Diisopropylethylamine → 1-cyclopropyl-3-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide

Participants

Reaction Steps

To a heterogeneous mixture of 1-cyclopropyl-3-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (160.0 mg, 0.37 mmol) and O-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-hydroxylamine (113.1 mg, 0.77 mmol, 2.1 eq) in anhydrous N,N-dimethylformamide (5.7 mL) was added N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (278.3 mg, 0.74 mmol, 2.0 eq) and N,N-diisopropylethylamine (0.25 mL, 1.46 mmol, 4.0 eq), and the resulting homogeneous reaction mixture was stirred under N2 at RT for 16 h. The reaction mixture was quenched with MeOH (2 mL), and the crude material was absorbed onto silica. The crude mixture was purified by flash column chromatography (silica, ISCO, 45 mL/min, 25 to 100% EtOAc in hexane) to afford the product as an orange waxy solid (75.4 mg; 36.4%). LC-MS (method C): [M+H]+=567.2, RT=0.73 min.

Provenance & Evidence