Ammonia → (2R,5R)-5-(6-Amino-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine
Reaction equation
C(OC(=O)[NH:7][C:8]1[C@:9]([CH3:26])([C:22]([F:25])([F:24])[F:23])[O:10][CH2:11][C@:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17](Br)[N:16]=2)([CH3:14])[N:13]=1)(C)(C)C.C([O-])([O-])=O.[K+].[K+].[NH3:34]>C(O)CO.CNCCNC>[NH2:34][C:17]1[N:16]=[C:15]([C@:12]2([CH3:14])[CH2:11][O:10][C@@:9]([CH3:26])([C:22]([F:25])([F:24])[F:23])[C:8]([NH2:7])=[N:13]2)[CH:20]=[CH:19][CH:18]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 60 °C
Procedure
To a suspension of (2R,5R)-5-(6-bromo-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine (6.0 g, 17.04 mmol, Example 8 step h), Cu2O (0.122 g, 0.852 mmol), K2CO3 (0.471 g, 3.41 mmol) and N,N′-dimethylethylenediamine (0.15 g, 1.704 mmol) were suspended in ethylene glycol (34 ml) were added 53 ml aq. NH3 (25% w). The flask was sealed and the suspension was stirred to 60° C. for 20 h. A green solution was obtained. It was occasionally necessary to shake the flask to make sure that all insoluble parts went in solution. The mixture was partitioned between water and EtOAc. The aq. phase was extracted with EtOAc, the combined org layers were washed with brine, dried with Na2SO4 and evaporated to give 5.11 g of a green resin, which was purified by chromatography on silica gel (DCM/1-4% (EtOH 25% aq NH3 9:1)) to give 2.77 g of the title compound as a colorless foam.
Workup
- customThe flask was sealed
- customA green solution was obtained
- customThe mixture was partitioned between water and EtOAc
- extractionThe aq. phase was extracted with EtOAc
- washthe combined org layers were washed with brine
- dry with materialdried with Na2SO4
- customevaporated
Sources & evidence
- ORD record
- ord-cbb6dee621734514a63b87fffc1b55c3
- Source dataset
- uspto-grants-2014_10
- Patent number
- US08865712B2
Reaction notes
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