Azido-mono-amide-DOTA-tris(t-Bu ester) → (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

HRID 1422509Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1422509
[C:1]([O:5][C:6](=[O:79])[CH2:7][N:8]([CH2:71][C:72](=[O:78])[O:73][C:74]([CH3:77])([CH3:76])[CH3:75])[C:9](=[O:70])[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]#[CH:69])=[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:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[NH:30][C:31](=[O:50])[NH:32][C@H:33]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:34][CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])([CH3:4])([CH3:3])[CH3:2].[N:80]([CH2:83][CH2:84][CH2:85][NH:86][C:87](=[O:125])[CH2:88][N:89]1[CH2:100][CH2:99][N:98]([CH2:101][C:102]([O:104][C:105]([CH3:108])([CH3:107])[CH3:106])=[O:103])[CH2:97][CH2:96][N:95]([CH2:109][C:110]([O:112][C:113]([CH3:116])([CH3:115])[CH3:114])=[O:111])[CH2:94][CH2:93][N:92]([CH2:117][C:118]([O:120][C:121]([CH3:124])([CH3:123])[CH3:122])=[O:119])[CH2:91][CH2:90]1)=[N+:81]=[N-:82]>C1COCC1.O.CCOC(C)=O.[Cu].[O-]S([O-])(=O)=O.[Cu+2]>[C:74]([O:73][C:72](=[O:78])[CH2:71][N:8]([CH2:7][C:6](=[O:79])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[C:9](=[O:70])[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:82]=[N:81][N:80]([CH2:83][CH2:84][CH2:85][NH:86][C:87](=[O:125])[CH2:88][N:89]3[CH2:90][CH2:91][N:92]([CH2:117][C:118](=[O:119])[O:120][C:121]([CH3:122])([CH3:123])[CH3:124])[CH2:93][CH2:94][N:95]([CH2:109][C:110](=[O:111])[O:112][C:113]([CH3:115])([CH3:116])[CH3:114])[CH2:96][CH2:97][N:98]([CH2:101][C:102]([O:104][C:105]([CH3:108])([CH3:107])[CH3:106])=[O:103])[CH2:99][CH2:100]3)[CH:69]=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]([O:53][C:54]([CH3:55])([CH3:56])[CH3:57])=[O:52])[NH:30][C:31](=[O:50])[NH:32][C@H:33]([C:43]([O:45][C:46]([CH3:47])([CH3:48])[CH3:49])=[O:44])[CH2:34][CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])([CH3:77])([CH3:76])[CH3:75]

Komponenten

8

Edukt 2

HCID 59487518Azido-mono-amide-DOTA-tris(t-Bu ester)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-tricarboxylate

Produkt 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-tricarboxylateAusbeute 13,7 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 23978CopperKatalysatorHCID 24462Copper SulfateKatalysatorHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To 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-(prop-2-yn-1-yloxy)benzyl)-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (145 mg, 0.13 mmol), tri-tert-butyl 2,2′,2″-(10-(2-((3-azidopropyl)amino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate (59 mg, 0.090 mmol) in THF (5.0 mL) and water (1.0 mL) was added copper powder (6.4 mg) and 1 N CuSO4 (0.01 mL). The mixture was stirred at room temperature for overnight under nitrogen, diluted with EtOAc, washed with an aqueous saturated solution of EDTA. The solvent was evaporated under reduce pressure to afford a residue, which was purified by Biotage SP4 to afford ((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 (21.8 mg). MS (ESI), 883.2 (M/2+H)+.

Aufarbeitung

  1. washwashed with an aqueous saturated solution of EDTA
  2. customThe solvent was evaporated
  3. customto afford a residue, which
  4. customwas purified by Biotage SP4

Quellen und Nachweise

ORD-Eintrag
ord-81b028fe366c4ec18986c55e646a7da7
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08926944B2

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