Diethylenetriamine → Tert-butyl 4-(3,12-dioxo-1,4,7,10-tetraazacyclododecan-2-yl)butylcarbamate

HRID 241240

Reaction equation

HRID 241240 reaction equation
[NH2:1][C@H:2]([C:15]([O:17]C)=O)[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].Br[CH2:20][C:21]([O:23]C)=O.[NH2:25][CH2:26][CH2:27][NH:28][CH2:29][CH2:30][NH2:31]>>[O:17]=[C:15]1[NH:31][CH2:30][CH2:29][NH:28][CH2:27][CH2:26][NH:25][CH2:20][C:21](=[O:23])[NH:1][CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8](=[O:9])[O:10][C:11]([CH3:12])([CH3:13])[CH3:14]

Participants

4

Reactant 3

HCID 8111DiethylenetriamineHCID 60984Methyl bromoacetateHCID 7018776(S)-Methyl 2-amino-6-((tert-butoxycarbonyl)amino)hexanoate2×

Product 1

HCID 66809786Tert-butyl 4-(3,12-dioxo-1,4,7,10-tetraazacyclododecan-2-yl)butylcarbamate

Procedure

DOTA-alkyl-biotin was synthesized following the procedure of Takenouchi et al. (J. Organic Chem. 58:1955-1958, 1993) starting with the compound H-Lys(Boc)-OMe (Bachem, E-1620). H-Lys(Boc)-OMe was treated stepwise with methyl bromoacetate and diethylenetriamine to obtain tert-butyl 4-(3,12-dioxo-1,4,7,10-tetraazacyclododecan-2-yl)butylcarbamate. Borane-THF complex was used to reduce the carboxylic amides followed by trifluoroacetic acid Boc deprotection to obtain 4-(1,4,7,10-tetraazacyclododecan-2-yl)butan-1-amine. This compound was subsequently reacted with biotin-xx, SSE (Invitrogen, B-6352) in DMSO with a 10 fold molar excess of triethylamine for 3 hours vortexing at room temperature. In all synthesis steps compounds were purified by HPLC and confirmed by mass spectrometry with a Waters (Milford, Mass.) LCT electrospray time-of-flight (ES-TOF) liquid chromatography mass spectrometry (LC/MS) or by MALDI-TOF as described above.

Sources & evidence

ORD record
ord-8f0c53e84e694074b50de58fa5e5ba08
Source dataset
uspto-grants-2014_02
Patent number
US08648176B2

Linked notes

Loading…