Propanephosphonic acid anhydride

Propanephosphonic acid anhydride

Names
Preferred IUPAC name 2,4,6-Tripropyl-1,3,5,2λ5,4λ5,6λ5-trioxatriphosphinane-2,4,6-trione
Other names PPACA; PPAA; T3P; Propylphosphonic anhydride
Identifiers
CAS Number	68957-94-8
3D model (JSmol)	Interactive image
ChemSpider	100355
ECHA InfoCard	100.102.078
EC Number	422-210-5
PubChem CID	111923
UNII	I6EGD8839N
CompTox Dashboard (EPA)	DTXSID20219011
InChI InChI=1S/C9H21O6P3/c1-4-7-16(10)13-17(11,8-5-2)15-18(12,14-16)9-6-3/h4-9H2,1-3H3 Key: PAQZWJGSJMLPMG-UHFFFAOYSA-N
SMILES CCCP1(=O)OP(=O)(OP(=O)(O1)CCC)CCC
Properties
Chemical formula	C9H21O6P3
Molar mass	318.182 g·mol−1
Hazards
GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H290, H314
Precautionary statements	P234, P260, P264, P280, P301+P330+P331, P303+P361+P353, P304+P340, P305+P351+P338, P310, P321, P363, P390, P404, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Propanephosphonic acid anhydride (PPAA, T3P) is the trimeric anhydride of n-propylphosphonic acid. It is a useful reagent for peptide synthesis reactions, where it activates the carboxylic acid partner for subsequent reaction with a primary or secondary amine. ^[1] It is commercially available as 50% solution in DMF or ethyl acetate as a slightly yellow mixture. ^{[2] [3]}

Examples of T3P being used in the industrial syntheses of pharmaceuticals include the Pfizer synthesis of dacomitinib, the Neurosearch synthesis of SNDRIs such as PC44156003, ^[4] the last step of the synthesis of selinexor, ^[5] and the synthesis of darolutamide. ^[5]

References

1. Llanes García, A. (8 May 2007). "T3P: A Convenient and Useful Reagent in Organic Synthesis". Synlett. 2007 (08): 1328–1329. doi:10.1055/s-2007-980339.
2. Dunetz, Joshua R.; Magano, Javier; Weisenburger, Gerald A. (2016-02-19). "Large-Scale Applications of Amide Coupling Reagents for the Synthesis of Pharmaceuticals" . Organic Process Research & Development. 20 (2): 140–177. doi:10.1021/op500305s. ISSN   1083-6160 . Retrieved 2025-07-26.
3. "Propanephosphonic acid anhydride". Sigma-Aldrich.
4. Dan Peters, John Paul Redrobe, Elsebet Østergaard NIELSEN, WO2009090173 (2009 to Neurosearch A/S)
5. Flick, A. C., Leverett, C. A., Ding, H. X., McInturff, E., Fink, S. J., Mahapatra, S., Carney, D. W., Lindsey, E. A., DeForest, J. C., France, S. P., Berritt, S., Bigi-Botterill, S. V., Gibson, T. S., Liu, Y., O’Donnell, C. J. (8 April 2021). "Synthetic Approaches to the New Drugs Approved during 2019". Journal of Medicinal Chemistry. 64 (7): 3604–3657. doi:10.1021/acs.jmedchem.1c00208.