Pyridine → 2,4-Bis-(N-(Cbz-valinyl)amino)-1,5-diphenyl-3-pentyl 4-(chloromethyl)benzoate

HRID 1078142노트

반응식

HRID 1078142 반응식
[C:1]([NH:11][C@H:12]([C:16]([NH:18][CH:19]([CH:27]([OH:54])[CH:28]([NH:36][C:37](=[O:53])[C@H:38]([CH:50]([CH3:52])[CH3:51])[NH:39][C:40]([O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:41])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:17])[CH:13]([CH3:15])[CH3:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[Cl:55][CH2:56][C:57]1[CH:65]=[CH:64][C:60]([C:61](Cl)=[O:62])=[CH:59][CH:58]=1.N1C=CC=CC=1>C(Cl)(Cl)Cl.C(Cl)Cl.CO>[Cl:55][CH2:56][C:57]1[CH:65]=[CH:64][C:60]([C:61]([O:54][CH:27]([CH:19]([NH:18][C:16](=[O:17])[C@H:12]([CH:13]([CH3:14])[CH3:15])[NH:11][C:1]([O:3][CH2:4][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=2)=[O:2])[CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:28]([NH:36][C:37](=[O:53])[C@H:38]([CH:50]([CH3:52])[CH3:51])[NH:39][C:40]([O:42][CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[O:41])[CH2:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[O:62])=[CH:59][CH:58]=1

참가 물질

7

반응물 3

HCID 1049PyridineHCID 701364-(Chloromethyl)benzoyl chlorideHCID 3011026benzyl N-[(1S)-1-[[1-benzyl-3-[[(2S)-2-(benzyloxycarbonylamino)-3-methyl-butanoyl]amino]-2-hydroxy-4-phenyl-butyl]carbamoyl]-2-methyl-propyl]carbamate

생성물 1

HCID 228455672,4-Bis-(N-(Cbz-valinyl)amino)-1,5-diphenyl-3-pentyl 4-(chloromethyl)benzoate수율 46.1%

시약·촉매·용매 3

HCID 887Methanol용매2회HCID 6212Chloroform용매HCID 6344Dichloromethane용매4회

실험 절차

The resultant compound of Example 70 (1.3 g, 1.76 mmol) was combined with 4-(chloromethyl)benzoyl chloride (1.0 g, 5.3 mmol) and pyridine (418 mg, 5.3 mmol) in 10 mL of freshly distilled methylene chloride. The reaction mixture was heated at reflux under nitrogen for approximately 10 h and then diluted with 150 mL of chloroform. The chloroform solution was washed with 75 mL of water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue (2.1 g) was taken up in ~10 mL of chloroform and applied to a 1.8×45 cm column of 40 mesh silica gel. The column was eluted @~5 p.s.i. sequentially with 200 mL of methylene chloride, 250 mL of 0.5% methanol in methylene chloride and 600 mL of 1% methanol in methylene chloride to give 721 mg (46% yield) of the title compound; FAB MS M/Z: 889 (M+H)+. The 300 MHz 1H NMR spectrum was consistent with the assigned structure.

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux under nitrogen for approximately 10 h
  3. washThe chloroform solution was washed with 75 mL of water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. washThe column was eluted @~5 p.s.i

출처 및 근거

ORD 기록
ord-268fc2c9bf2e4a298b1672e14f090ace
출처 데이터셋
uspto-grants-1996_08
특허 번호
US05545750

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