반응 #49235

ord-b077e03fb39a4f5c879440f20aeb9e9a

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    workup.ADDITIONwas then added
  2. 2
    기타Preparation D, (20 mg, 0.046 mmol)
  3. 3
    workup.STIRRINGthe reaction mixture was stirred at rt overnight
  4. 4
    세척washed with H2O (50 mL) twice
  5. 5
    건조dried over Na2SO4
  6. 6
    농축concentrated

실험 절차

Step 5 (A): N1-((1S,2S)-1-((R)-4-benzhydrylmorpholin-3-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-N3,N3-dipropylisophthalamide. To a solution of 3-(dipropylcarbamoyl)benzoic acid (Preparation E, 14 mg, 0.055 mmol) in dichloromethane (1 mL) was added Hunig's base (18 mg, 0.14 mmol) to make a clear solution and HATU (25 mg, 0.064 mmol) was then added. After stirring for 20 min, the reaction mixture was added (1S,2S)-2-amino-1-((R)-4-benzhydrylmorpholin-3-yl)-3-(3,5-difluorophenyl)propan-1-ol (Preparation D, (20 mg, 0.046 mmol) and the reaction mixture was stirred at rt overnight. Dichloromethane (100 mL) was added and washed with H2O (50 mL) twice, dried over Na2SO4, and concentrated to give the title compound as a crude product ready for next step without purification: 1H NMR (CD3OD, 500 MHz) δ 0.71 (3H, m), 1.01 (3H, m), 1.52 (2H, m), 1.74 (2H, m), 2.52 (1H, d, J=5 Hz), 2.63 (2H, dd, J=5, 15 Hz), 2.71 (1H, m), 3.12-3.19 (3H, m), 3.44-3.49 (3H, m), 3.94-3.99 (2H, m),4.04 (1H, m), 4.58 (1H, m), 5.06 (1H, m), 5.50 (1H, s), 6.76 (1H, m), 6.92-6.95 (2H, m), 7.14-7.19 (3H, m), 7.25-7.32 (3H, m), 7.44 (2H, m), 7.49-7.55 (2H, m), 7.58 (2H, d, J=10 Hz), 7.63 (1H, s), 7.73-7.76 (1H, m).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US07745470B2uspto-grants-2010_06