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 1968917Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1968917
[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

Komponenten

5

Edukt 2

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

Produkt 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-dimethylbutanoateAusbeute 56 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

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%).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-7dfcc622ac6c4f74a986e739d7b8dc1c
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08426388B2

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