Dimethyl Sulfoxide → (2s)-n-{(1s,3s,4s)-1-Benzyl-4-{[(2,6-dimethylphenoxy)acetyl]amino}-3-[(methylthio)methoxy]-5-phenylpentyl}-3-methyl-2-(2-oxotetrahydropyrimidin-1(2h)-yl)butanamide

HRID 1968905Notes

Reaction equation

HRID 1968905 reaction equation
[CH2:1]([C@H:8]([NH:33][C:34](=[O:46])[C@@H:35]([N:39]1[CH2:44][CH2:43][CH2:42][NH:41][C:40]1=[O:45])[CH:36]([CH3:38])[CH3:37])[CH2:9][C@H:10]([OH:32])[C@@H:11]([NH:19][C:20](=[O:31])[CH2:21][O:22][C:23]1[C:28]([CH3:29])=[CH:27][CH:26]=[CH:25][C:24]=1[CH3:30])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:47][S:48]([CH3:50])=O.C(OC(=O)C)(=O)C>C(O)(=O)C>[CH2:1]([C@H:8]([NH:33][C:34](=[O:46])[C@@H:35]([N:39]1[CH2:44][CH2:43][CH2:42][NH:41][C:40]1=[O:45])[CH:36]([CH3:38])[CH3:37])[CH2:9][C@H:10]([O:32][CH2:47][S:48][CH3:50])[C@@H:11]([NH:19][C:20](=[O:31])[CH2:21][O:22][C:23]1[C:24]([CH3:30])=[CH:25][CH:26]=[CH:27][C:28]=1[CH3:29])[CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 7918Acetic AnhydrideHCID 92727Lopinavir

Product 1

HCID 42638008(2s)-n-{(1s,3s,4s)-1-Benzyl-4-{[(2,6-dimethylphenoxy)acetyl]amino}-3-[(methylthio)methoxy]-5-phenylpentyl}-3-methyl-2-(2-oxotetrahydropyrimidin-1(2h)-yl)butanamideYield 64%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of the compound of Example 3 (3.0 g, 4.8 mmol), DMSO (18 mL), and acetic acid (3.6 mL) at room temperature was added acetic anhydride (23 mL), and the reaction was stirred for 48 hours at room temperature. The reaction was quenched with ice and 10% Na2CO3 was added to adjust the pH to 7. The mixture was extracted with ethyl acetate and washed with 10% Na2CO3 and brine. The organic was dried over Na2SO4, filtered and evaporated to give the crude product, which was chromatographed on silica gel eluting first with 25-100% ethyl acetate in dichloromethane to give the title compound (2.1 g, 64% yield).

Workup

  1. customThe reaction was quenched with ice and 10% Na2CO3
  2. additionwas added
  3. extractionThe mixture was extracted with ethyl acetate
  4. washwashed with 10% Na2CO3 and brine
  5. dry with materialThe organic was dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customto give the crude product, which
  9. customwas chromatographed on silica gel eluting first with 25-100% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-78770417e7674de5a6b5651ef92c1437
Source dataset
uspto-grants-2013_04
Patent number
US08426388B2

Reaction notes

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