Preparation of fused pyridine compounds

PURPOSE: To prepare the subject compounds which are intermediates for synthesizing an antitumor agent of a wide area spectrum by reacting an unsaturated compound with a halogenated aromatic compound in the presence of a Pd catalyst. CONSTITUTION: (A) A pyrido[2,3-d]pyrimidine represented by formula I (R 4 is H or an amino protecting group; Z 1 is H; Z 2 is H, methyl or ethyl, or together with Z 1 , forms a C-C bond) is reacted with (B) a benzoic acid derivative represented by formula II [R 1 is NHCH(COOR 2 )CH 2 CH 2 COOR 2 or OR 2 (R 2 is H or a carboxylic acid protecting group); X is Br or II in the presence of a Pd catalyst such as a Pd/trisubstituted phosphine complex to afford the objective compound represented by formula III. The reaction is carried out in the presence of a secondary or a tertiary amine, preferably in acrylonitrile under conditions of about 75-125°C (preferably ≤100°C). Diethyl N-{4-[2- pivaloylamino-4-hydroxypyrido[2,3-d]pyrimidin-6-ylethynyl]benzoyl}-L-glutamate is cited as an example of the compound. COPYRIGHT: (C)1996,JPO