Ammonia → (2R,5R)-5-(6-Amino-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine

HRID 474095ノート

反応式

HRID 474095 の反応式
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]=1

参加物

6

反応物 3

HCID 222AmmoniaHCID 11430Potassium CarbonateHCID 86668028[(2R,5R)-5-(6-Bromo-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester

生成物 1

HCID 68108751(2R,5R)-5-(6-Amino-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine

試薬・触媒・溶媒 2

HCID 8070N,N'-Dimethylethylenediamine触媒HCID 174Ethylene Glycol溶媒

反応条件

温度
60 °C

実験手順

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.

後処理

  1. customThe flask was sealed
  2. customA green solution was obtained
  3. customThe mixture was partitioned between water and EtOAc
  4. extractionThe aq. phase was extracted with EtOAc
  5. washthe combined org layers were washed with brine
  6. dry with materialdried with Na2SO4
  7. customevaporated

出典と根拠

ORDレコード
ord-725060aeb00e4dcdb8f87f3c4fb3148a
出典データセット
uspto-grants-2014_01
特許番号
US08637508B2

反応ノート

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