N-[N-[N-[N-[N-[3-(tert-butoxycarbonyl)propionyl]-O-tert-butyl-L-alpha-aspartyl]-O-tert-butyl-L-alpha-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucine benzyl ester → N-[N-[N-[N-[N-[3-(tert-butoxycarbonyl)propionyl]-O-tert-butyl-L-alpha-aspartyl]-O-tert-butyl-L-alpha-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucine

HRID 362124Notes

Reaction equation

HRID 362124 reaction equation
C([O:8][C:9](=[O:72])[C@H:10]([CH2:68][CH:69]([CH3:71])[CH3:70])[NH:11][C:12](=[O:67])[C@H:13]([C:63]([CH3:66])([CH3:65])[CH3:64])[NH:14][C:15](=[O:62])[C@H:16]([CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=1[CH3:61])[NH:17][C:18](=[O:53])[C@H:19]([CH2:44][CH2:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[NH:20][C:21](=[O:43])[C@H:22]([CH2:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[NH:23][C:24](=[O:34])[CH2:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])C1C=CC=CC=1>CN(C)C=O.[Pd]>[C:30]([O:29][C:27]([CH2:26][CH2:25][C:24]([NH:23][C@H:22]([C:21]([NH:20][C@H:19]([C:18]([NH:17][C@H:16]([C:15]([NH:14][C@H:13]([C:12]([NH:11][C@H:10]([C:9]([OH:72])=[O:8])[CH2:68][CH:69]([CH3:70])[CH3:71])=[O:67])[C:63]([CH3:66])([CH3:65])[CH3:64])=[O:62])[CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=1[CH3:61])=[O:53])[CH2:44][CH2:45][C:46](=[O:52])[O:47][C:48]([CH3:49])([CH3:50])[CH3:51])=[O:43])[CH2:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:34])=[O:28])([CH3:31])([CH3:33])[CH3:32]

Participants

4

Reactant 1

HCID 22942120N-[N-[N-[N-[N-[3-(tert-butoxycarbonyl)propionyl]-O-tert-butyl-L-alpha-aspartyl]-O-tert-butyl-L-alpha-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucine benzyl ester

Product 1

HCID 22942121N-[N-[N-[N-[N-[3-(tert-butoxycarbonyl)propionyl]-O-tert-butyl-L-alpha-aspartyl]-O-tert-butyl-L-alpha-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucineYield 96.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 6.8 g (6.75 mmol) of N-[N-[N-[N-[N-[3-(tert-butoxycarbonyl)propionyl]-O-tert-butyl-L-α-aspartyl]-O-tert-butyl-L-α-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucine benzyl ester in 200 ml of dimethylformamide was hydrogenated over 600 mg of 10% palladium/carbon for 1 hour. The catalyst was removed by filtration and the filtrate was evaporated to give 15 g of crude product which was chromatographed on silica gel using 10-15% methanol in dichloromethane for the elution to give 6 g of N-[N-[N-[N-[N-[3-(tert-butoxycarbonyl)propionyl]-O-tert-butyl-L-α-aspartyl]-O-tert-butyl-L-α-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucine as a white solid of melting point 235°-236° C.; MS: m/e 918.4 [M+H]+, m/e 940.3 [M+Na]+.

Workup

  1. customThe catalyst was removed by filtration
  2. customthe filtrate was evaporated
  3. customto give 15 g of crude product which
  4. customwas chromatographed on silica gel using 10-15% methanol in dichloromethane for the elution

Sources & evidence

ORD record
ord-e7688b1303014b58b72d19743f095a0c
Source dataset
uspto-grants-1999_02
Patent number
US05866684

Reaction notes

Loading…