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 1968917ノート

反応式

HRID 1968917 の反応式
[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

参加物

5

反応物 2

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

生成物 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-dimethylbutanoate収率 56%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒2 回

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-7dfcc622ac6c4f74a986e739d7b8dc1c
出典データセット
uspto-grants-2013_04
特許番号
US08426388B2

反応ノート

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