Water → HCID 69522900, Verbindung

Temperatur

100 °C

A mixture of N-(1-carboxyisoquinolin-5-yl)-N′-[4-(trifluoromethyl)benzyl]urea (Example 117, 309 mg, 0.794 mmol), diphenylphosphoryl azide (210 μl, 0.975 mmol) and triethylamine (210 μl, 1.50 mmol) in 1,4-dioxane (25 ml) was heated at 100° C., under a nitrogen atnosphere for 1.5 h. Water (0.25 ml) was then added and the reaction mixture heated for a further 1 hour. The reaction mixture was then cooled to room temperature, filtered and the filtrate evaporated. The residue was purified using a Bond-Elut SCX ion-exchange cartridge, first eluting non-basic materials with methanol, then eluting the product with 2M methanolic ammonia. The basic fractions were evaporated and further purified by flash column chromatography (eluant 5% MeOH-95% dichloromethane increasing to 10% MeOH-90% dichloromethane). The product was then passed through a second SCX purification to give the title compound (77 mg, 27%). m/z (ES+) 361 (M+H)+.

1. temperaturethe reaction mixture heated for a further 1 hour
2. temperatureThe reaction mixture was then cooled to room temperature
3. filtrationfiltered
4. customthe filtrate evaporated
5. customThe residue was purified
6. washfirst eluting non-basic materials with methanol
7. washeluting the product with 2M methanolic ammonia
8. customThe basic fractions were evaporated
9. customfurther purified by flash column chromatography (eluant 5% MeOH-95% dichloromethane increasing to 10% MeOH-90% dichloromethane)
10. customThe product was then passed through a second SCX purification

ORD-Eintrag

ord-b5eb817bb0214665b6ff118dea33e317

Quelldatensatz

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07285563B2