Pyridine pyrimidones

Chlorination of 2-hydroxy-4//-pyrido[l,2-n]pyrimidin-4-one with NCS in a mixture of AcOH and TFA at room temperature for 72 h yielded a 3-chloro-2-hydroxy derivative (95JMC4687). Bromination of 2-chloro-4//-pyrido[l, 2-n]pyrimidone with Br2 in a mixture of CH2CI2 and pyridine at room temperature for 15 min gave a 3-bromo derivative (00BMC751). 

Extension of this work by studying the reaction of 3-methyl-5-nitro-pyrimidin-4(3//)-one with -X-arylketones in the presence of ammonium acetate surprisingly revealed the formation of a mixture of 4-arylpyrimidines and 6-arylpyridin-2(l//)-ones (00JCS(P1)27). The ratio between pyridine and pyrimidine formation is dependent on the substituent X. With electron-donating substituents the formation of the pyridin-2(l//)-ones is favored, with electron-attracting substituents the formation of the pyrimidine derivatives (Scheme 21) In the formation of the 6-arylpyridin-2(l//)-ones the C-4- C-5-C-6 part of the pyrimidone-4 is the building block in the construction of the pyridine ring. Therefore, the pyrimidone can be considered as an activated o -nitroformylacetic acid (Scheme 21). 

An alternate scheme for preparing these compounds starts with a prefabricated pyrimidone ring. Aldol condensation of that compound (95), which contains an eneamide function, with pyridine-3-aldehyde (80), gives the product 96. Catalytic hydrogenation gives the product of 1,4 reduction. The resulting pyrimidinedione, of course exists in the usual tautomeric keto (97a) and enol (97b) forms. Reaction with phosphorus oxyxchloride leads to the chloro derivative 98. Displacement with methoxide gives 99. Reaction of this last intermediate with the furylalkylamine derivative 92 leads to the H-2 blocker lupitidine (100) [22]. 

Pyrimidines are pyridines with two nitrogen atoms having a 1,3-relationship 66. They occur in nucleic acids as pyrimidine bases such as cytosine 67 and thymine 68 and you will notice that these are pyrimidones. An important new type of anti-cancer drug Glivec 69 has a pyrimidine core with a linked pyridine ring. 

As mentioned earlier, electrophilic substitution on unactivated pyrimidines is of little importance. But, as with pyridine, the pyrimidine nucleus can be activated towards electrophilic attack by employing N-oxides or pyrimidones, for the same reasons as were discussed in Chapter 5. 

In the IR spectra of six-membered heterocycles containing one or more carbonyl groups in the ring (pyridin-2- and -4-ones, the pyrones, and pyrimidones) one of the higher frequency bands in the 1700-1500 cm-1 region can usually be... 

Certain ylides react with arylcyclopropenones via 1,4-addition to give a-pyrone and its heterocyclic derivatives the formation of the l,3-oxazin-6-one 336 from reaction of the pyridine-iV-imine 335 with 14 is representative. Pyrimidones, pyridines and related... 

Cyclization of the Michael adducts formed from enehydrazines and DMAD, for example (136), in the presence of ppa proceeds to give pyrimidone-fused 1,2-diazepines (137) through formal closure of the d bond (Equation (22)) <92JCS(P1)1287>. In contrast, thermolysis of the adducts (136) in tetralin preferentially provides fused pyridine and pyrrole ring products. 

Thieno[2,3- /]pyrimidines have been synthesized from 5-acylamino-2,3-dialkylthiophen-4-aldehydes. 2-Amino-3-cyano-thiophens have been transformed into the 2-cyanamino-3-cyano-thiophens and ring-closed to 4-aminothieno[2,3-Raney nickel to the 4-oxo-pyrimidine (263). ... 

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