4- Methyl-2-pyridyl-pyrimidine

Methyl-2-(2-pyridyl)pyrimidine, M-00304 (4-Methyl-2-pyridyl)-l,2,4-triazino[5,6-y)[4,7]-phenanthroline, M-00305... 

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). 

Heating 4-oxo-4//-pyrido[l, 2-n]pyrimidine-3-diazonium tetrafluorobo-rate and its 8-methyl derivative in alcohol at 60-90 °C for 15 min to 5h gave alkyl 1-(2-pyridyl)- and 1-(4-methyl-2-pyridyl)-l//-1,2,3-triazole-4-carboxylates (00H(53)1793). 

Two polymorphic forms of 3- 2-[4-(6-fluorobenzisoxazol-3-yl)-l,2,3,6-tetrahydropyridin-l-yl]ethyl -2-methyl-6,7,8,9-tetrahydro-4//-pyrido[l,2-n] pyrimidin-4-one (137 R = H) were prepared (99MIP1). Racemic 9-hydroxy-2-methyl-3- 2-[4-(6-fluorobenzo[r/ isoxazol-3-yl)-l,2,3,6-tetrahydro-l-pyridyl] ethyl -6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidin-4-one was resolved into its (R)- and (5)-isomers (OOMIPIO). 

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). 

Cyclization of methyl 2-[2-benzoyl-2-ethoxycarbonyl-l-vinyl)amino]-3-[(4-methyl-2-pyridyl)amino]acrylate (311) afforded the 3-amino-8-methyl-4//-pyrido[l,2-n]pyrimidin-4-one derivative 312 (97JHC1511). 

Dodecyloxy-3-(2-chloroethyl)-2-methyl-4//-pyrido[l,2-n]pyrimidin-4-one 317 was obtained by cyclization of 3- l-[(3-dodecyloxy-2-pyridyl)ami-no]ethylidene -4,5-dihydro-2(3//)-furanone (316) in boiling POCI3 (95MIP4). 

Cyclization of ethyl A -(2-pyridyl)-2-methyl)- and A -(5-ehloro-2-pyridyl)-malonamates in a mixture of POCI3 and PPA at 130°C gave 2-ehloro-3-methyl- and 2,7-diehloro-4/7-pyrido[l,2-n]pyrimidin-4-ones in 26 and 61% yields, respeetively (00BMC751). 

Shur and Israelstam carried out the cyclization of 2-pyridylaminomethy-lenemalonates (1001) in polyphosphoric acid at 110°C for 4 hr (68JOC3015). They reported that pyrido[ 1,2-a]pyrimidine-3-carboxylates (1002) were obtained, even if they started from A/-(6-methyl- or 4,6-dimethyl-2-pyri-dyl)aminomethylenemalonates (1001, R = Me, R1 = H, 4-Me). However, it was later demonstrated that, in the case of the 6-methyl derivative (1001, R = Me, R1 = H), instead of the pyrido[ 1,2-a]pyrimidine-3-carboxylate (1002, R = Me, R1 = H), the ethyl, hydrogen Al-(6-methyl-2-pyridyl)ami-nomethylenemalonate (378, R = Me) was probably obtained. The latter... 

Pyrido[l,2-a]pyrimidine-3-carboxylate (1010, R = Me) was prepared in 90% yield on the cyclization of diethyl A-(3-cyano-4-methyl-2-pyridyl)ami-nomethylenemalonates by heating in Dowtherm A at 255°C for 1.5 hr (84KGS799). 

The ring closure of diethyl /V-(6-methyl-2-pyridyl)aminomethylenemalo-nate(1001, R = Me,R = H) was carried out on a large scale in chlorobenzene on the action of a mixture of phosphoryl chloride and polyphosphoric acid at 125-130°C for 10-12 hr to give the hydrochloride of pyrido[l,2-a]pyrimidine-3-carboxylate (1002, R = Me, R1 = H) in good yield after treatment of the reaction mixture with ethanol (77MIP1). 

Sodium borohydride, even in a very large excess, reduced methyl 2-none-noate and methyl cinnamate incompletely to mixtures of saturated esters, unsaturated alcohols and saturated alcohols [1061]. On the other hand, a,p-unsaturated esters of pyridine and pyrimidine series were converted predominantly and even exclusively to saturated alcohols. Methyl 3-(7-pyri-dyl)acrylate gave, on refluxing for 1-2 hours in methanol with 10 mol of sodium hydride per mol of the ester, 67% of 3-(y-pyridyl)propanol and 6% of 3-(y-pyridyl)-2-propenol methyl 3-(6-pyrimidyl)acrylate gave 77% of pure 3-(6-pyrimidyl)propanol [1061]. 

Ozone oxidation of 6-aryl-2-methylthiopyrido[2,3-methyl sulfone with /ra j-4-aminocyclohexanol afforded the amino pyridopyrimidinone derivative 176 <2002W02002018380>. Amination of 6-dimethoxyphenyl-8-ethyl-2-methylthiopyrido[2,3-t7 pyrimidin-7-one with 4-aminopyridine and LiNH2 in THF at 50°C produced the 2-[(4-pyridyl)amino] derivative 177 <2003W02003027110>. 

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