(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-((1-(3-(2-(4,7,10-tris(2-(tert-butoxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)acetamido)propyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl)-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate → (14S,18S)-1-(1-(2-(bis(carboxymethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2-(4-((1-(3-(2-(4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl)acetamido)propyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl)-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylic acid

HRID 1052318Notes

Reaction equation

HRID 1052318 reaction equation
C([O:5][C:6](=[O:125])[CH2:7][N:8]([CH2:117][C:118](=[O:124])[O:119]C(C)(C)C)[C:9](=[O:116])[CH2:10][N:11]1[CH:15]=[CH:14][N:13]=[C:12]1[CH2:16][N:17]([CH2:59][C:60]1[CH:65]=[CH:64][C:63]([O:66][CH2:67][C:68]2[N:69]=[N:70][N:71]([CH2:73][CH2:74][CH2:75][NH:76][C:77](=[O:115])[CH2:78][N:79]3[CH2:90][CH2:89][N:88]([CH2:91][C:92](=[O:98])[O:93]C(C)(C)C)[CH2:87][CH2:86][N:85]([CH2:99][C:100](=[O:106])[O:101]C(C)(C)C)[CH2:84][CH2:83][N:82]([CH2:107][C:108]([O:110]C(C)(C)C)=[O:109])[CH2:81][CH2:80]3)[CH:72]=2)=[CH:62][CH:61]=1)[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23](=[O:58])[NH:24][CH2:25][CH2:26][CH2:27][CH2:28][C@@H:29]([C:51]([O:53]C(C)(C)C)=[O:52])[NH:30][C:31](=[O:50])[NH:32][C@H:33]([C:43]([O:45]C(C)(C)C)=[O:44])[CH2:34][CH2:35][C:36]([O:38]C(C)(C)C)=[O:37])(C)(C)C>C(O)(C(F)(F)F)=O.C(Cl)Cl>[C:118]([CH2:117][N:8]([CH2:7][C:6]([OH:125])=[O:5])[C:9](=[O:116])[CH2:10][N:11]1[CH:15]=[CH:14][N:13]=[C:12]1[CH2:16][N:17]([CH2:59][C:60]1[CH:61]=[CH:62][C:63]([O:66][CH2:67][C:68]2[N:69]=[N:70][N:71]([CH2:73][CH2:74][CH2:75][NH:76][C:77](=[O:115])[CH2:78][N:79]3[CH2:90][CH2:89][N:88]([CH2:91][C:92]([OH:98])=[O:93])[CH2:87][CH2:86][N:85]([CH2:99][C:100]([OH:106])=[O:101])[CH2:84][CH2:83][N:82]([CH2:107][C:108]([OH:110])=[O:109])[CH2:81][CH2:80]3)[CH:72]=2)=[CH:64][CH:65]=1)[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23](=[O:58])[NH:24][CH2:25][CH2:26][CH2:27][CH2:28][C@@H:29]([C:51]([OH:53])=[O:52])[NH:30][C:31](=[O:50])[NH:32][C@H:33]([C:43]([OH:45])=[O:44])[CH2:34][CH2:35][C:36]([OH:38])=[O:37])([OH:124])=[O:119]

Participants

4

Reactant 1

HCID 86676474(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-((1-(3-(2-(4,7,10-tris(2-(tert-butoxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)acetamido)propyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl)-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate

Product 1

HCID 86676475(14S,18S)-1-(1-(2-(bis(carboxymethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2-(4-((1-(3-(2-(4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl)acetamido)propyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl)-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylic acid

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of ((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-((1-(3-(2-(4,7,10-tris(2-(tert-butoxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)acetamido)propyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl)-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (21 mg, 0.012 mmol) in TFA (2.0 mL) and DCM (2.0 mL) was stirred at rt overnight. The solvent was removed under a stream of nitrogen to give a crude ((14S,18S)-1-(1-(2-(bis(carboxymethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2-(4-((1-(3-(2-(4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl)acetamido)propyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl)-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylic acid, (MIP-1459), which was dissolved in ammonium acetate (0.30 mL, 0.50 N) solution in water (0.50 mL) with InCl3 (10 mg). The reaction mixture was heated at 95° C. for 1 h and was purified by HPLC to give the product (MIP-1445, (1 mg)). MS (ESI), 714.9 (M/2+H)+.

Workup

  1. customThe solvent was removed under a stream of nitrogen

Sources & evidence

ORD record
ord-8970f0d4cb714b01a9beff0b36edb56a
Source dataset
uspto-grants-2016_07
Patent number
US09388144B2

Reaction notes

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