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 2238330노트

반응식

HRID 2238330 반응식
[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]

참가 물질

6

반응물 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide2회HCID 392622RitonavirHCID 860938834-[(Di-tert-butoxyphosphoryl)oxy]-3,3-dimethylbutanoic acid2회

생성물 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-dimethylbutanoate수율 81%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-1662f0fa56cb49b382bf42ccbdd6b754
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07718633B2

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