Methyl iodide → 2-[5-(2,4-Diaminopyrimidin-5-yloxy)-4-isopropyl-2-methoxy-phenyl]-propan-2-ol

Temperature

0 °C

To a solution of methylmagnesium bromide (83.4 mmol, 27.8 ml, 3.0 M in Et2O) in 83 mL THF at 0° C. was added 1-[5-(2,4-diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-phenyl]-ethanone (2.523 g, 8.3 mmol, from Example 16) in portions. After 16 h the mixture was cooled to 0° C. and was quenched by the addition 10% NH4Cl. H2O was added and the mixture was extracted with ethyl acetate. The combined organics were washed with H2O, washed with brine, dried over NaHCO3, filtered and concentrated in vacuo. The crude solid was taken up in 31 ml DMF. K2CO3 (0.65 g, 4.7 mmol) and iodomethane (0.098 ml, 1.6 mmol) were added and the mixture was warmed to 50° C. Additional portions of iodomethane (0.019 mL, 0.6 mmol) was added at 1, 2 and 3 hr. After 16 h the mixture was cooled and 10% NH4Cl and extracted with ethyl acetate. The combined organics were washed with H2O, washed with brine, dried with Na2SO4, filtered and concentrated in vacuo to give 2-[5-(2,4-diaminopyrimidin-5-yloxy)-4-isopropyl-2-methoxy-phenyl]-propan-2-ol (0.711 g, yield) as a white solid. [MH]+=333.

1. customwas quenched by the addition 10% NH4Cl
2. additionH2O was added
3. extractionthe mixture was extracted with ethyl acetate
4. washThe combined organics were washed with H2O
5. washwashed with brine
6. dry with materialdried over NaHCO3
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. temperaturethe mixture was warmed to 50° C
10. temperatureAfter 16 h the mixture was cooled
11. extraction10% NH4Cl and extracted with ethyl acetate
12. washThe combined organics were washed with H2O
13. washwashed with brine
14. dry with materialdried with Na2SO4
15. filtrationfiltered
16. concentrationconcentrated in vacuo

ORD record

ord-483969fc0dd94f59b07ca1fa69430a37

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08008313B2