9- Hydroxy-2-methyl-3- 2- ethyl 6,7,8,9-tetrahydro-477-pyrido

Treatment of 9-(ethoxymethoxy)-3- 2-[4-(6-fluoro-l,2-benzisoxazol-3-yl)-1,2,5,6-tetrahydro-1 -pyridyl] and -1 -piperidyl]ethyl -2-methyl-4/f-pyrido-[1,2-rz]pyrimidin-4-ones with cone. HCl afforded 9-hydroxy derivatives (95MIP4, OOMIPIO). 

Reaction of 2,3-dihydro-3-hydroxy-3-methyl- 240 (R = Me), or a mixture of 2,3-dihydro-3-hydroxy-3-aryl-57/-pyrido[l,2,3-dfe]-l,4-benzoxazin-5-ones 240 (R = Ar) and (8-aroylmethoxy)quinolin-2(l//)-ones 241 (R = Ar) with ethyl 2-(bromomethyl)acrylate in the presence of activated Zn and hydroquinone gave 8-[(2,3,4,5-tetrahydro-4-methylidene-5-oxo-2-furanyl)-methoxy]quinolin-2(l//)-ones (242) (97HCA1161). 6,7-Dihydro derivatives of 240 reacted similarly (00HCA349). 

Vilsmeier-Haack formylation of 2-(4-methyl-l-piperazinyl)-4//-pyrido-[l,2-n]pyrimidin-4-one with a mixture of POCI3 and DMF at 95°C gave a 3-formyl derivative (93FES1225) while ethyl 4-oxo-6,7,8, 9-tetrahydro-4//-pyrido[l,2-n]pyrimidine-2-acetate at 50 °C yielded a 9-dimethylaminomethylene-3-formyl derivative (01MI4). 3-Formyl-2-hydroxy-8-[2-(4-isopropyl-l,3-thiazol-2-yl)-l-ethenyl]-4//-pyrido[l,2-n]pyri-midin-4-one was obtained from the 3-unsubstituted derivative with oxalyl chloride-DMF reagent in CH2CI2 at room temperature for 3h (OlMIPl). 

Acylation of mesoionic pyrido[l,2-u]pyrimidin-4-ones 150 with aroyl chlorides in the presence of NEts yielded 2-aroyloxy-4//-pyrido[l,2-u]pyrimidin-4-ones 178 (96JHC663). None of the esters 178 could be rearranged to the 2-hydroxy-3-aroyl derivatives 179. The hydroxy group of 9-hydroxy-2-methyl-3- 2-[4-(6-fluoro-l,2-benzisoxazol-3-yl)-l-piperidinyl] ethyl -6,7,8,9-tetrahydro-4//-pyrido[l, 2-u]pyrimidin-4-one was acylated with hexadecanoic acid in CH2CI2 in the presence of dicyclohexylcarbodi-imide and 4-pyrrolidinopyridine at room temperature for 3 days in 80% yield (97MIP7). 

Dehydrogenation of ethyl 2-methyl-4-hydroxy-5,6,7,8-tetrahydro-4a//-pyrido]l,2-/j]pyridazine-3-carboxylate with mercury(II) acetate in ethanol at 45-50°C or over PtOa in boiling ethanol afforded anhydro 3-ethoxycar-bonyl-2-methyl-4-hydroxy-5,6,7,8-tetrahydropyrido[l,2-h]pyridazinium hydroxide (48) (71CPB159). The last compound could be reduced to the starting tetrahydropyrido[l,2-h]pyridazine over Pt02 in ethanol under hydrogen. 

The structures of ethyl 2-hydroxy-4-oxo-4//-pyrimido[2,l-a]isoquinoline-3-carboxylate (20) (89AJC2161), 6-[2-(4-methyl-l-piperazinyl)acetamido]-ll//-pyrido[2,l-b]quinazolin-ll-one (89JHC1229), and 6,7,8,9-tetrahydro-ll//-pyrido[2,l-b]quinazolin-ll-one (95KPS410) were determined by X-ray crystallography. 

Two polymorphic forms of 3- 2-[4-(6-fluorobenzisoxazol-3-yl)-l,2,3,6-tetrahydropyridin-1 -yl]ethyl -2-methyl-6,7,8,9-tetrahydro-4/7-pyrido[l, 2-a] pyrimidin-4-one (137 R = H) were prepared (99MIP1). Racemic 9-hydroxy-2-methyl-3- 2-[4-(6-fluorobenzo[i/]isoxazol-3-yl)-l,2,3,6-tetrahydro-l-pyridyl] ethyl -6,7,8,9-tetrahydro-477-pyrido[l,2-a]pyrimidin-4-one was resolved into its (R)- and (S)-isomers (00MIP10). 

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). 

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