title: Synthesis of quinazolin-4(3H)-ones via amidine N-arylation.
abstract: Pyrido[4,3-d]pyrimidin-4(3H)-one (1) was prepared by reacting 2-trifluoromethyl-4-iodo-nicotinic acid (2) with amidine 9a catalyzed by Pd(2)(dba)(3) and Xantphos, followed by cyclization effected with HBTU and subsequent demethylation using PhBCl(2). The amidine arylation method was found applicable for the syntheses of quinazolin-4(3H)-ones. Thus, reaction of 2-bromo or 2-iodo benzoate esters with amdidines afforded substituted quinazolin-4(3H)-ones in 44-89% yields.
authors.affiliation: Chemical R & D - Pharmaceutical Science Worldwide Research and Development, Groton Laboratories, Pfizer Inc., Groton, Connecticut 06340, USA. bryan.li@pfizer.com
authors.forename: Bryan
authors.initials: B
authors.lastname: Li
authors.forename: Lacey
authors.initials: L
authors.lastname: Samp
authors.forename: John
authors.initials: J
authors.lastname: Sagal
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Hayward
authors.forename: Christine
authors.initials: C
authors.lastname: Yang
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000578:Amidines / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D006846:Hydrocarbons, Halogenated / Q000737:chemistry*; D015394:Molecular Structure; D009539:Nicotinic Acids / Q000737:chemistry*; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry; D052999:Quinazolinones / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C582694:2-trifluoromethyl-4-iodo-nicotinic acid; D000578:Amidines; D006846:Hydrocarbons, Halogenated; D009539:Nicotinic Acids; D011744:Pyrimidinones; D052999:Quinazolinones; C582693:pyrido(4,3-d)pyrimidin-4(3H)-one