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

反応式

HRID 1489793 の反応式
[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

参加物

5

反応物 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

生成物 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-phenylamide収率 32%

試薬・触媒・溶媒 2

HCID 75056Tetrahexylammonium iodide触媒HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-15281153d9024d7d8e360e612d5177f7
出典データセット
uspto-grants-1997_10
特許番号
US05679700

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