Chloromethyl Methyl Ether → 2,4-Bis-(Cbz-valinyl-amino)-1,5-diphenyl-3-((methoxy)methoxy)pentane

HRID 847623Notes

Reaction equation

HRID 847623 reaction equation
[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].C(N(C(C)C)C(C)C)C.[CH3:64][O:65][CH2:66]Cl>ClCCl>[C:40]([NH:39][C@H:38]([C:37]([NH:36][CH:28]([CH:27]([O:54][CH2:64][O:65][CH3:66])[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)[CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)=[O:53])[CH:50]([CH3:52])[CH3:51])([O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:41]

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 3011026benzyl N-[(1S)-1-[[1-benzyl-3-[[(2S)-2-(benzyloxycarbonylamino)-3-methyl-butanoyl]amino]-2-hydroxy-4-phenyl-butyl]carbamoyl]-2-methyl-propyl]carbamate

Product 1

HCID 228455562,4-Bis-(Cbz-valinyl-amino)-1,5-diphenyl-3-((methoxy)methoxy)pentaneYield 10%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 22 mg of the resultant compound of Example 70 in 1 ml of dichloromethane was treated with 0.07 ml of ethyldiisopropylamine and 0.03 ml of chloromethyl methyl ether. The resulting solution was heated at reflux for 1 h. The cooled solution was concentrated in vacuo to give 26 mg of a crude solid which was recrystallized from ethyl acetate/chloroform to provide 15 mg of the desired compound (Rf 0.6, 10% methanol in chloroform) as a white solid, m.p. 197°-198° C. Mass spectrum: (M+H)+ =781.

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureat reflux for 1 h
  3. concentrationThe cooled solution was concentrated in vacuo
  4. customto give 26 mg of a crude solid which
  5. customwas recrystallized from ethyl acetate/chloroform

Sources & evidence

ORD record
ord-b677d80e5d9f4896b8482112b3122638
Source dataset
uspto-grants-1992_08
Patent number
US05142056

Reaction notes

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