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

HRID 474095노트

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HRID 474095 반응식
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

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 2

HCID 8070N,N'-Dimethylethylenediamine촉매HCID 174Ethylene Glycol용매

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온도
60 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-725060aeb00e4dcdb8f87f3c4fb3148a
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637508B2

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