Tert-butoxycarbonylalanine → (1S,3S)-1-((1S)-1-{[(2S)-2-(3-benzyl-2-oxoimidazolidin-1-yl)-3,3-dimethylbutanoyl]amino}-2-phenylethyl)-3-{[N-(methoxycarbonyl)-3-methyl-L-valyl]amino}-4-(4-pyridin-2-ylphenyl)butyl N-(tert-butoxycarbonyl)-L-alaninate

HRID 1174409노트

반응식

HRID 1174409 반응식
[CH2:1]([N:8]1[CH2:12][CH2:11][N:10]([C@@H:13]([C:55]([CH3:58])([CH3:57])[CH3:56])[C:14]([NH:16][C@@H:17]([CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C@@H:18]([OH:47])[CH2:19][C@@H:20]([NH:34][C:35]([C@@H:37]([NH:42][C:43](=[O:46])[O:44][CH3:45])[C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=3)=[CH:24][CH:23]=2)=[O:15])[C:9]1=[O:59])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:60]([O:64][C:65]([NH:67][C@H:68]([C:70](O)=[O:71])[CH3:69])=[O:66])([CH3:63])([CH3:62])[CH3:61].Cl.CN(C)CCCN=C=NCC>CN(C)C1C=CN=CC=1.CN(C)C=O>[C:60]([O:64][C:65]([NH:67][C@H:68]([C:70]([O:47][C@H:18]([C@@H:17]([NH:16][C:14](=[O:15])[C@@H:13]([N:10]1[CH2:11][CH2:12][N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:9]1=[O:59])[C:55]([CH3:58])([CH3:57])[CH3:56])[CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)[CH2:19][C@@H:20]([NH:34][C:35](=[O:36])[C@H:37]([C:38]([CH3:41])([CH3:40])[CH3:39])[NH:42][C:43]([O:44][CH3:45])=[O:46])[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=2)=[CH:24][CH:23]=1)=[O:71])[CH3:69])=[O:66])([CH3:62])([CH3:63])[CH3:61]

참가 물질

6

반응물 3

HCID 85082Tert-butoxycarbonylalanine2회HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2회HCID 11274374A-792611

생성물 1

HCID 86599589(1S,3S)-1-((1S)-1-{[(2S)-2-(3-benzyl-2-oxoimidazolidin-1-yl)-3,3-dimethylbutanoyl]amino}-2-phenylethyl)-3-{[N-(methoxycarbonyl)-3-methyl-L-valyl]amino}-4-(4-pyridin-2-ylphenyl)butyl N-(tert-butoxycarbonyl)-L-alaninate수율 82.6%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매

실험 절차

To a solution containing the compound of Example 111 (0.100 g, 0.124 mmol), N-(tert-butoxycarbonyl) L-alanine (0.028 g, 0.147 mmol)), and 4(dimethylamino)pyridine (0.018 g, 0.147 mmol) in N,N-dimethylformamide (1.0 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDAC) (0.029 g, 0.151 mmol) and the mixture was stirred at room temperature for 2 hours. Two subsequent additions of N-(tert-butoxycarbonyl) L-alanine (0.028 g) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDAC) (0.029 g) were made at two hour intervals. The solvent was evaporated and the reaction mixture 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 chloroform and ending with 66% ethyl acetate in chloroform, to give the title compound (0.100 g, 82%).

후처리

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

출처 및 근거

ORD 기록
ord-1c35c8944eb74f2abf94408bb3af9a7a
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07834043B2

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