1-Chloro-2-methylpropyl propanoate → (2-(((4-(1,3-dihydro-1-oxo-2H-isoindol-2-yl)butyl)(2-methyl-1-(1-oxopropoxy)propoxy)phosphinyl)methyl)-4-phenylbutanoyl)-L-leucine N-phenylamide

HRID 1489793

반응식

HRID 1489793 반응식
[C:1]([O:5][CH:6](Cl)[CH:7]([CH3:9])[CH3:8])(=[O:4])[CH2:2][CH3:3].[C:11]1([NH:17][C:18](=[O:54])[C@H:19]([CH2:50][CH:51]([CH3:53])[CH3:52])[NH:20][C:21](=[O:49])[CH:22]([CH2:31][P:32]([CH2:35][CH2:36][CH2:37][CH2:38][N:39]2[CH2:47][C:46]3[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=3)[C:40]2=[O:48])([OH:34])=[O:33])[CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>[I-].C([N+](CCCCCC)(CCCCCC)CCCCCC)CCCCC.C(OCC)(=O)C>[C:11]1([NH:17][C:18](=[O:54])[C@H:19]([CH2:50][CH:51]([CH3:52])[CH3:53])[NH:20][C:21](=[O:49])[CH:22]([CH2:31][P:32]([CH2:35][CH2:36][CH2:37][CH2:38][N:39]2[CH2:47][C:46]3[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=3)[C:40]2=[O:48])([O:34][CH:6]([O:5][C:1](=[O:4])[CH2:2][CH3:3])[CH:7]([CH3:9])[CH3:8])=[O:33])[CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

참가 물질

5

반응물 2

HCID 126610101-Chloro-2-methylpropyl propanoateHCID 57084392(2-(((4-(1,3-Dihydro-1-oxo-2H-isoindol-2-yl)butyl)hydroxyphosphinyl)methyl)-4-phenylbutanoyl)-L-leucine N-phenylamide

생성물 1

HCID 57064548(2-(((4-(1,3-dihydro-1-oxo-2H-isoindol-2-yl)butyl)(2-methyl-1-(1-oxopropoxy)propoxy)phosphinyl)methyl)-4-phenylbutanoyl)-L-leucine N-phenylamide수율 32%

시약·촉매·용매 2

HCID 75056Tetrahexylammonium iodide촉매HCID 8857Ethyl Acetate용매

실험 절차

1-Chloroisobutyl propionate (0.20 mL) was added to a mixture of 4 Å molecular sieves (125 mg), tetra-n-hexylammonium iodide (40 mg, 0.083 mmol), and (2-(((4-(1,3-Dihydro-1-oxo-2H-isoindol-2-yl)butyl)hydroxyphosphinyl)methyl)-4-phenylbutanoyl)-L-leucine N-phenylamide (50 mg, 0.081 mmol).6The mixture was warmed in an oil bath at 65°-70° C. for 7 h, then allowed to stand at room temperature overnight. The mixture was diluted into ethyl acetate (25 mL) and washed with 2N aqueous hydrochloric acid (25 mL) and saturated aqueous sodium chloride, and the organic layer was dried (sodium sulfate), decanted, and evaporated. The crude product was purified by flash column chromatography on silica gel (3 g) eluting with 20% acetone/dichloromethane to give 19 mg.(32% yield) of (2-(((4-(1,3-dihydro-1-oxo-2H-isoindol-2-yl)butyl)(2-methyl-1-(1-oxopropoxy)propoxy)phosphinyl)methyl)-4-phenylbutanoyl)-L-leucine N-phenylamide.

후처리

  1. temperaturewas warmed in an oil bath at 65°-70° C. for 7 h
  2. washwashed with 2N aqueous hydrochloric acid (25 mL) and saturated aqueous sodium chloride
  3. dry with materialthe organic layer was dried (sodium sulfate)
  4. customdecanted
  5. customevaporated
  6. customThe crude product was purified by flash column chromatography on silica gel (3 g)
  7. washeluting with 20% acetone/dichloromethane
  8. customto give 19 mg

출처 및 근거

ORD 기록
ord-15281153d9024d7d8e360e612d5177f7
출처 데이터셋
uspto-grants-1997_10
특허 번호
US05679700

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