[4975-73-9]  · C17H31N3O  · N,N-Dicyclohexyl-4-morpholinecarboximidamide  · (MW 293.45)

(strong base; used as a catalyst for phosphorylation reactions in nucleoside chemistry)

Alternate Names: N,N-dicyclohexyl-4-morpholineformamidine; DMC.

Physical Data: mp 105.5 °C.

Solubility: sol pyridine.

Form Supplied in: white powder.

Preparative Methods: easily prepared by refluxing morpholine and 1,3-Dicyclohexylcarbodiimide.1

Phosphorylating Reagent.

DMC is a strong base that acts as a catalyst for phosphorylating reactions. It can be used to increase the solubility of salts of nucleoside 5-phosphoromorpholidates, and to catalyze their cyclization to cyclic 3,5-nucleoside phosphates in the presence of DCC (eq 1).2

Reaction of DMC salts of nucleoside 5-phosphoromorpholidates with phosphomonoesters gives nucleoside diphosphate derivatives.3 Similar reactions have been used for the synthesis of neosamine C-nucleoside diphosphates (eq 2).4

Preliminary formation of a morpholidate is not a necessary requirement and cyclization to 3,5-monophosphate derivatives is possible from DMC salts of the corresponding 5-monophosphate. Ring closure is obtained by action of DCC in dry pyridine (eq 3).5

Catalyst for Acylation Reactions in Nucleoside Chemistry.

DMC catalyzes acylation of nucleosides by carboxylic anhydrides. As an example, reaction with succinic anhydride gives a mixture of isomers but refined conditions have been described to yield N6-succinyl adenosine (eq 4).6

DMC allows simultaneous 2-hydroxybenzylation and phosphorylation when used together with methylthio-4H-1,2,3-benzodioxaphosphorin 2-oxide (MTBO) (eq 5).7

1. (a) Fieser, M.; Fieser, L. F. FF 1967, 1, 236. (b) Fieser, M.; Fieser, L. F. FF 1969, 2, 126.
2. Moffat, J. G.; Khorana, H. G. JACS 1961, 83, 649.
3. Roseman, S.; Distler, J. J.; Moffat, J. G.; Khorana, H. G. JACS 1961, 83, 659.
4. Tadano, K.; Tsuchiya, T.; Suami, T.; Rinehart, K. L., Jr. BCJ 1982, 55, 3840.
5. Bères, J.; Bentrude, W. G.; Balzarini, J.; De Clercq, E.; &OOuml;tvos, L. JMC 1986, 29, 494.
6. Sauer, C.; Schwabe U. ZN(B) 1981, 36, 750.
7. Eto, M.; Lio, M.; Omura, H.; Eto, M. ABC 1991, 55, 1999.

Jean-Claude Gesquière

Institut Pasteur, Lille, France.

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