2- Methylsulfonyl-pyrimidines

To study the ort/m-directing influence of the fluorine atoms, 2,4-difluoropyrimidine (3) and 4-fluoro-2-(methylsulfonyl)pyrimidine (4) have been prepared from the precursor chlorides 1 and 2 by treating with potassium fluoride in tetraglyme in the presence of 18-crown-6. 19... 

The process starts from a Knovengol condensation of ethyl isobutyryl acetate with 4-fluorobenzaldehyde. The reaction of S -methyl isothiourea sulfate with a,P-unsaturated ketone followed by oxidation with DDQ gives 2-(methylthio)pyrimidine. This intermediate was further oxidized by w-CPBA to yield 2-(methylsulfonyl)pyrimidine. Aromatic substitution with methyl amine and sulfonylation afford methanesulfonamide derivative. The required alcohol can be synthesized by DIBAL reduction of the corresponding ester as... 

The 9-methylsulfonyl-pyrimido[l,6-tf]pyrimidin-6,8-dione 210 was obtained during attempted mesylation of the 6-[(3-hydroxypropyl)amino]uracil 209 (Equation 25). The methanesulfonyl group of 209 was removed by reduction with Raney Ni to yield 68 <1999JHC453>. 

CH3 KNOj h2so4 to 1 2- Methylsulfonyl-5-(4-nitro-phen-yl) -pyrimidin 82 223-225 (Ethanol) 3... 

It is assumed that the heterocyclic core structure is responsible for the appropriate orientation of the aromatic rings in space and finally for binding to the enzyme. A wide variety of heterocycles can serve as templates, i.e. pyrrole, thiazole, oxazole furane, furanone, imidazole, isoxazole, pyrimidine and thiophene, but at the moment pyrazole and cylopentenone seem to be the most appropriate for achieving COX-2 specificity. For optimal activity, one aromatic ring must be substituted with a methylsulfonyl or a sulfonamide substituent in the para position. Substitution at position 4 of one of the aromatic systems with a sulfonamide or a methylsulfonyl group is essential for COX inhibition. Replacement of the methylsulfonyl group by a sulfonamide group reduces COX-2 selectivity but improves oral bioavailability. 

Pyrimidinones, 5-methylsulfonyl-synthesis, 3, 138 Pyrimidin-2-ones IR spectra, 3, 64 Pyrimidin-2( 1H)-ones acidic pKa, 3, 60 alkylation, 3, 90 nitration, 3, 69 pKa> 3, 60 reduction, 3, 75 synthesis, 3, 132 Pyrimidin-4(3/7)-ones alkylation, 3, 90 synthesis, 3, 132 thiation, 3, 89 Pyrimidinophanes synthesis, 7, 768, 774 Pyrimidinopurinophanes synthesis, 7, 766 Pyrimidin-2-yl thiocyanate synthesis, 3, 95... 

Methylsulfonyl)-3-phenyl-3//-l,2,3-triazol[4,5-d]pyrimidine 176 was prepared by the reaction of 175 with sodium methyl sulfide, followed by oxidation with potassium permanganate in acetic acid. A nucleophilic substitution reaction on 176 with potassium cyanide gave 182, but the same reaction did not take place on 175. Treatment of 176 with sodium methoxide... 

A halogen substituent at C-4 of the pyrazolo[3,4-c ]pyrimidine ring system is readily replaced by active methylene reagents (76S824, 76YZ1352). For example, treatment of the derivatives (207) with active methylene reagents in the presence of sodium hydride results in the formation of derivatives (208) in 70-80% yield (Equation (21)). The methylsulfonyl derivative (209) is converted into the carboxamide (211) when treated with cyanide ion intermediacy of the nitrile (210) seems most likely (Scheme 16) <82JMC1334>. 

Pyrimidin 2-Methylsulfonyl-5-(4-nitro-phenyl)- E16d, 303 (Nitrie-rung)... 

Pyridin 4-Diethylamino-5-methyl-3-methylsulfonyl- E7b/2, 461 [5-(S02 —R)-pyrimidin + H3C-C = C-NR2] Schwefelsaure -(benzyl-ethyl-amid)-dimethylamid Ell, 1023 (N-Benzylier.)... 

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