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 1052317ノート

反応式

HRID 1052317 の反応式
[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]

参加物

8

反応物 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

生成物 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収率 13.7%

試薬・触媒・溶媒 5

HCID 23978Copper触媒HCID 24462Copper Sulfate触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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)′.

後処理

  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

出典と根拠

ORDレコード
ord-e890600e06ac4871b3dcf179c0bf188b
出典データセット
uspto-grants-2016_07
特許番号
US09388144B2

反応ノート

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