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 2238330ノート

反応式

HRID 2238330 の反応式
[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]

参加物

6

反応物 3

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

生成物 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-dimethylbutanoate収率 81%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-1662f0fa56cb49b382bf42ccbdd6b754
出典データセット
uspto-grants-2010_05
特許番号
US07718633B2

反応ノート

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