4-Pyrimidinone bromination

Aldehydes, arylideneanilines, carboxylic acids and orthoesters have been used as one-oarbon units for binding the two amino functions of 4-amino-l-alkyl-3-propylpyrazole-5-oarboxamide to give l,6-dihydro-pyrazolo[4,3-<7]pyrimidin-7-ones <05MC619 05JHC751>. A modified efficient synthesis of variably substituted pyrazolo[4,3-<7]pyrimidm-7-ones has been described using a pyrazole-5-carboxylic acid, which was selectively brominated at position 4 and then converted into the carboxamide. Microwave irradiation gave better yields in the conversion of the carboxamides to pyrazolo[4,3-J]pyrimidinones <05JHC1085>. 

IV. The reaction of nucleofilic substitution bromine in methyl (benzyl)bromid by 0-anion generated from 2-methyl(benzyl)thio-4- pyrimidinon. 

The second stage is a reaction S-sodium compound of 2-thiouracil with methyl(benzyl)bromid and obtaining of 2-thiomethyl(benzyl)-4-pyrimidinon. Reaction of nucleophilic substitutiof bromine in methyl (benzyl) bromid by anion, generated from 2-thiouracil is shown on scheme... 

IV Stage. The Reaction of Nucleophilic Substitution Atom of the Bromine in Methyl (benzyl) bromid by O-anion 2-methyl(benzyl)thio-4-pyrimidinon... 

Another Sml2-mediated domino process was reported by the Baran group in the synthesis of (+)-Cortistatin A 51 [22]. When the bromoketone 47 was treated with Sml2 in the presence of the additive DMPU (l,3-dimethyl-3,4,5,6-tetrahydro-2(lH)-pyrimidinone), a cyclopropane fragmentation occurred to form an a-bromo radical 48, which underwent subsequent reduction by Smij and then bromide elimination to give 49 with a newly formed C=C double bond and a Sm(lll) enolate. After a few minutes, the addition of 2,4,4,6-tetrabromo-2,5-cyclohexadienone (TBCHD) resulted in the a-brominated product 50, which was converted into cortistatin A 51 (Scheme 5.13). 

Further annelation to pyrimidine ring based on substitution of fluorine at 5-position was used in patent literature. Alantos Pharmaceuticals in a course of matrix metaUoprotease inhibitors development described an efficient pyrazole annelation to pyrimidine. The synthesis of key intermediate - pyrimidine dicarbox-ylic acid 188 was accomplished in 3 step bromination - carbonylation - oxidation sequence from pyrimidinone 185. The acid was converted to the corresponding... 

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