Methanol → 2,4-Bis-(N-(Cbz-valinyl)amino)-1,5-diphenyl-3-pentyl alpha-bromoacetate

HRID 847644노트

반응식

HRID 847644 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].N1C=CC=CC=1.[Br:61][CH2:62][C:63](Br)=[O:64].CO>C(Cl)Cl.C(Cl)(Cl)Cl>[Br:61][CH2:62][C:63]([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]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2])[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[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:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)=[O:64]

참가 물질

7

반응물 4

HCID 887MethanolHCID 1049PyridineHCID 61147Bromoacetyl bromideHCID 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 228455682,4-Bis-(N-(Cbz-valinyl)amino)-1,5-diphenyl-3-pentyl alpha-bromoacetate수율 55%

시약·촉매·용매 2

HCID 6212Chloroform용매2회HCID 6344Dichloromethane용매

실험 절차

The resultant compound of Example 70 (600 mg, 0.81 mmol) was dissolved in 8 mL of methylene chloride and 72 μL (0.9 mmol) of pyridine. The solution was cooled in an ice bath with stirring under a nitrogen atmosphere. α-Bromoacetyl bromide (181 mg, 0.9 mmol) was added in one portion and the ice bath was removed. The reaction mixture was stirred at ambient temperature for 3 h and then diluted with 150 mL of chloroform. The chloroform solution was washed with 150 mL of water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue (644 mg) was taken up in a mixture of chloroform and methanol and adsorbed onto approximately 1.5 g of 40 mesh silica gel in vacuo @40° C. The silica gel with the product adsorbed onto it was applied to a 1.0×40 cm column of 40 mesh silica gel and the column was eluted @~5 p.s.i. sequentially with 100 mL of chloroform and 100 mL of 1% methanol in chloroform to give 378 mg (55% yield) of the title compound; FAB MS M/Z: 859 (M+H)+. The 300 MHz 1NMR spectrum was consistent with the assigned structure.

후처리

  1. temperatureThe solution was cooled in an ice bath
  2. customthe ice bath was removed
  3. stirringThe reaction mixture was stirred at ambient temperature for 3 h
  4. additiondiluted with 150 mL of chloroform
  5. washThe chloroform solution was washed with 150 mL of water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. additionThe residue (644 mg) was taken up in a mixture of chloroform and methanol
  10. customadsorbed onto approximately 1.5 g of 40 mesh silica gel in vacuo @40° C
  11. washthe column was eluted @~5 p.s.i

출처 및 근거

ORD 기록
ord-1e400b806df446b59204f60ba7fe928d
출처 데이터셋
uspto-grants-1992_08
특허 번호
US05142056

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