1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (19S,23 S)-tri-tert-butyl 1-(1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-2-((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)-13,21-dioxo-2,14,20,22-tetraazapentacosane-19,23,25-tricarboxylate

HRID 1855268Notes

Reaction equation

HRID 1855268 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:100])[CH2:41][N:42]([CH2:92][C:93](=[O:99])[O:94][C:95]([CH3:98])([CH3:97])[CH3:96])[C:43](=[O:91])[CH2:44][N:45]1[CH:49]=[CH:48][N:47]=[C:46]1[CH2:50][N:51]([CH2:65][C:66]1[N:67]([CH2:71][C:72](=[O:90])[N:73]([CH2:82][C:83](=[O:89])[O:84][C:85]([CH3:88])([CH3:87])[CH3:86])[CH2:74][C:75](=[O:81])[O:76][C:77]([CH3:80])([CH3:79])[CH3:78])[CH:68]=[CH:69][N:70]=1)[CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][C:62](O)=[O:63])([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>C(Cl)Cl>[C:85]([O:84][C:83](=[O:89])[CH2:82][N:73]([CH2:74][C:75](=[O:81])[O:76][C:77]([CH3:80])([CH3:79])[CH3:78])[C:72](=[O:90])[CH2:71][N:67]1[CH:68]=[CH:69][N:70]=[C:66]1[CH2:65][N:51]([CH2:50][C:46]1[N:45]([CH2:44][C:43]([N:42]([CH2:92][C:93]([O:94][C:95]([CH3:97])([CH3:96])[CH3:98])=[O:99])[CH2:41][C:40](=[O:100])[O:39][C:35]([CH3:38])([CH3:36])[CH3:37])=[O:91])[CH:49]=[CH:48][N:47]=1)[CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][C:62](=[O:63])[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])([CH3:86])([CH3:87])[CH3:88]

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 7156164611-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)undecanoic acid

Product 1

HCID 59404243(19S,23 S)-tri-tert-butyl 1-(1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-2-((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)-13,21-dioxo-2,14,20,22-tetraazapentacosane-19,23,25-tricarboxylateYield 21.3%

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 (85 mg, 0.174 mmol), 11-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)undecanoic acid (118 mg, 0.127 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 overnight. The reaction mixture was purified by biotage eluting with 1% to 10% MeOH in DCM to afford (19S,23S)-tri-tert-butyl 1-(1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-2-((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)-13,21-dioxo-2,14,20,22-tetraazapentacosane-19,23,25-tricarboxylate (38 mg, 21%) as a colorless oil. 1H NMR (400 MHz, CDCl3) 6.95 (d, J=1.2 Hz, 2H), 6.83 (d, J=0.80 Hz, 2H), 5.97 (s, 1H), 5.28 (d, J=7.6 Hz, 1H), 5.23 (d, J=8.4 Hz, 1H), 4.94 (s, 4H), 4.33-4.25 (m, 2H), 4.12 (s, 4H), 4.03 (s, 4H), 3.63 (s, 4H), 3.25-3.16 (m, 2H), 2.53 (t, J=7.4 Hz, 2H), 2.33-2.24 (m, 2H), 2.15 (t, J=7.6 Hz, 2H), 2.08-2.03 (m, 2H), 2.02-1.20 (m, 85H); MS (ESI), 701.6 (M/2+H)+.

Workup

  1. customThe reaction mixture was purified by biotage
  2. washeluting with 1% to 10% MeOH in DCM

Sources & evidence

ORD record
ord-a7bf56bfe78e4d309aa6b76473de695d
Source dataset
uspto-grants-2015_02
Patent number
US08962799B2

Reaction notes

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