반응 #1714728

ord-fb800aad2de14d50a30a5ecb15e4668d

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타The mixture was bubbled with nitrogen for 10 min
  2. 2
    기타then microwaved at 150° C. for 30 min
  3. 3
    기타The crude reaction mixture
  4. 4
    세척followed by washings with water and brine
  5. 5
    건조The solution was dried over MgSO4
  6. 6
    기타Purification
  7. 7
    기타by prep-HPLC afforded a solid
  8. 8
    기타Removal of the volatiles
  9. 9
    기타was purified by prep-HPLC

실험 절차

To a mixture of [3-(4-iodo-benzoyl)-3-aza-bicyclo[3.1.0]hex-6-yl]-carbamic acid tert-butyl ester (100 mg, 0.234 mmol) and 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (100 mg, 0.234 mmol) in DME (2 mL) was added Pd(dppf)2Cl2.CH2Cl2 (10 mg, 0.012 mmol) and Cs2CO3 (351 mg, 0.702 mmol). The mixture was bubbled with nitrogen for 10 min then microwaved at 150° C. for 30 min. LCMS checked that the reaction was completed. The crude reaction mixture was diluted with ethyl acetate followed by washings with water and brine. The solution was dried over MgSO4. Purification by prep-HPLC afforded a solid. The solid was stirred with 4 N HCl/dioxane (3 mL) for 3 hr at room temperature. Removal of the volatiles led to a residue that was purified by prep-HPLC to afford (6-amino-3-aza-bicyclo[3.1.0]hex-3-yl)-(4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-methanone (30 mg, yield 26%).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08785632B2uspto-grants-2014_07