148893-10-1

Basic information

• Product Name: HATU
• Synonyms: 2-(7-Azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate;HATU >=98.0% (CHN);1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate, ChemDoseTM tablets;O-(7-AZABENZOTRIAZOL-1-YL)URONIUM HEXAFLUORO-PHOSPHATE;O-(7-AZABENZOTRIAZOLE-1-YL)-N, N,N',N'-TETRAMETHYLURONIUM HEXAFLUOROPHOSPHATE;O-(7-AZABENZOTRIAZOL-1-YL)-1,1,3,3-TETRAMETHYLURONIUM HEXAFLUOROPHOSPHATE;O-(7-AZABENZOTRIAZOL-1-YL)-N,N,N',N'-TETRAMETHYLURONIUM HEXAFLUOROPHOSPHATE;N,N,N',N'-TETRAMETHYL-O-(7-AZABENZOTRIAZOL-1-YL)URONIUM HEXAFLUOROPHOSPATE
• CAS NO: 148893-10-1
• Molecular Formula: C₁₀H₁₅N₆O*F₆P
• Molecular Weight: 380.23
• EINECS: 1308068-626-2
• Product Categories: Peptide coupling agents;Pharmaceutical Intermediates;Amino Acid Derivatives;Coupling Reagent;PROTECTED AMINO ACID & PEPTIDES;Peptide Coupling Reagents;Peptide;Miscellaneous Reagents;peptides;carboxylic ester;HATU
• Mol File: 148893-10-1.mol
• Article Data: 2

Chemical Properties

• Melting Point: 183-188 °C (dec.)
• Boiling Point: 176 °C at 760mmHg
• Appearance: White crystalline to off-white powder
• Storage Temp.: 2-8°C
• Water Solubility: Soluble in acetonitrile. Insoluble in water.
• CAS DataBase Reference: HATU(CAS DataBase Reference)
• NIST Chemistry Reference: HATU(148893-10-1)
• EPA Substance Registry System: HATU(148893-10-1)

Safety Data

• Hazard Codes: Xi,Xn,E
• Statements: 36/37/38-20/21/22-2
• Safety Statements: 26-37/39-36/37-36-35
• RIDADR: 1325
• WGK Germany: 3
• RTECS: XZ5633000
• F: 10-21
• HazardClass: 4.1
• PackingGroup: Ⅱ
• Hazardous Substances Data: 148893-10-1(Hazardous Substances Data)

Usage

Chemical Properties

White crystalline to off-white powder

Uses

Different sources of media describe the Uses of 148893-10-1 differently. You can refer to the following data:
1. HATU is a peptide coupling reagent.
2. HATU 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.
3. Reagent for: Synthesis of Aurora A kinase inhibitors HPLC assay to determine D- and L- acid enantiomers in human plasma Amide bond formation reactionsCatalyst for: Selective acylation Selecocyclization-oxidation deselenation sequence

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%).

Synthetic route

pyridine-4-carboxylic acid (55-22-1) + C108H81Fe2N15(4+)*4C2F6NO4S2(1-) + N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate (148893-10-1) → C126H90Fe2N18O3(4+)*4F6P(1-)

Conditions	Yield
Stage #1: pyridine-4-carboxylic acid; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 3.25h; Sealed tube; Inert atmosphere; Stage #2: C108H81Fe2N15(4+)*4C2F6NO4S2(1-) In acetonitrile at 20℃; for 72h;	96%

4-nitrobenzyl chloride (619-73-8) + N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate (148893-10-1) → 3-((4-nitrobenzyl)oxy)-3H-[1,2,3]triazole[4,5-b]pyridine (353262-26-7)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane Reflux;	95%

C16H20O6 + N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate (148893-10-1) → C21H22N4O6

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0℃; for 0.5h; Darkness; Inert atmosphere;	95%

4-chloro-2-cyclopropyl-1-[(4-fluorophenyl)sulfonyl]-1,2,2’,3’,5’,6’-hexahydrospiro[indole-3,4’-thiopyran]-5-carboxylic acid 1‘,1‘-dioxide + N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate (148893-10-1) → 4-chloro-2-cyclopropyl-1-[(4-fluorophenyl)sulfonyl]-5-[(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yloxy)carbonyl]-1,2,2’,3’,5’,6’-hexahydrospiro[indole-3,4’-thiopyran]-1‘,1‘-dioxide

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20℃;	91%

N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate (148893-10-1) + pyrrole-2-carboxyl acid (634-97-9) → 3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl 1H-pyrrole-2-carboxylate

Conditions	Yield
With triethylamine In acetonitrile at -30℃; for 1.5h; Inert atmosphere; Schlenk technique;	90%

carboxy MIDA boronate + N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate (148893-10-1) → C10H10BN5O5

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In [D3]acetonitrile at 20℃;	90%

Downstream Products

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