Dichloromethane → 4-Methyl-7H-pyrrolo(2,3-d)pyrimidine

Temperature

55 °C

To 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (17, 5.03 g, 32.8 mmol) in 100 mL of toluene, [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) 1:1 complex with dichloromethane (0.627 g, 0.328 mmol) was added under nitrogen. After stirring for 10 minutes, methylmagnesium bromide (62.9 mL, 3.00 M in ether, 189 mmol) was added slowly. The reaction was heated at 55° C. overnight, then cooled to −70 to −80° C. and quenched by adding ammonium chloride dropwise. Then 1N hydrochloric acid was added and the pH was adjusted to 7-8 with addition of saturated sodium bicarbonate. This was extracted 3× with ethyl acetate. The combined organic layer was washed with saturated ammonium chloride and brine, then dried with magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography, eluting with ethyl acetate and dichloromethane, then methanol and dichloromethane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound as a tan solid (18). MS (ESI) [M+H′]′=134.

1. temperaturecooled to −70 to −80° C.
2. customquenched
3. additionby adding ammonium chloride dropwise
4. additionThen 1N hydrochloric acid was added
5. additionthe pH was adjusted to 7-8 with addition of saturated sodium bicarbonate
6. extractionThis was extracted 3× with ethyl acetate
7. washThe combined organic layer was washed with saturated ammonium chloride and brine
8. dry with materialdried with magnesium sulfate
9. filtrationfiltered
10. concentrationthe filtrate concentrated under vacuum
11. customThe resulting material was purified by silica gel column chromatography
12. washeluting with ethyl acetate and dichloromethane
13. concentrationconcentrated under vacuum

ORD record

ord-a488bcb01e42419d9cc047031096ddfa

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096593B2