Sodium Hydroxide → 3-(4-Bromo-2-fluoro-phenylamino)-thieno[2,3-c]pyridine-2-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide

Participants

Reaction Conditions

Reaction Steps

A mixture of ethyl 3-(4-bromo-2-fluoro-phenylamino)-thieno[2,3-c]pyridine-2-carboxylate (63 mg, 0.16 mmol), 1N aqueous NaOH solution (0.17 ml, 0.17 mmol) and ethanol (2 ml) was heated at 65° C. for 45 minutes. The resultant reaction mixture was concentrated in vacuo then the residue was azeotroped with toluene (2×2 ml) to give a solid residue. The resultant solid residue was suspended in anhydrous THF (2 ml) before O—((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)hydroxylamine (38 mg, 0.32 mmol), EDCI (38 mg, 0.20 mmol), HOBt (30 mg, 0.22 mmol) and DIPEA (83 μl. 0.48 mmol) were added. After stirring for 66 hours at ambient temperature, the reaction mixture was concentrated in vacuo to afford a yellow residue. The resultant residue was dissolved in ethyl acetate (50 ml) and washed with water (20 ml), before the organic layer was isolated, dried over sodium sulfate, then concentrated in vacuo to afford a yellow oil. The oil was purified by flash chromatography (Si-SPE, pentane:ethyl acetate, gradient 60:40 to 0:100) to afford the title compound as a yellow foam (61 mg, 77%). LCMS (method B): RT=3.02 min, M+H+=496/498.

Provenance & Evidence