Reaktion #168764

Reaktionsgleichung

EDC

[5-(5-amino-2-fluoro-phenyl)-5-difluoromethyl-2-methyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester

5-cyano-2-pyridinecarboxylic acid

HOAT

DIPEA

→

title compound

(5-{5-[(5-Cyano-pyridine-2-carbonyl)-amino]-2-fluoro-phenyl}-5-difluoromethyl-2-methyl-5,6-dihydro-2H-[1,4]oxazin-3-yl)-carbamic acid tert-butyl ester

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added
2. 2
   Sonstigethe mixture was partitioned between saturated aqueous NaHCO3 solution and EtOAc
3. 3
   SonstigeThe layers were separated
4. 4
   Waschenwashed with saturated aqueous NaHCO3 solution, brine and EtOAc
5. 5
   TrocknenThe combined organic layers were dried over MgSO4.H2O
6. 6
   Sonstigeevaporated
7. 7
   SonstigeThe crude product was purified on a silica gel column
8. 8
   Waschenby eluting with hexane/EtOAc 3/1->2/1

Vorschrift

A solution of [5-(5-amino-2-fluoro-phenyl)-5-difluoromethyl-2-methyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester (140 mg, 0.375 mmol), 5-cyano-2-pyridinecarboxylic acid (83 mg, 0.562 mmol) and HOAT (92 mg, 0.675 mmol) in 2 mL DMF was cooled to 0-5° C. EDC (108 mg, 0.562 mmol) followed by DIPEA (97 mg, 0.750 mmol) was added. The reaction mixture was allowed to warm up to room temperature. After 135 minutes, the mixture was 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->2/1 to give the title compound as a diasteromeric mixture (white foam).

Quelle