Diisopropylethylamine → (2S,7S,11S)-2-(4-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)butyl)-7,11-bis(tert-butoxycarbonyl)-16,16-dimethyl-4,9,14-trioxo-15-oxa-3,8,10-triazaheptadecan-1-oic acid

HRID 1043386Notes

Reaction equation

HRID 1043386 reaction equation
[C:1]([O:5][C:6](=[O:41])[C@@H:7]([NH:20][C:21](=[O:40])[NH:22][C@@H:23]([CH2:31][CH2:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:8][CH2:9][C:10](ON1C(=O)CCC1=O)=[O:11])([CH3:4])([CH3:3])[CH3:2].[NH2:42][C@@H:43]([CH2:47][CH2:48][CH2:49][CH2:50][N:51]([CH2:78][C:79]1[N:80]([CH2:84][C:85]([N:87]([CH2:96][C:97]([O:99][C:100]([CH3:103])([CH3:102])[CH3:101])=[O:98])[CH2:88][C:89](=[O:95])[O:90][C:91]([CH3:94])([CH3:93])[CH3:92])=[O:86])[CH:81]=[CH:82][N:83]=1)[CH2:52][C:53]1[N:54]([CH2:58][C:59](=[O:77])[N:60]([CH2:69][C:70](=[O:76])[O:71][C:72]([CH3:75])([CH3:74])[CH3:73])[CH2:61][C:62](=[O:68])[O:63][C:64]([CH3:67])([CH3:66])[CH3:65])[CH:55]=[CH:56][N:57]=1)[C:44]([OH:46])=[O:45].CCN(C(C)C)C(C)C>CN(C=O)C>[C:100]([O:99][C:97](=[O:98])[CH2:96][N:87]([CH2:88][C:89](=[O:95])[O:90][C:91]([CH3:94])([CH3:93])[CH3:92])[C:85](=[O:86])[CH2:84][N:80]1[CH:81]=[CH:82][N:83]=[C:79]1[CH2:78][N:51]([CH2:52][C:53]1[N:54]([CH2:58][C:59](=[O:77])[N:60]([CH2:69][C:70](=[O:76])[O:71][C:72]([CH3:75])([CH3:74])[CH3:73])[CH2:61][C:62](=[O:68])[O:63][C:64]([CH3:65])([CH3:67])[CH3:66])[CH:55]=[CH:56][N:57]=1)[CH2:50][CH2:49][CH2:48][CH2:47][C@H:43]([NH:42][C:10](=[O:11])[CH2:9][CH2:8][C@@H:7]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:41])[NH:20][C:21](=[O:40])[NH:22][C@H:23]([C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])[CH2:31][CH2:32][C:33](=[O:34])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C:44]([OH:46])=[O:45])([CH3:103])([CH3:102])[CH3:101]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 59404242Glu-urea-Glu-NHS esterHCID 67144679(S)-2-amino-6-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)hexanoic acid

Product 1

HCID 59408723(2S,7S,11S)-2-(4-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)butyl)-7,11-bis(tert-butoxycarbonyl)-16,16-dimethyl-4,9,14-trioxo-15-oxa-3,8,10-triazaheptadecan-1-oic acidYield 84.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (S)-di-tert-butyl 2-(3-((S)-1-tert-butoxy-5-(2,5-dioxopyrrolidin-1-yloxy)-1,5-dioxopentan-2-yl)ureido)pentanedioate (82 mg, 0.14 mmol), ((S)-2-amino-6-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)hexanoic acid (98 mg, 0.11 mmol) and DIPEA (0.50 mL) in DMF (2.0 mL) was stirred at rt for overnight. The Solvent was removed under reduced pressure to give a residue, which was purified by biotage eluting with 1% to 40% MeOH in DCM to afford (2S,7S,11S)-2-(4-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)butyl)-7,11-bis(tert-butoxycarbonyl)-16,16-dimethyl-4,9,14-trioxo-15-oxa-3,8,10-triazaheptadecan-1-oic acid (125 mg, 84%) as a white solid. MS (ESI), 674.6 (M/2+H)+.

Workup

  1. customThe Solvent was removed under reduced pressure
  2. customto give a residue, which
  3. customwas purified by biotage
  4. washeluting with 1% to 40% MeOH in DCM

Sources & evidence

ORD record
ord-136d8f65f2dd49d5957be8ba15c1144f
Source dataset
uspto-grants-2013_10
Patent number
US08562945B2

Reaction notes

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