1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (1S,3S)-3-[(N-{[[(2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl}-L-valyl)amino]-4-phenyl-1-((1S)-2-phenyl-1-{[(1,3-thiazol-5-ylmethoxy)carbonyl]amino}ethyl)butyl 4-[(di-tert-butoxyphosphoryl)oxy]-3,3-dimethylbutanoate

HRID 2238330Notes

Reaction equation

HRID 2238330 reaction equation
[CH2:1]([C@H:8]([NH:30][C:31](=[O:50])[C@H:32]([CH:47]([CH3:49])[CH3:48])[NH:33][C:34]([N:36]([CH2:38][C:39]1[N:40]=[C:41]([CH:44]([CH3:46])[CH3:45])[S:42][CH:43]=1)[CH3:37])=[O:35])[CH2:9][C@H:10]([OH:29])[C@@H:11]([NH:19][C:20]([O:22][CH2:23][C:24]1[S:28][CH:27]=[N:26][CH:25]=1)=[O:21])[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.[C:51]([O:55][P:56]([O:63][CH2:64][C:65]([CH3:71])([CH3:70])[CH2:66][C:67](O)=[O:68])([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])([CH3:54])([CH3:53])[CH3:52].CCN=C=NCCCN(C)C>CN(C)C1C=CN=CC=1.CN(C=O)C>[C:51]([O:55][P:56]([O:63][CH2:64][C:65]([CH3:71])([CH3:70])[CH2:66][C:67]([O:29][C@H:10]([C@@H:11]([NH:19][C:20]([O:22][CH2:23][C:24]1[S:28][CH:27]=[N:26][CH:25]=1)=[O:21])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:9][C@@H:8]([NH:30][C:31](=[O:50])[C@H:32]([CH:47]([CH3:49])[CH3:48])[NH:33][C:34]([N:36]([CH2:38][C:39]1[N:40]=[C:41]([CH:44]([CH3:45])[CH3:46])[S:42][CH:43]=1)[CH3:37])=[O:35])[CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:68])([O:58][C:59]([CH3:60])([CH3:61])[CH3:62])=[O:57])([CH3:54])([CH3:53])[CH3:52]

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide2×HCID 392622RitonavirHCID 860938834-[(Di-tert-butoxyphosphoryl)oxy]-3,3-dimethylbutanoic acid2×

Product 1

HCID 87319133(1S,3S)-3-[(N-{[[(2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl}-L-valyl)amino]-4-phenyl-1-((1S)-2-phenyl-1-{[(1,3-thiazol-5-ylmethoxy)carbonyl]amino}ethyl)butyl 4-[(di-tert-butoxyphosphoryl)oxy]-3,3-dimethylbutanoateYield 81%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution containing the compound of Example 1 (0.10 g, 0.14 mmol), the product from Example 10D (0.045 g), and 4-(dimethylamino)pyridine (0.017 g) in DMF (1.4 mL) was added EDAC (0.027 g), and the mixture was stirred at room temperature for 68 hours. Additional product from Example 10D (0.045 g) and EDAC (0.027 g) were added and the reaction mixture was stirred at room temperature for 18 hours. The solvent was evaporated and the concentrate was partitioned between ethyl acetate and aqueous NaHCO3. The organic layer was washed with brine, dried over MgSO4, filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with a gradient starting with ethyl acetate and ending with 5% methanol in ethyl acetate, to give the title compound (0.115 g, 81% yield).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 18 hours
  2. customThe solvent was evaporated
  3. customthe concentrate was partitioned between ethyl acetate and aqueous NaHCO3
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by chromatography on silica gel
  9. washeluting with a gradient

Sources & evidence

ORD record
ord-1662f0fa56cb49b382bf42ccbdd6b754
Source dataset
uspto-grants-2010_05
Patent number
US07718633B2

Reaction notes

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