HATU
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IUPAC name
1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate
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Identifiers | |
3D model (
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ChemSpider | |
ECHA InfoCard
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100.103.434 |
PubChem CID
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UNII | |
CompTox Dashboard (EPA)
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Properties | |
C10H15F6N6OP | |
Molar mass | 380.235 g·mol−1 |
Appearance | White crystalline solid |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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HATU (Hexafluorophosphate Azabenzotriazole Tetramethyl Uronium) is a
History
HATU was first reported by Louis A. Carpino in 1993 as an efficient means of preparing active esters derived from
Reactions
HATU is commonly encountered in amine acylation reactions (i.e., amide formation). Such reactions are typically performed in two distinct reaction steps: (1) reaction of a carboxylic acid with HATU to form the OAt-active ester; then (2) addition of the nucleophile (amine) to the active ester solution to afford the acylated product.
The reaction mechanism of carboxylic acid activation by HATU and subsequent N-acylation is summarised in the figure below. The mechanism is shown using the more commonly encountered and commercially available iminium isomer; a similar mechanism, however, is likely to apply to the uronium form. In the first step, the carboxylate anion (formed by deprotonation by an organic base [not shown]) attacks HATU to form the unstable O-acyl(tetramethyl)isouronium salt. The OAt anion rapidly attacks the isouronium salt, affording the OAt-active ester and liberating a stoichiometric quantity of tetramethylurea. Addition of a nucleophile, such as an amine, to the OAt-active ester results in acylation.
The high coupling efficiencies and fast reaction rates associated with HATU coupling are thought to arise from a neighbouring group effect brought about by the pyridine nitrogen atom, which stabilises the incoming amine through a hydrogen-bonded 7-membered cyclic transition state.[4]
Because of the extraordinary coupling efficiency of HATU, it has often been used for intramolecular amidation (coupling of a carboxylic acid and an amine of the same molecule). For example, the formation of cyclo-tetrapeptides through the head-to-tail reaction of linear tetrapeptides assisted by HATU has been reported.[5]
References
- ^ "Amine to Amide (Coupling) - HATU".
- .
- PMID 12491372.
- PMID 10930256.
- ISSN 1364-548X.