O-(7-アザベンゾトリアゾール-1-イル)-N,N,N',N'-テトラメチルウロニウムヘキサフルオロホスファート

化学名:O-(7-アザベンゾトリアゾール-1-イル)-N,N,N',N'-テトラメチルウロニウムヘキサフルオロホスファート

CAS番号.148893-10-1

英語名:HATU

CBNumberCB0122630

MFC10H15F6N6OP

MW380.24

MOL File148893-10-1.mol

别名

O-(7-アザベンゾトリアゾール-1-イル)-N,N,N',N'-テトラメチルウロニウムヘキサフルオロホスファート

HATU

O‐(7‐アザベンゾトリアゾール‐1‐イル)‐N,N,N′,N′‐テトラメチルウロニウムヘキサフルオロりん酸塩

O-(7-アザベンゾトリアゾール-1-イル)-N,N,N',N'-テトラメチルウロニウムヘキサフルオロホスファート物理性質

融点	183-188 °C (dec.)
RTECS 番号	XZ5633000
貯蔵温度	2-8°C
溶解性	>16mg/mL in DMSO
外見	powder to crystaline
色	White to Almost white
水溶解度	アセトニトリルに可溶。水に不溶。
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 データベース	148893-10-1(CAS DataBase Reference)
EPAの化学物質情報	1H-1,2,3-Triazolo[4,5-b]pyridinium, 1-[bis(dimethylamino)methylene]-, hexafluorophosphate(1-), 3-oxide (148893-10-1)

安全性情報

主な危険性	Xi,Xn,E
Rフレーズ	36/37/38-20/21/22-2
Sフレーズ	26-37/39-36/37-36-35
RIDADR	1325
WGK Germany	3
F	10-21
国連危険物分類	4.1
容器等級	Ⅱ
HSコード	29339999

危険有害性情報のコード(GHS)

O-(7-アザベンゾトリアゾール-1-イル)-N,N,N',N'-テトラメチルウロニウムヘキサフルオロホスファート価格

製品番号	包装	価格	製品説明	購入
富士フイルム和光純薬株式会社(wako) W01W0101-2612	25g	￥25300	O-(7-アザベンゾトリアゾール-1-イル)-N,N,N',N'-テトラメチルウロニウムヘキサフルオロりん酸塩【HATU】 98.0+% (HPLC)	購入
富士フイルム和光純薬株式会社(wako) W01W0101-2612	100g	￥72600	O-(7-アザベンゾトリアゾール-1-イル)-N,N,N',N'-テトラメチルウロニウムヘキサフルオロりん酸塩【HATU】 98.0+% (HPLC)	購入
富士フイルム和光純薬株式会社(wako) W01W0101-2173	25g	￥42400	O-(7-アザベンゾトリアゾール-1-イル)-N,N,N',N',-テトラメチルウロニウムヘキサフルオロりん酸塩	購入
富士フイルム和光純薬株式会社(wako) W01MAS067222	25g	￥15600	ヘキサフルオロりん酸O-(7-アザベンゾトリアゾール-1-イル)-N,N,N',N'-テトラメチルウロニウム	購入
富士フイルム和光純薬株式会社(wako) W01H011043	1g	￥4000		購入

O-(7-アザベンゾトリアゾール-1-イル)-N,N,N',N'-テトラメチルウロニウムヘキサフルオロホスファート化学特性,用途語,生産方法

外観
白色～わずかにうすい黄色, 結晶～粉末又は塊
溶解性
アセトンに溶け、水及びエタノールに難溶である。
用途
本製品は、試験研究用途に限定して販売を行っております。
使用上の注意
不活性ガス封入
説明
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.
化学的特性
White crystalline to off-white powder
使用
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.
反応性
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%.
合成
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%).
参考文献
[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.