Reaktion #168778

Reaktionsgleichung

[(S)-5-(5-amino-2-fluoro-phenyl)-5-difluoromethyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-yl]-carbamic acid tert-butyl ester

5-cyano-2-pyridinecarboxylic acid

HOAT

EDC

DIPEA

→

title compound

Ausbeute 98.2%

((S)-5-{5-[(5-Cyano-pyridine-2-carbonyl)-amino]-2-fluoro-phenyl}-5-difluoromethyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-yl)-carbamic acid tert-butyl ester

Ausbeute 98.2%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction mixture was then partitioned between saturated aqueous NaHCO3 solution and EtOAc
2. 2
   SonstigeThe layers were separated
3. 3
   Waschenwashed with saturated aqueous NaHCO3 solution, brine and EtOAc
4. 4
   TrocknenThe combined organic layers were dried over MgSO4.H2O
5. 5
   Sonstigeevaporated
6. 6
   SonstigeThe crude product was purified on a silica gel column
7. 7
   Waschenby eluting with hexane/EtOAc 3/1->1.5/1

Vorschrift

A solution of [(S)-5-(5-amino-2-fluoro-phenyl)-5-difluoromethyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-yl]-carbamic acid tert-butyl ester (51.2 mg, 0.137 mmol), 5-cyano-2-pyridinecarboxylic acid (30.5 mg, 0.206 mmol) and HOAT (33.6 mg, 0.247 mmol) in 0.6 mL DMF was cooled to 0-5° C. EDC (39.4 mg, 0.206 mmol) and DIPEA (35.4 mg, 0.274 mmol) were added. The resulting solution was allowed to warm up to rt over night. The reaction mixture was then partitioned between saturated aqueous NaHCO3 solution and EtOAc. The layers were separated, washed with saturated aqueous NaHCO3 solution, brine and EtOAc. The combined organic layers were dried over MgSO4.H2O and evaporated. The crude product was purified on a silica gel column by eluting with hexane/EtOAc 3/1->1.5/1 to give 67.7 mg of the title compound as a colorless resin.

Quelle