Dimethylformamide → 5-[3,3-Dimethyl-4-(tetrahydro-pyran-2-yloxy)-but-1-ynyl]-3-{(4-methyl-cyclohexanecarbonyl)-[4-(pyridin-2-yloxy)-cyclohexyl]-amino}-thiophene-2-carboxylic acid

Participants

Reaction Steps

A solution of 2-(2,2-dimethyl-but-3-ynyloxy)-tetrahydro-pyran (147 mg, 0.806 mmol), 3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-iodo-thiophene-2-carboxylic acid methyl ester (326 mg, 0.645 mmol) and triethylamine (1.0 mL, 7.17 mmol) in DMF (1.0 mL) was degassed for 10 minutes with nitrogen. PdCl2(PPh3)2 (20 mg, 0.028 mmol) and CuI (5.0 mg, 0.026 mmol) was added and the resulting mixture was degassed with nitrogen for an additional 5 minutes after which the reaction was in a 60° C. oil bath and heated for 4 h. The reaction was cooled and partitioned between ethyl acetate and sat. NaHCO3. The organic layer was separated, washed with 5% LiCl, brine, dried over Na2SO4 and concentrated to give a dark orange-brown foam. Purification by flash column chromatography on silica gel using 20% hexanes in ethyl acetate provided the desired product (251 mg, 69%) as a pale yellow foam.

Provenance & Evidence