Lopinavir → (1S,3S)-1-((1S)-1-{[(2,6-dimethylphenoxy)acetyl]amino}-2-phenylethyl)-3-{[(2S)-3-methyl-2-(2-oxotetrahydropyrimidin-1(2H)-yl)butanoyl]amino}-4-phenylbutyl 4-{[bis(benzyloxy)phosphoryl]oxy}-2,2-dimethylbutanoate

HRID 2238334노트

반응식

HRID 2238334 반응식
[P:1]([O:19][CH2:20][CH2:21][C:22]([CH3:27])([CH3:26])[C:23](Cl)=[O:24])([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[CH2:28]([C@H:35]([NH:60][C:61](=[O:73])[C@@H:62]([N:66]1[CH2:71][CH2:70][CH2:69][NH:68][C:67]1=[O:72])[CH:63]([CH3:65])[CH3:64])[CH2:36][C@H:37]([OH:59])[C@@H:38]([NH:46][C:47](=[O:58])[CH2:48][O:49][C:50]1[C:55]([CH3:56])=[CH:54][CH:53]=[CH:52][C:51]=1[CH3:57])[CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>ClCCl.CN(C)C1C=CN=CC=1>[CH2:4]([O:3][P:1]([O:19][CH2:20][CH2:21][C:22]([CH3:27])([CH3:26])[C:23]([O:59][C@H:37]([C@@H:38]([NH:46][C:47](=[O:58])[CH2:48][O:49][C:50]1[C:55]([CH3:56])=[CH:54][CH:53]=[CH:52][C:51]=1[CH3:57])[CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[CH2:36][C@@H:35]([NH:60][C:61](=[O:73])[C@@H:62]([N:66]1[CH2:71][CH2:70][CH2:69][NH:68][C:67]1=[O:72])[CH:63]([CH3:64])[CH3:65])[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:24])([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:2])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

참가 물질

5

반응물 2

HCID 92727LopinavirHCID 86616512Dibenzyl 4-chloro-3,3-dimethyl-4-oxobutyl phosphate

생성물 1

HCID 86616513(1S,3S)-1-((1S)-1-{[(2,6-dimethylphenoxy)acetyl]amino}-2-phenylethyl)-3-{[(2S)-3-methyl-2-(2-oxotetrahydropyrimidin-1(2H)-yl)butanoyl]amino}-4-phenylbutyl 4-{[bis(benzyloxy)phosphoryl]oxy}-2,2-dimethylbutanoate수율 56%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매2회

실험 절차

To a solution containing the product from Example 11C (0.538 mmol) dissolved in dichloromethane (1.0 mL) at 0° C., were added the product of Example 3 (0.085 g, 0.134 mmol) and 4-(dimethylamino)pyridine (0.066 g) and the reaction was allowed to warm to room temperature and was stirred for 16 hours. The reaction was diluted with dichloromethane, and the organic layer was washed with 10% citric acid, water and brine, dried over MgSO4, filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with a gradient starting with dichloromethane and ending with 5% methanol in ethyl acetate, to give the title compound (0.075 g, 56%).

후처리

  1. washthe organic layer was washed with 10% citric acid, water and brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by chromatography on silica gel
  6. washeluting with a gradient

출처 및 근거

ORD 기록
ord-0a1b77b6f4e543ed8371fc92dc3d897a
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07718633B2

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