HATU Chemical Properties

Melting point:

183-188 °C (dec.)

RTECS 

XZ5633000

storage temp. 

2-8°C

solubility 

>16mg/mL in DMSO

form 

powder to crystaline

color 

White to Almost white

Water Solubility 

Soluble in acetonitrile. Insoluble in water.

InChI

InChI=1S/C10H15N6O.F6P/c1-13(2)10(14(3)4)15-8-6-5-7-11-9(8)16(17)12-15;1-7(2,3,4,5)6/h5-7H,1-4H3;/q+1;-1

InChIKey

KZAWCZZRROLLDL-UHFFFAOYSA-N

SMILES

[P+5]([F-])([F-])([F-])([F-])([F-])[F-].C(=[N+]1/N=N(=O)C2=NC=CC=C/12)(\N(C)C)/N(C)C

CAS DataBase Reference

148893-10-1(CAS DataBase Reference)

EPA Substance Registry System

1H-1,2,3-Triazolo[4,5-b]pyridinium, 1-[bis(dimethylamino)methylene]-, hexafluorophosphate(1-), 3-oxide (148893-10-1)

Safety Information

Hazard Codes 

Xi,Xn,E

Risk Statements 

36/37/38-20/21/22-2

Safety Statements 

26-37/39-36/37-36-35

RIDADR 

1325

WGK Germany 

3

F 

10-21

HazardClass 

4.1

PackingGroup 

Ⅱ

HS Code 

29339999

MSDS

• Language:English Provider:SigmaAldrich

HATU Usage And Synthesis

Description

HATU, first prepared by Louis A. Carpino in 1993, is widely used in carboxylic acid amidation reactions. It acts as a facilitator of amide bond generation by activating the carboxyl group.

Chemical Properties

White crystalline to off-white powder

Uses

HATU[148893-10-1] is a coupling reagent and used as an additive in peptide synthesis. It is also involved efficiently to speed up the coupling process and reduces the loss of chiral integrity.
Reagent for: Synthesis of Aurora A kinase inhibitors, HPLC assay to determine D- and L- acid enantiomers in human plasma, Amide bond formation reactions.
Catalyst for: Selective acylation, Selecocyclization-oxidation deselenation sequence.

Reactions

HATU is a very promising coupling agent for chemical protein synthesis.

This strategy was exploited to prepare macrocycles from the trimeric linear arylopeptoids (ortho-, meta-, and para-) containing isopropyl or ethyl side chains, synthesized as described by Hjelmgaard et al. The cyclization procedure reported for α,β-cyclopeptoids was applied. The linear arylopeptoids were cyclized in the presence of HATU and DIPEA in CH?Cl?/DMF (4:1) after the deprotection of the tert-butyl group in TFA/CH?Cl?.

After the synthesis of the Fmoc-protected monomers, the oligomers were synthesized on the 2-chlorotrityl resin with excellent yield of coupling (>98%). The trimers and tetramers of the different isomers were synthesized in good overall yield (60-84%). Then, the crude oligomers were cyclized in DMF in the presence of HATU and DIPEA in high dilution (3 × 10?3 M) to furnish the cyclized trimers and tetramers in good yields ranging between 32% and 72%.

Synthesis

The synthesis of HATU is as follows:The resulting residue treated with 2-Methoxycarbonylamino-3-methyl-butyric acid (60 mg, 0.343 mmol) and HATU (130 mg, 0.343 mmol), suspended in DMF (3 mL) and cooled to 0° C. DIPEA (0.272 mL, 1.56 mmol) was added dropwise. After stirring for 4 h, NaOH (5M in H2O, 0.300 mL, 1.5 mmol) was added. This mixture was stirred for 3 h then diluted with EtOAc and washed with 1 M LiOH (2*) then brine. The organic phase was dried over MgSO4, filtered and concentrated. The crude residue was then purified by HPLC to afford the title compound (53 mg, 44%).

References

[1] CHAWLA P A, SHOME A, JHA K T. Hexafluorophosphate Azabenzotriazole Tetramethyl Uronium (HATU): A Unique Cross-Coupling Reagent[J]. SynOpen, 2023, 66 2: 0. DOI:10.1055/s-0042-1751499.
[2] LOUIS A. CARPINO. Comparison of the Effects of 5- and 6-HOAt on Model Peptide Coupling Reactions Relative to the Cases for the 4- and 7-Isomers?,?[J]. Organic Letters, 2000, 2 15: 2253-2256. DOI:10.1021/ol006013z.

HATU(148893-10-1)Related Product Information

• Ammonium hexafluorophosphate
• Potassium hexafluorophosphate
• Lithium hexafluorophosphate
• Ribavirin
• 1,2,4-Triazole
• 5-Methyl-1H-benzotriazole
• Hexafluorophosphoric acid
• 1H-Benzotriazole
• HBTU
• N-Benzyl-DL-serine Methyl Ester
• Dess-Martin periodinane
• 3-PHENYL-1H-PYRAZOLE-4-CARBALDEHYDE
• N-Bromosuccinimide
• AM2201
• Ethyl (R)-(-)-4-cyano-3-hydroxybutyate
• Nitrogen
• Azobenzene
• HOAt