 45′ min. After cooling to RT, the mixture was diluted with water (200 mL) and acidified with formic acid (ca. pH 4-5). The mixture was then extracted with 20% MeOH/DCM (75 mL×5) and the combined organics dried and concentrated. Water (100 mL) was added to the residue and a precipitate crashed-out which was collected by filtration and rinsed with water (50 mL×3). The solid was dried and subsequently taken-up in diphenyl ether (100 mL, 629 mmol) and DMSO (20 mL) and the mixture heated at 200° C. for ca. 35 min. After cooling to RT, the mixture was purified on silica, eluting with a gradient of 0-100% ethyl acetate in cyclohexane followed by 10% MeOH in DCM, to give the title compound (3.03 g).

Provenance & Evidence