تفاعل #41435

ord-3fe9bcf0c09d4dee8da87d8a5cf7a5e0

المذيبات

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىwas stirrred at r.t. for another h
  2. 2
    استخلاصthe mixture was extracted with EtOAc (2×50 mL)
  3. 3
    غسيلthe organic phase was washed with 10% NaHSO4 (aq), brine
  4. 4
    تجفيفdried over MgSO4
  5. 5
    ترشيحfiltered
  6. 6
    أخرىevaporated

الإجراء التجريبي

(1R,28)-1-(1-(4-chlorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-amine (126a) (256 mg, 0.63 mmol) dissolved in NMP (3.5 mL) was added to a solution of 2,2-difluoropropanoic acid (111 mg, 1.00 mmol), HATU (382 mg, 1.00 mmol) and DIPEA (0.438 mL, 2.51 mmol) in NMP (1.5 mL). The reaction mixture was stirred at r.t. for 2 h. Additional 2,2-difluoropropanoic acid (80 mg, 0.73 mmol), HATU (278 mg, 0.73 mmol) and DIPEA (0.25 mL, 1.4 mmol) in NMP (1.5 mL) was added. The reaction mixture was stirrred at r.t. for another h. Water (50 mL) was added, the mixture was extracted with EtOAc (2×50 mL), the organic phase was washed with 10% NaHSO4 (aq), brine, dried over MgSO4, filtered and evaporated to give a crude product that was purified by HPLC. The fractions containing the product was combined and freeze dried. Yield 197 mg (62%).

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US07728030B2uspto-grants-2010_06