Diisopropylethylamine → (7S,11 S,26S)-26-(4-(bis((1-(2-tert-butoxy-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)butyl)-7,11-bis(tert-butoxycarbonyl)-2,2-dimethyl-4,9,17,24-tetraoxo-3-oxa-8,10,16,25-tetraazaheptacosan-27-oic acid

HRID 56340Notes

Reaction equation

HRID 56340 reaction equation
[C:1]([O:5][C:6](=[O:52])[C@@H:7]([NH:31][C:32](=[O:51])[NH:33][C@@H:34]([CH2:42][CH2:43][C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:8][CH2:9][CH2:10][CH2:11][NH:12][C:13](=[O:30])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20](ON1C(=O)CCC1=O)=[O:21])([CH3:4])([CH3:3])[CH3:2].[NH2:53][C@@H:54]([CH2:58][CH2:59][CH2:60][CH2:61][N:62]([CH2:77][C:78]1[N:79]([CH2:83][C:84]([O:86][C:87]([CH3:90])([CH3:89])[CH3:88])=[O:85])[CH:80]=[CH:81][N:82]=1)[CH2:63][C:64]1[N:65]([CH2:69][C:70](=[O:76])[O:71][C:72]([CH3:75])([CH3:74])[CH3:73])[CH:66]=[CH:67][N:68]=1)[C:55]([OH:57])=[O:56].CCN(C(C)C)C(C)C>CN(C=O)C>[C:72]([O:71][C:70](=[O:76])[CH2:69][N:65]1[CH:66]=[CH:67][N:68]=[C:64]1[CH2:63][N:62]([CH2:77][C:78]1[N:79]([CH2:83][C:84](=[O:85])[O:86][C:87]([CH3:90])([CH3:89])[CH3:88])[CH:80]=[CH:81][N:82]=1)[CH2:61][CH2:60][CH2:59][CH2:58][C@@H:54]([C:55]([OH:57])=[O:56])[NH:53][C:20](=[O:21])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][C:13](=[O:30])[NH:12][CH2:11][CH2:10][CH2:9][CH2:8][C@@H:7]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:52])[NH:31][C:32](=[O:51])[NH:33][C@H:34]([C:35]([O:37][C:38]([CH3:39])([CH3:40])[CH3:41])=[O:36])[CH2:42][CH2:43][C:44](=[O:45])[O:46][C:47]([CH3:49])([CH3:50])[CH3:48])([CH3:73])([CH3:75])[CH3:74]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 59408652(S)-2-amino-6-(bis((1-(2-tert-butoxy-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)hexanoic acidHCID 86643493(S)-di-tert-butyl 2-(3-((S)-1-tert-butoxy-6-(8-(2,5-dioxopyrrolidin-1-yloxy)-8-oxooctanamido)-1-oxohexan-2-yl)ureido)pentanedioate

Product 1

HCID 86762746(7S,11 S,26S)-26-(4-(bis((1-(2-tert-butoxy-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)butyl)-7,11-bis(tert-butoxycarbonyl)-2,2-dimethyl-4,9,17,24-tetraoxo-3-oxa-8,10,16,25-tetraazaheptacosan-27-oic acidYield 22.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (S)-di-tert-butyl 2-(3-((S)-1-tert-butoxy-6-(8-(2,5-dioxopyrrolidin-1-yloxy)-8-oxooctanamido)-1-oxohexan-2-yl)ureido)pentanedioate (0.291 g, 0.45 mmol), (S)-2-amino-6-(bis((1-(2-tert-butoxy-2-oxoethyl)-1H-imidazol-2-yl)methyl) amino)hexanoic acid (0.22 g, 0.412 mmol) and DIPEA (1.0 mL) in DMF (4.0 mL) was stirred at room temperature for overnight. The solvent was evaporated to give a residue, which was purified by Biotage eluting with DCM/MeOH to give (7S,11S,26S)-26-(4-(bis((1-(2-tert-butoxy-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)butyl)-7,11-bis(tert-butoxycarbonyl)-2,2-dimethyl-4,9,17,24-tetraoxo-3-oxa-8,10,16,25-tetraazaheptacosan-27-oic acid (0.1089 g, 21%). MS (ESI), 581 (M/2+H)+.

Workup

  1. customThe solvent was evaporated
  2. customto give a residue, which
  3. customwas purified by Biotage
  4. washeluting with DCM/MeOH

Sources & evidence

ORD record
ord-92707de6019544dbbb61c8d5c7a03bb3
Source dataset
uspto-grants-2016_09
Patent number
US09433594B2

Reaction notes

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