Synthesis of N,N-dimethylpropanediamide and its utility for the preparation of 2-(acetamidomethyl)-4-aryloxazoles

Synlett

Volumn , Issue 8, 2004, Pages 1334-1338

  Ragan, John A ^a   Burmaster, Michael ^a   Hill, Paul D ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

Annulation; Bromo ketone; Heterocycle; N,N dimethylpropanediamide; Oxazole

Indexed keywords

DIAMIDINE DERIVATIVE; N,N DIMETHYLPROPANEDIAMIDE; OXAZOLE DERIVATIVE; PROPIONAMIDE DERIVATIVE; UNCLASSIFIED DRUG;

AMINATION; ARTICLE; CHEMICAL REACTION; CHEMICAL STRUCTURE; MOLECULAR DYNAMICS; PROTON NUCLEAR MAGNETIC RESONANCE; SUBSTITUTION REACTION; SYNTHESIS;

EID: 3142736529     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2004-825607     Document Type: Article

References (9)

1. Hartner, F. W. In Comprehensive Heterocyclic Chemistry II, Vol. 3; Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V., Eds.; Pergamon: Oxford, 1996, 262-318; and references therein.
2. (a) Friedman, B. S.; Sparks, M.; Adams, R. J. Am. Chem. Soc. 1937, 59, 2262.
3. (b) Panek, J. S.; Beresis, R. T. J. Org. Chem. 1996, 61, 6496.
4. (c) Takechi, H.; Oda, Y.; Hishizono, N.; Oda, K.; Machida, M. Chem. Pharm. Bull. 2000, 48, 1702.
5. (a) Gellman, S. H.; Dado, G. P.; Liang, G.-B.; Adams, B. R. J. Am. Chem. Soc. 1991, 113, 1164.
6. (b) Interestingly, both Beilstein and Sci-Finder searches for bis-amide 1 gave the preceding reference for its synthesis. We suspect that this was a typographical error upon entry in these databases, as there is no description of compound 1 in the Gellman paper. The Beilstein reference gives a reaction time of 63 h and 81% yield, values which are identical to the first experimental procedure in the paper, in which the mono-N,N-dimethylamide of malonic acid (3) is prepared en route to N,N,N′-trimethylpropanediamide.
7. This effect has recently been noted in the esterification of carboxylic acids activated at the α-carbon with phosphonates, esters, sulfones, and nitriles. A mechanism proceeding through an acyl ketene was supported by trapping of the ketene with DCC in a [4+2] cycloaddition: Shelkov, R.; Nahmanh, M.; Melman, A. J. Org. Chem. 2002, 67, 8975.
8. 1H NMR or GC/MS.
9. Actually, the opposite enantiomer of the other diastereomer would be formed. For example, in the condensation of the R-acid chloride with racemic amine, the products are amide 10 and (ent)-11. This has no impact on the achiral HPLC and NMR analyses, however.