Dichloromethane → HCID 89526046, compound

Participants

Reaction Steps

To a flask containing tert-butyl 8-((6-(N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)sulfamoyl)-5-fluoro-2-oxobenzo[d]oxazol-3(2H)-yl)methyl)-4,4-difluoro-3,4-dihydroisoquinoline-2(1H)-carboxylate (44-4) (45 mg, 0.060 mmol) (prepared from 43-1 by a sequence analogous to that presented herein) in DCM (3 ml) was added TFA (300 μl, 3.89 mmol). The reaction mixture was then stirred at room temperature. Followed by LC/MS. After 20 minutes the reaction mixture was diluted/quenched with DMSO, then MeOH then filtered (syringe filter) then concentrated (to remove DCM), then diluted with MeOH/DMSO & filtered. The filtrate was purified (without workup) by reverse phase chromatography (5-75% MeCN/H2O; 0.1% TFA in AQ; 20 min gradient; Waters 30×150 mm Sunfire 5 micron C18 column); desired fractions concentrated (GENEVAC), then dissolved in MeOH/DCM & added saturated HCl in EtOAc (˜4N) & concentrated to yield 3-((4,4-difluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)methyl)-5-fluoro-2-oxo-N-(thiazol-2-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide hydrochloride (44-5). HRMS [M+H]: calculated; 497.0560, observed; 497.0556. 1H NMR (499 MHz, DMSO): δ 7.77 (d, J=5.5 Hz, 1H); 7.73 (d, J=7.5 Hz, 1H); 7.58-7.50 (m, 2H); 7.39 (d, J=9.4 Hz, 1H); 7.29 (d, J=4.6 Hz, 1H); 6.88 (d, J=4.6 Hz, 1H); 5.13 (s, 2H); 4.52 (s, 2H); 3.99 (t, J=11.8 Hz, 2H).

Provenance & Evidence