N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amine → HCID 86687470, compound

Participants

Reaction Conditions

Reaction Steps

To a flask charged with N-(4-methoxybenzyl)thiazol-2-amine (180 mg, 0.816 mmol) was added THF (3 ml) and the resulting mixture cooled in an ice water bath prior to the addition of lithium bis(trimethylsilyl)amide (1M in THF) (855 μl, 0.855 mmol). The resulting light brown solution was stirred for 15 min at 0° C. prior to the addition of a solution of perfluorophenyl 4-bromoisoquinoline-7-sulfonate (353 mg, 0.777 mmol) in THF (2 ml), followed by 1 ml THF wash. The resulting solution was allowed to stir and warm slowly to room temperature (ice melt). After 2 hr LC/MS indicated about 70% conversion fairly cleanly, with starting amine and PFP ester present (no change from 1 hr). The solution was cooled back to 0° C. and 0.5 eq LiHMDS (1 M) was added. After 1 hr LC/MS indicated complete consumption of starting material. To the mixture was added 400 μl acetic acid and the mixture was dried under reduced pressure and purified with a 40 g HP Silicycle column (SiliCycle, Inc. Quebec City, Canada) ramping EtOAc in heptane (0 to 50%, 10% DCM throughout) affording product as a white solid 4-bromo-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-7-sulfonamide (Intermediate PPPP) (202 mg, 0.412 mmol, 53.0% yield). m/z (ESI) 490.0 (M+H)+.

Provenance & Evidence