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-(tert-butoxy)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate

HRID 1422513Notes

Reaction equation

HRID 1422513 reaction equation
[C:1]([O:5][C:6](=[O:67])[CH2:7][N:8]1[CH:12]=[CH:11][N:10]=[C:9]1[CH2:13][N:14]([CH2:56][C:57]1[CH:62]=[CH:61][C:60]([O:63][CH2:64][C:65]#[CH:66])=[CH:59][CH:58]=1)[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20](=[O:55])[NH:21][CH2:22][CH2:23][CH2:24][CH2:25][C@@H:26]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[NH:27][C:28](=[O:47])[NH:29][C@H:30]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:31][CH2:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])([CH3:4])([CH3:3])[CH3:2].[N:68]([CH2:71][CH2:72][CH2:73][NH2:74])=[N+:69]=[N-:70]>C1COCC1.O.C(Cl)Cl.[Cu].[O-]S([O-])(=O)=O.[Cu+2]>[NH2:74][CH2:73][CH2:72][CH2:71][N:68]1[CH:66]=[C:65]([CH2:64][O:63][C:60]2[CH:61]=[CH:62][C:57]([CH2:56][N:14]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20](=[O:55])[NH:21][CH2:22][CH2:23][CH2:24][CH2:25][C@@H:26]([C:48]([O:50][C:51]([CH3:52])([CH3:53])[CH3:54])=[O:49])[NH:27][C:28](=[O:47])[NH:29][C@H:30]([C:40]([O:42][C:43]([CH3:44])([CH3:45])[CH3:46])=[O:41])[CH2:31][CH2:32][C:33]([O:35][C:36]([CH3:38])([CH3:39])[CH3:37])=[O:34])[CH2:13][C:9]3[N:8]([CH2:7][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:67])[CH:12]=[CH:11][N:10]=3)=[CH:58][CH:59]=2)[N:70]=[N:69]1

Participants

8

Reactant 2

HCID 1501103-Azidopropan-1-amineHCID 86676477(14S,18S)-tri-tert-butyl 1-(1-(2-(tert-butoxy)-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 86676478(14S,18S)-tri-tert-butyl 2-(4-((1-(3-aminopropyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl)-1-(1-(2-(tert-butoxy)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylateYield 57.2%

Reagents, catalysts & solvents 5

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

Procedure

To a solution of (14S,18S)-tri-tert-butyl 1-(1-(2-(tert-butoxy)-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 (250 mg, 0.266 mmol) and 3-azidopropan-1-amine (200 mg, 2.0 mmol) in THF (5.0 mL) and water (1.0 mL) was added copper powder (17 mg) and 1 N CuSO4 (0.05 mL). The mixture was stirred at room temperature for 6 hrs under nitrogen, diluted with DCM, washed with 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-(tert-butoxy)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (158 mg, 57%) as a yellow oil. MS (ESI), 520.4 (M/2-41)+.

Workup

  1. washwashed with 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-421d778e6bc7449aa722e32df36f18fb
Source dataset
uspto-grants-2015_01
Patent number
US08926944B2

Reaction notes

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