6-Amino-2-trifluoromethyl-4//-pyrido

Heating 6-bromo- and 6-chloro-2-halomethyl- (99JHC1065) and 6-bromo-, 6-chloro- and 6-fluoro-2-phenyl-4/f-pyrido[l, 2-u]pyrimidin-4-ones (00JMC2814) in phenyl ether at 220 °C for 10 min yielded the appropriate 7-halo-1,8-naphthyridin-4-ols. 6-Amino-2-trifluoromethyl-4//-pyrido[l, 2-a]-pyrimidin-4-one was transformed into 7-amino-2-trifluoromethyl-l,4-dihy-dro-l,8-naphthyridin-4-one in 90% yield (98EJM383). 

Amino-2-trifluoromethyl-4//-pyrido[l,2-a pyrimidin-4-one (69) gave 7-amino-2-trifluoromethyl-1,8-naphthyridin-4(l//)-one (70) (PI12O, reflux 90%).533... 

Narsaiah and co-workers employed the Dimroth rearrangement in their preparation of novel 4-substituted-amino-5-trifluormethyl-2,7-disubstituted pyrido[2,3-< pyrimidines and evaluated their potential as antibiotics against Gram-positive and Gram-negative bacteria. Treatment of iminoether 121 with methyl amine in ethanol at room temperature for 3 h gave rise to 7V-methyl-2-methyl-7-phenyl-5-(trifluoromethyl)pyrido[2,3-i/)pyrimidin-4-amine 122 in 84% yield. This compound showed significant... 

Cyclization of 3-cyano-2-[(3-hydroxypropyl)amino]-5-(4-pyridyl)pyri-dine-l -oxide (298) in POCI3 yielded 9-cyano-7-(4-pyridyl)-3,4-dihydro-2/f-pyrido[],2-n]-pyrimidine I -oxide (299) (94EJM175). After heating 3-cyano-4-trifluoromethyl-6-phenyl-2-[(3-hydroxypropyl- and 3-hydroxybutyl)-amino] pyridines in boiling POCI3 for 1 h, the product was treated with aqueous NH4OH to yield 6-phenyl-8-trifluoromethyl-9-cyano-3,4-dihydro-2//-pyr-ido-[l,2-n]pyrimidine and its 4-methyl derivative (01CHE329). 

Similar ring systems were prepared <97JHC1693> by Coppo and Fawzi from the reaction of substituted ethyl 5-[methyl(methylsulfonyl)amino]-l 7/-pyrazole-4-carboxylates 119 with sodium hydride. This gave the 7-substitued 1,7-dihydro-l-methylpyrazolo[3,4-c][l, 2]thiazin-4(37/)-one 2,2-dioxides 120 in fair to good yield (Scheme 30). They also extended this synthesis by treating methyl 2-[methyl(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridinecarboxylate 121 with sodium hydride in dimethylformamide to yield l-methyl-7-(trifhioromethyl)-l//-pyrido[2,3-c][l,2]thiazin-4(3//)-one 2,2-dioxide 122 in 79% yield (Scheme 31) <98JHC499>. 

Reaction of 8-amino-2,5,6,7-tetrahydro-3//-pyrido[l,2,3-de]-l, 4-benzox-azin-3-one with tetrahydrophthalic anhydride gave 100 (91EUP406993). The hydroxy group of 9-[2,2,2-trifluoro-l-hydroxy-l-(trifluoromethyl)-ethyl]-2,3-dihydro-5//-pyrido-[l, 2,3-de]-l,4-benzoxazin-5-ones was acy-lated (79GEP2854727). Treatment of 9-fluoro-10-phenyl-3-methyl-7-oxo-2,3-dihydro-7//-pyrido-[l,2,3-de]-l,4-benzoxazine-6-carboxylate with CISO3H afforded the 10-(p-chlorosulphonylphenyl) derivative, which was converted to the 10-(p-aminosulphonylphenyl) derivative with NH3 (86EUP184384). 

---