Synthesis 2015; 47(03): 377-386
DOI: 10.1055/s-0034-1378675
paper
© Georg Thieme Verlag Stuttgart · New York

Efficient Synthesis of 1,3-Disubstituted 1,3-Dihydro-2H-imidazo[5,1-b]quinazolin-9-ones by an Intramolecular Mannich-Type Reaction

Julien Leclercq
,
Moshine Driowya
,
Nathalie Flouquet
,
Pascal Berthelot
,
Nicolas Lebegue*
Further Information

Publication History

Received: 22 July 2014

Accepted after revision: 19 September 2014

Publication Date:
13 November 2014 (eFirst)

Abstract

A general and efficient method has been developed for the synthesis of 1,3-disubstituted 1,3-dihydroimidazo[5,1-b]quinazolin-9-ones. The process involves an intramolecular Mannich­-type reaction of a 2-aminomethylquinazolin-4-one derivative with an aldehyde, and gives diastereomeric mixtures of the minor cis- and major trans-cycloadducts.

Supporting Information

 
  • References

    • 1a Johne S. Prog. Chem. Org. Nat. Prod. 1984; 46: 159
    • 1b Johne S In The Alkaloids: Chemistry and Pharmacology . Vol. 29. Brossi A. Academic Press; New York: 1986. Chap. 2, 99
    • 1c Besson T, Chosson E. Comb. Chem. High Throughput Screening 2007; 10: 903
  • 2 Horton DA, Bourne GT, Smythe ML. Chem. Rev. 2003; 103: 893
  • 3 Examples include raltitrexed (marketed as Tomudex for treatment of colorectal cancer), ispinesib (Phase II for solid tumors), and tempostatin (Phase II for bladder cancer).
  • 4 Jankowski F, Verones V, Flouquet N, Carato P, Berthelot P, Lebegue N. Tetrahedron 2010; 66: 128
  • 5 Jen T, Dienel B, Bowman H, Petta J, Helt A, Love B. J. Med. Chem. 1972; 15: 727
  • 6 Hardtmann GE, Koletar G, Pfister OR. J. Med. Chem. 1975; 18: 447
  • 7 Venuti MC, Jones GH, Alvarez R, Bruno JJ. J. Med. Chem. 1987; 30: 303
  • 8 Chern J.-W, Tao P.-L, Wang K.-C, Gutcait A, Liu S.-W, Yen M.-H, Chien S.-L, Rong J.-K. J. Med. Chem. 1998; 41: 3128
  • 9 Hirth KP, Mann E, Shawyer LK, Ullrich A, Keri G, Szekely I, Bajor T, Haimichael J, Orfi L, Levitzki A, Gazit A, Tang PT, Lammers R. US 6331555, 2001
  • 10 Varma RS, Bahadur S, Agnihotri AK. J. Chem. Eng. Data 1981; 26: 103
  • 11 Udupi RH, Kushnoor A, Bhat AR. J. Indian Chem. Soc. 1999; 76: 461
  • 12 Arend M, Westermann B, Risch N. Angew. Chem. Int. Ed. 1998; 37: 1044
  • 13 Knight SD, Overman LE, Pairaudeau G. J. Am. Chem. Soc. 1995; 117: 5776
  • 14 See the experimental section and the Supporting Information for details.