Ethyl 3-(4-pyridyl)-3-oxopropionate → (+/-) 2-(4-Oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-1H-isoindole-1,3(2H)-dione

HRID 217884노트

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HRID 217884 반응식
Cl.[NH2:2][C:3]1[CH:8]([N:9]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:19])[CH2:7][CH2:6][CH2:5][N:4]=1.C[O-].[Na+].[Na].[N:24]1[CH:29]=[CH:28][C:27]([C:30](=O)[CH2:31][C:32](OCC)=[O:33])=[CH:26][CH:25]=1>C1(C)C=CC=CC=1.CO>[O:33]=[C:32]1[N:4]2[CH2:5][CH2:6][CH2:7][CH:8]([N:9]3[C:10](=[O:19])[C:11]4[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=4)[C:17]3=[O:18])[C:3]2=[N:2][C:30]([C:27]2[CH:28]=[CH:29][N:24]=[CH:25][CH:26]=2)=[CH:31]1

참가 물질

7

반응물 4

HCID 2735202Ethyl 3-(4-pyridyl)-3-oxopropionateHCID 5360545SodiumHCID 10942334Sodium MethoxideHCID 67265827(+/-) 2-(2-Amino-3,4,5,6-tetrahydropyridin-3-yl)-1H-isoindole-1,3(2H)-dione hydrochloride

생성물 1

HCID 67265728(+/-) 2-(4-Oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-1H-isoindole-1,3(2H)-dione수율 34.1%

시약·촉매·용매 2

HCID 887Methanol용매HCID 1140Toluene용매

실험 절차

To a suspension of 9.166 g (32.77 mmol) of (+/−)2-(2-Amino-3,4,5,6-tetrahydropyridin-3-yl)-1H-isoindole-1,3(2H)-dione hydrochloride (1:1) in 50 mL of toluene was added sodium methanolate (freshly prepared from 0.754 g (32.77 mmol) of sodium in 10 mL of methanol and the reaction mixture was stirred at room temperature for 1 h. The mixture was evaporated to dryness, dissolved in 50 mL of toluene and 4.87 g (25.21 mmol) of ethyl 3-(pyridin-4-yl)-3-oxopropionate was added. The resulting solution was stirred under reflux for 12 h. The cooled solution was evaporated to remove solvent. The mixture was dissolved in dichloromethane, washed with a saturated aqueous solution of ammonium chloride, saturated aqueous sodium chloride, dried over sodium sulfate and evaporated to dryness. The residue was chromatographed on silica gel eluting with a mixture of dichloromethane/methanol/aqueous ammonia solution (29%) in the proportions 97/3/0.3 led to afford 3.2 g (34%) of the desired compound as a white powder.

후처리

  1. customThe mixture was evaporated to dryness
  2. dissolutiondissolved in 50 mL of toluene
  3. stirringThe resulting solution was stirred
  4. temperatureunder reflux for 12 h
  5. customThe cooled solution was evaporated
  6. customto remove solvent
  7. dissolutionThe mixture was dissolved in dichloromethane
  8. washwashed with a saturated aqueous solution of ammonium chloride, saturated aqueous sodium chloride
  9. dry with materialdried over sodium sulfate
  10. customevaporated to dryness
  11. customThe residue was chromatographed on silica gel eluting with a mixture of dichloromethane/methanol/aqueous ammonia solution (29%) in the proportions 97/3/0.3

출처 및 근거

ORD 기록
ord-4b088f9f6b1247588162c1ce7193caea
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08198287B2

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