反应详情

To a flask containing N-(2,4-dimethoxybenzyl)-5-fluoro-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (11-3) (87 mg, 0.187 mmol), resin bound (PS) TRIPHENYLPHOSPHINE (159 mg, 0.350 mmol), tert-butyl 4-fluoro-8-(hydroxymethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (24-7) (89 mg, 0.316 mmol) & DI-TERT-BUTYL AZODICARBOXYLATE (97 mg, 0.421 mmol) was added THF (2 mL). The reaction mixture was then capped (not under N2) & agitated at room temperature. Followed by LC/MS. After ˜10 min at room temp r×n mixture (clear tan & resin), filtered (to remove resin), then concentrated. Purification by silica gel chromatography (0-50%; EtOAc/Hex; 24 g ISCO); desired fractions concentrated, then the resulting residue was repurified by reverse phase chromatography (10-100% MeCN/H2O; 0.1% TFA in AQ; 20 min gradient; Waters 30×150 mm Sunfire 5 micron C18 column); desired fractions free based (suspended in EtOAc, washed with saturated NaHCO3, then H2O, then brine; organics dried over Na2SO4, filtered & concentrated) to yield tert-butyl 8-((6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-5-fluoro-2-oxobenzo[d]oxazol-3(2H)-yl)methyl)-4-fluoro-3,4-dihydroisoquinoline-2(1H)-carboxylate (24-8).

1. customThe reaction mixture was then capped (not under N2) &
2. filtrationfiltered
3. custom(to remove resin)
4. concentrationconcentrated
5. customPurification by silica gel chromatography (0-50%; EtOAc/Hex; 24 g ISCO)
6. concentrationdesired fractions concentrated
7. customthe resulting residue was repurified by reverse phase chromatography (10-100% MeCN/H2O; 0.1% TFA in AQ; 20 min gradient; Waters 30×150 mm Sunfire 5 micron C18 column)
8. washwashed with saturated NaHCO3
9. dry with materialorganics dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated)