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

^ 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.
^ 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.
^ "Propanephosphonic acid anhydride". Sigma-Aldrich.
^ Dan Peters, John Paul Redrobe, Elsebet Østergaard NIELSEN, WO2009090173 (2009 to Neurosearch A/S)
^ ^a ^b 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.

[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.

[b598-2] 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)

[Flick-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.

[1]

[2]

[3]

[4]

[5]