Реакция #614926

ord-5b13cb477d9b4c94b0f47e1f854227c9

Растворители

Условия реакции

Подробные условия
See reaction.notes.procedure_details.

Обработка

  1. 1
    workup.STIRRINGThe reaction mixture was stirred at rt for 1 h
  2. 2
    ДругоеThe organic layer was separated
  3. 3
    Промывкаwashed successively with aq. NaHCO3 solution, brine, and 1N HCl solution
  4. 4
    СушкаThe organics were dried over MgSO4
  5. 5
    Концентрированиеconcentrated in vacuo
  6. 6
    ДругоеThe resulting residue was purified by flash chromatography (eluting with 20% EtOAc/DCM)

Методика

To a solution of (2S,4S)-1-(tert-butoxycarbonyl)-4-((4-(methoxycarbonyl)benzyl)oxy)pyrrolidine-2-carboxylic acid (1.2 g, 3.2 mmol) in DMF (10 mL) was added EDC (0.91 g, 4.7 mmol) and 3H-[1,2,3]-triazolo[4,5-b]pyridin-3-ol (0.43 g, 3.2 mmol). The reaction mixture was stirred at rt for 5 min and treated with a solution of (R)-1,2,3,4-tetrahydronaphthalen-1-amine (0.54 g, 3.6 mmol) in DMF (5 mL) and 4-methylmorpholine (0.70 mL, 6.3 mmol). The reaction mixture was stirred at rt for 1 h and diluted with ethyl acetate and brine. The organic layer was separated and washed successively with aq. NaHCO3 solution, brine, and 1N HCl solution. The organics were dried over MgSO4 and concentrated in vacuo. The resulting residue was purified by flash chromatography (eluting with 20% EtOAc/DCM) to afford the title compound as a white solid (1.3 g, 81%). 1H NMR (CDCl3) δ 7.99 (d, J=8.4 Hz, 2H), 7.33 (d, J=6.8 Hz, 2H), 7.13-6.94 (m, 3H), 6.85-6.80 (m, 1H), 5.21-5.01 (m, 1H), 4.49-4.33 (m, 2H), 4.11 (d, J=3.1 Hz, 1H), 3.93 (s, 3H), 3.70-3.41 (m, 2H), 2.74 (d, J=3.3 Hz, 2H), 2.05 (s, 2H), 1.90-1.68 (m, 3H), 1.58 (s, 1H), 1.45 (s, 10H); MS(ESI+) m/z 509.5 (M+H)+.

Источник

DOI: 10.6084/m9.figshare.5104873.v1Патент: US09345740B2uspto-grants-2016_05