1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (5S,12S,16S)-tri-tert-butyl 5-(4-(bis((1-(2-(bis(2-tert-butoxy-2-oxo ethyl)amino)-2-oxo ethyl)-1H-imidazol-2-yl)methyl)amino)butyl)-1-(9H-fluoren-9-yl)-3,6,14-trioxo-2-oxa-4,7,13,15-tetraazaoctadecane-12,16,18-tricarboxylate

HRID 56330Notes

Reaction equation

HRID 56330 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C@H:6]([NH:14][C:15](=[O:34])[NH:16][C@@H:17]([CH2:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[CH:35]1[C:47]2[CH:46]([CH2:48][O:49][C:50]([NH:52][CH:53]([CH2:57][CH2:58][CH2:59][CH2:60][N:61]([CH2:88][C:89]3[N:90]([CH2:94][C:95]([N:97]([CH2:106][C:107]([O:109][C:110]([CH3:113])([CH3:112])[CH3:111])=[O:108])[CH2:98][C:99](=[O:105])[O:100][C:101]([CH3:104])([CH3:103])[CH3:102])=[O:96])[CH:91]=[CH:92][N:93]=3)[CH2:62][C:63]3[N:64]([CH2:68][C:69](=[O:87])[N:70]([CH2:79][C:80](=[O:86])[O:81][C:82]([CH3:85])([CH3:84])[CH3:83])[CH2:71][C:72](=[O:78])[O:73][C:74]([CH3:77])([CH3:76])[CH3:75])[CH:65]=[CH:66][N:67]=3)[C:54](O)=[O:55])=[O:51])[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[C:39]=2[CH:38]=[CH:37][CH:36]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:110]([O:109][C:107](=[O:108])[CH2:106][N:97]([CH2:98][C:99](=[O:105])[O:100][C:101]([CH3:104])([CH3:103])[CH3:102])[C:95](=[O:96])[CH2:94][N:90]1[CH:91]=[CH:92][N:93]=[C:89]1[CH2:88][N:61]([CH2:62][C:63]1[N:64]([CH2:68][C:69](=[O:87])[N:70]([CH2:79][C:80](=[O:86])[O:81][C:82]([CH3:83])([CH3:84])[CH3:85])[CH2:71][C:72](=[O:78])[O:73][C:74]([CH3:75])([CH3:76])[CH3:77])[CH:65]=[CH:66][N:67]=1)[CH2:60][CH2:59][CH2:58][CH2:57][C@@H:53]([C:54](=[O:55])[NH:1][CH2:2][CH2:3][CH2:4][CH2:5][C@@H:6]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[NH:14][C:15](=[O:34])[NH:16][C@H:17]([C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])[CH2:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[NH:52][C:50](=[O:51])[O:49][CH2:48][CH:46]1[C:45]2[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=2[C:39]2[C:47]1=[CH:35][CH:36]=[CH:37][CH:38]=2)([CH3:111])([CH3:112])[CH3:113]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 251942251,5-Bis(1,1-dimethylethyl) N-((((1S)-5-amino-1-((1,1-dimethylethoxy)carbonyl)pentyl)amino)carbonyl)-L-glutamateHCID 781127812-(((9H-fluoren-9-yl)methoxy)carbonylamino)-6-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)hexanoic acid

Product 1

HCID 86643307(5S,12S,16S)-tri-tert-butyl 5-(4-(bis((1-(2-(bis(2-tert-butoxy-2-oxo ethyl)amino)-2-oxo ethyl)-1H-imidazol-2-yl)methyl)amino)butyl)-1-(9H-fluoren-9-yl)-3,6,14-trioxo-2-oxa-4,7,13,15-tetraazaoctadecane-12,16,18-tricarboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-di-tert-butyl 2-(3-((S)-6-amino-1-tert-butoxy-1-oxohexan-2-yl)ureido)pentanedioate (97 mg, 0.20 mmol), 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-6-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)hexanoic acid (132 mg, 0.12 mmol), EDCI (38 mg, 0.20 mmol), HOBt (26 mg, 0.20) and DIPEA (0.30 mL) in DCM (5.0 mL) was stirred at rt for 2 days. The reaction mixture was purified by biotage eluting with 1% MeOH in DCM to afford (5S,12S,16S)-tri-tert-butyl 5-(4-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)butyl)-1-(9H-fluoren-9-yl)-3,6,14-trioxo-2-oxa-4,7,13,15-tetraazaoctadecane-12,16,18-tricarboxylate (impure) as an oil.

Workup

  1. customThe reaction mixture was purified by biotage
  2. washeluting with 1% MeOH in DCM

Sources & evidence

ORD record
ord-903e6a7fc0cd4f11bfc496aef4c4f938
Source dataset
uspto-grants-2016_09
Patent number
US09433594B2

Reaction notes

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