반응 #162645

ord-194c497a9ff64d559d0fd2a79c8c5b0f

용매

반응 조건

온도
120°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타to give a yellow biphasic solution
  2. 2
    기타The solution was sparged with nitrogen for 10 minutes
  3. 3
    기타The vial was sealed
  4. 4
    온도The vessel was then cooled to room temperature
  5. 5
    여과the reaction mixture was filtered through Celite™
  6. 6
    세척The filter cake was washed with ethyl acetate
  7. 7
    세척the filtrate was washed with saturated sodium chloride
  8. 8
    농축concentrated under reduced pressure
  9. 9
    기타to provide a brown oil
  10. 10
    세척was eluted with 5-90% acetonitrile in water (0.05% TFA buffer)

실험 절차

A microwave vial was charged with 1-(6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-2-chloropyrimidin-4-yl)-N,N-dimethylmethanamine (0.080 g, 0.283 mmol) and sodium carbonate (2M in water, 0.425 mL, 0.849 mmol). DME (1.5 mL) was then added to give a yellow biphasic solution. The solution was sparged with nitrogen for 10 minutes, and tetrakis(triphenylphosphine)palladium(0) (0.020 g, 0.017 mmol) and 1-(pyridin-3-yl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (0.106 g, 0.311 mmol) were added. The vial was sealed and heated to 120° C. for 2 hours via microwave. The vessel was then cooled to room temperature and the reaction mixture was filtered through Celite™. The filter cake was washed with ethyl acetate and the filtrate was washed with saturated sodium chloride and concentrated under reduced pressure to provide a brown oil. The crude product was added to a HPLC column and was eluted with 5-90% acetonitrile in water (0.05% TFA buffer) to provide the mono-TFA salt of 1-(4-(4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-6-((dimethylamino)methyl)pyrimidin-2-yl)phenyl)-3-(pyridin-3-yl)urea (0.097 g, 75%) as a light yellow solid. HRMS; [M+H]+ Obs'd=460.2454, [M+H]+ Calc'd=460.2455.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08835429B2uspto-grants-2014_09