2-Methylpropan-2-olate → N-(4-(Dipropylphosphoryl)phenyl)-2-iodo-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Temperatur

-10 °C

Patasium tert-Butoxide (0.19 g, 1.65 mmol) was suspended in 4.5 mL anhydrous THF under nitrogen and cooled to −10° C. in an ice-salt bath. 4-(Dipropylphosphoryl)benzenamine (0.12 g, 0.55 mmol) was added to the suspension and the mixture was stirred at −10° C. for 30 min. 6-Chloro-2-iodo-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (Tetrahedron 2002, 58, 7911-7923, 0.18 mg, 0.5 mmol) was then added to the reaction mixture and the content was warmed to room temperature and stirred over night. The reaction mixture was cooled to 0° C., and quenched by the addition of 0.1N HCl (˜500 mL). The mixture was concentrated on a rotavapor. The residue was partitioned between ethyl acetate (10 mL)/water (4 mL), organic layer was separated and washed with 0.1N HCl (4×4 mL), saturated NaHCO3 (4 mL), brine (4 mL), and dried over Na2SO4. The final product was obtained by flash column chromatography on silica gel (7.5% MeOH/DCM).

1. temperaturethe content was warmed to room temperature
2. stirringstirred over night
3. temperatureThe reaction mixture was cooled to 0° C.
4. customquenched by the addition of 0.1N HCl (˜500 mL)
5. concentrationThe mixture was concentrated on a rotavapor
6. customThe residue was partitioned between ethyl acetate (10 mL)/water (4 mL), organic layer
7. customwas separated
8. washwashed with 0.1N HCl (4×4 mL), saturated NaHCO3 (4 mL), brine (4 mL)
9. dry with materialdried over Na2SO4

ORD-Eintrag

ord-1f5cf1783a2348aea1b0ab0e5235133e

Quelldatensatz

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08071609B2