1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (14S,18S)-tri-tert-butyl 1-(1-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2-(4-(prop-2-yn-1-yloxy)benzyl)-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate

HRID 1052315Notes

Reaction equation

HRID 1052315 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].[C:35]([O:39][C:40](=[O:80])[CH2:41][N:42]([CH2:72][C:73](=[O:79])[O:74][C:75]([CH3:78])([CH3:77])[CH3:76])[C:43](=[O:71])[CH2:44][N:45]1[CH:49]=[CH:48][N:47]=[C:46]1[CH2:50][N:51]([CH2:60][C:61]1[CH:66]=[CH:65][C:64]([O:67][CH2:68][C:69]#[CH:70])=[CH:63][CH:62]=1)[CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][C:57](O)=[O:58])([CH3:38])([CH3:37])[CH3:36].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>ClCCCl>[C:75]([O:74][C:73](=[O:79])[CH2:72][N:42]([CH2:41][C:40](=[O:80])[O:39][C:35]([CH3:38])([CH3:37])[CH3:36])[C:43](=[O:71])[CH2:44][N:45]1[CH:49]=[CH:48][N:47]=[C:46]1[CH2:50][N:51]([CH2:60][C:61]1[CH:66]=[CH:65][C:64]([O:67][CH2:68][C:69]#[CH:70])=[CH:63][CH:62]=1)[CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][C:57](=[O:58])[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])([CH3:78])([CH3:76])[CH3:77]

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 894010636-(((1-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)(4-(prop-2-yn-1-yloxy)benzyl)amino)hexanoic acid

Product 1

HCID 86676473(14S,18S)-tri-tert-butyl 1-(1-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2-(4-(prop-2-yn-1-yloxy)benzyl)-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylateYield 77%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of (S)-di-tert-butyl 2-(3-((S)-6-amino-1-(tert-butoxy)-1-oxohexan-2-yl)ureido)pentanedioate (0.742 g, 1.52 mmol), 6-(((1-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)(4-(prop-2-yn-1-yloxy)benzyl)amino)hexanoic acid (0.244 g, 0.38 mmol), EDCI (0.290 g, 1.52 mmol), HOBt (0.051 g, 0.38 mmol) and DIPEA (0.40 mL) in DCE (5.0 mL) was stirred at room temperature for 4 h. The solvent was evaporated to give a residue, which was purified by Biotage SP4 eluting with DCM/MeOH to give (14S,18S)-tri-tert-butyl 1-(1-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2-(4-(prop-2-yn-1-yloxy)benzyl)-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (0.3237 g, 77%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 7.64 (t, J=5.4 Hz, 1H), 7.17 (d, J=8.4 Hz, 2H), 6.93 (s, 1H), 6.87 (d, J=8.8 Hz, 2H), 6.74 (s, 1H), 6.26 (d, J=8.4 Hz, 1H), 6.22 (d, J=8.0 Hz, 1H), 5.02 (s, 2H), 4.72 (d, J=2.0 Hz, 2H), 4.24 (s, 2H), 4.03-3.89 (m, 4H), 3.51 (t, J=2.0 Hz, 1H), 3.48 (s, 2H), 3.39 (s, 2H), 2.95 (q, J=6.3 Hz, 2H), 2.22-2.15 (m, 4H), 1.94 (t, J=7.4 Hz, 2H), 1.85-1.04 (m, 34H); MS (ESI), 1111.6 (M+H)+.

Workup

  1. customThe solvent was evaporated
  2. customto give a residue, which
  3. customwas purified by Biotage SP4
  4. washeluting with DCM/MeOH

Sources & evidence

ORD record
ord-f987547fa8584061859e5276cb2dad5d
Source dataset
uspto-grants-2016_07
Patent number
US09388144B2

Reaction notes

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