Cesium carbonate → ethyl (2E)-3-(5-{[(3R)-1-(benzyloxy)-6-oxo-3-piperidinyl]amino}-2-pyrazinyl)acrylate

HRID 2376081노트

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HRID 2376081 반응식
Cl[C:2]1[N:3]=[CH:4][C:5](/[CH:8]=[CH:9]/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[N:6][CH:7]=1.[NH2:15][C@H:16]1[CH2:21][N:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:19](=[O:30])[CH2:18][CH2:17]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:23]([O:22][N:20]1[C:19](=[O:30])[CH2:18][CH2:17][C@@H:16]([NH:15][C:2]2[N:3]=[CH:4][C:5](/[CH:8]=[CH:9]/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[N:6][CH:7]=2)[CH2:21]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 68960470(5R)-5-amino-1-(benzyloxy)-2-piperidinoneHCID 86603667Ethyl (2E)-3-(5-chloro-2-pyrazinyl)acrylate

생성물 1

HCID 86603704ethyl (2E)-3-(5-{[(3R)-1-(benzyloxy)-6-oxo-3-piperidinyl]amino}-2-pyrazinyl)acrylate수율 43.2%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

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온도
95 °C

실험 절차

Ethyl (2E)-3-(5-chloro-2-Pyrazinyl)acrylate (250 mg, 1.18 mmol) and (5R)-5-amino-1-(benzyloxy)-2-piperidinone (388 mg, 1.86 mmol) were combined in 1,4-dioxane (4 mL) at ambient temperature. To this solution were added palladium(II) acetate (18 mg, 0.8 mmol) and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (46 mg, 0.1 mmol) at the same temperature and the mixture was stirred for 5 minutes. To the resulting mixture was added cesium carbonate (536 mg, 1.86 mmol) and the mixture was heated at 95° C. for 24 hrs. The reaction mixture was evaporated in vacuo and the residue was partitioned between water and EtOAc. The organic layer was separated, washed water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography (CHCl3/methanol=95/1) to give ethyl (2E)-3-(5-{[(3R)-1-(benzyloxy)-6-oxo-3-piperidinyl]amino}-2-pyrazinyl)acrylate (202 mg, 43%) as an amorphous solid.

후처리

  1. customThe reaction mixture was evaporated in vacuo
  2. customthe residue was partitioned between water and EtOAc
  3. customThe organic layer was separated
  4. washwashed water and brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated in vacuo
  7. customThe residue was purified by silica gel column chromatography (CHCl3/methanol=95/1)

출처 및 근거

ORD 기록
ord-b5436d803bb54ec1b3f0f0a7d2de7ed4
출처 데이터셋
uspto-grants-2008_12
특허 번호
US07465731B2

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