3-Azidopropan-1-amine → (14S,18S)-tri-tert-butyl 2-(4-((1-(3-aminopropyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl)-1-(1-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate

HRID 1422508Notes

Reaction equation

HRID 1422508 reaction equation
[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][NH2:86])=[N+:81]=[N-:82]>C1COCC1.O.C(Cl)Cl.[Cu].[O-]S([O-])(=O)=O.[Cu+2]>[NH2:86][CH2:85][CH2:84][CH2:83][N:80]1[CH:69]=[C:68]([CH2:67][O:66][C:63]2[CH:62]=[CH:61][C:60]([CH2:59][N:17]([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])[CH2:16][C:12]3[N:11]([CH2:10][C:9]([N:8]([CH2:7][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:79])[CH2:71][C:72](=[O:78])[O:73][C:74]([CH3:77])([CH3:76])[CH3:75])=[O:70])[CH:15]=[CH:14][N:13]=3)=[CH:65][CH:64]=2)[N:82]=[N:81]1

Participants

8

Reactant 2

HCID 1501103-Azidopropan-1-amineHCID 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

Product 1

HCID 86676472(14S,18S)-tri-tert-butyl 2-(4-((1-(3-aminopropyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl)-1-(1-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylateYield 25%

Reagents, catalysts & solvents 5

HCID 23978CopperCatalystHCID 24462Copper SulfateCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

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 (65 mg, 0.0586 mmol) and 3-azidopropan-1-amine (200 mg, 2.0 mmol) in THF (2.0 mL) and water (0.5 mL) was added copper powder (10 mg) and 1 N CuSO4 (0.05 mL). The mixture was stirred at room temperature for 2 h under nitrogen, diluted with DCM and 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 2-(4-((1-(3-aminopropyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl)-1-(1-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (17.5 mg, 25%). MS (ESI), 605.8 (M/2+H)+.

Workup

  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

Sources & evidence

ORD record
ord-a84cdfbcb4044e6b922b275c4218efe1
Source dataset
uspto-grants-2015_01
Patent number
US08926944B2

Reaction notes

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