Process for preparing phosphorodiamidites

Organic compounds -- part of the class 532-570 series – Organic compounds – Phosphorus esters

Reexamination Certificate

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Reexamination Certificate

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10540160

ABSTRACT:
A method of phosphorodiamidite production comprising the steps of reacting a phosphorus trihalide with a dialkyl amine in a polar solvent to form an intermediate compound. This intermediate compound is then subsequently reacted with an hydroxylalkyl compound and a dialkyl amine in the presence of a non-polar cosolvent. Following filtration to remove the solid by-product the two solvents form separate layers. This is advantageous as the upper, non-polar solvent, layer contains the high-purity phosphorodiamidite product.

REFERENCES:
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patent: 2003/0236233 (2003-12-01), Shamblee et al.
patent: 62212395 (1987-09-01), None
patent: WO 03/087130 (2003-10-01), None
patent: WO 03/106468 (2003-12-01), None
Nielsen et al., Improved synthesis of 2-cyanoethyl N, N, N′, N′-tetraisopropylphosphorodiamidite, (Nucleic acids Research (1987), 15 (8), 3626).
Patent Abstracts of Japan, vol. 012 No. 075 (C-480), Mar. 9, 1988, of JP 62 212395 A, (Nippon Zeon Co. Ltd), Sep. 18, 1987.
Hamamoto S. Takaku H: “New approach to the Synthesis of Deoxyribonucleoside Phosphoramidite Derivatives”,Chemistry Letters, Chemical Society of Japan, Tokyo, JP, vol. 8, 1986, pp. 1401-1404, XP002902766.
Pfleiderer W. et al: “Inhibition of HIV-a replication and activation of RNase L by phosphorothioate/phosphodiester 2′,5′-oligoadenylate derivatives”,,Journal of Biological Chemistry, American Society of Biological Chemists, Baltimore, Md., US, vol. 270-, No. 11, Mar. 17, 1995, pp. 5963-5978, XP002079044.
Houalla D, et al.: “Preparations ET Quelques Proprietes DE Composes Contenant LA Liaison Phosphore Trivalent-Azote”,Bulletin de La Societe Chimique de France, Societe Francaise de Chimie, Paris, France, 1965, pp. 2368-2373, pp. 2368, 2370.
Fluka Chemika, Biochemika und Analytika Katalog 1997, Fluka Chmie AG XP002277275, p. 434.

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