Dimethylformamide → HCID 86687518, compound

Participants

Reaction Conditions

Reaction Steps

A microwave vial was charged with 1-chloro-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (Intermediate OOO; 0.050 g, 0.105 mmol), Pd(Ph3P)4 (0.012 g, 10.50 μmol), and DMF (0.525 ml). 1-Methyl-2-(tributylstannyl)-1H-pyrrole (0.078 ml, 0.210 mmol) was added and the reaction was heated in a microwave reactor at 90° C. for 30 minutes. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via silica gel column chromatography (12 g, gradient elution 0 to 100% EtOAc:Heptane with a 10% MeOH/DCM flush) to afford N-(2,4-dimethoxybenzyl)-1-(1-methyl-1H-imidazol-2-yl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as an off-white solid. m/z (ESI) 522.2 (M+H)+. The material was dissolved in DCM and TFA (8.09 μl, 0.105 mmol) was added. The reaction was stirred for 30 minutes at room temperature. The reaction was concentrated, triturated with diethyl ether, and filtered. The solids were washed with diethyl ether and the filtrate was concentrated and purified via column chromatography (12 g silica gel column, gradient elution 0 to 10% MeOH:EtOAc) to afford 1-(1-methyl-1H-pyrrol-2-yl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=12.93 (br. s., 1H), 9.12 (s, 1H), 8.81 (d, J=5.7 Hz, 1H), 8.64 (s, 1H), 8.34 (d, J=9.0 Hz, 1H), 8.26 (d, J=5.6 Hz, 1H), 8.10 (s, 1H), 8.00 (dd, J=1.9, 8.9 Hz, 1H), 7.30 (d, J=4.5 Hz, 1H), 6.89 (d, J=4.5 Hz, 1H), 3.88 (s, 3H). m/z (ESI) 371.1 (M+H)+.

Provenance & Evidence