Reaktion #41435

Reaktionsgleichung

2,2-difluoropropanoic acid

HATU

DIPEA

2,2-difluoropropanoic acid

HATU

DIPEA

(1R,28)-1-(1-(4-chlorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-amine

(1R,2S)-1-(1-(4-chlorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-amine

→

crude product

N-((1R,2S)-1-(1-(4-chlorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-yl)-2,2-difluoropropanamide

Lösungsmittel

Water

NMP

NMP

NMP

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas stirrred at r.t. for another h
2. 2
   Extraktionthe mixture was extracted with EtOAc (2×50 mL)
3. 3
   Waschenthe organic phase was washed with 10% NaHSO4 (aq), brine
4. 4
   Trocknendried over MgSO4
5. 5
   Filtrationfiltered
6. 6
   Sonstigeevaporated

Vorschrift

(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%).

Quelle