Pyrimidines coupling with pyrrole

Tin Derivatives. 4-Stannylpyrimidines are highly active in couphng reactions at low temperature and will couple with an acid chloride to form ketones 166 in the absence of a catalyst (Scheme 70). 2-Stannylpyrimidines also react rapidly with acid chlorides to form ketones 167 in the absence of a catalyst.i Alkyl, aryl, and heteroaryl ketones in the benzenoid 5-position 168 are available from 5-stannylpyrimidines and carbonyl chlorides. The trimethylstannyl derivatives gave consistently shghtly higher yields than the tti( -butyl)staimyl pyrimidines. The reaction with pyrroles was run on A-alkylated or A-acylated... 

Utilized Pd(OAc)2 and SPhos 24 as the catalyst system to effectively catalyze Suzuki-Miyaura cross-couplings with only 1.1 equiv. of trifluoroborates [84e]. More recently, Molander and coworkers have developed a general cross-coupling system to many classes of heteroaromatic trifluoroborates employing Pd(OAc)2 and RuPhos 23 [84j]. Furan 135, thiophene 132, pyrrole 126, pyrazole 130, isoxazole 131, pyridine 127, pyrimidine 133, indole 129, benzothiophene 136, benzofuran 135, quinoline 128, and isoquinoUne could all be cross-coupled with only 1.04 equiv. of trifluoroborate salts, affording the corresponding cross-coupled products in good yield (Scheme 2.25). 

The Sonogashira reaction with TMSA could also be succes-fully accomplished in the coupling with different heteroaryles such as pyrroles, thiophenes, pyrimidines, purines, and quinazolines. ... 

The [AE, (addition-elimination)] and [AO, (addition-oxidation)] reactions of 5-bromopyrimidine with pyrroles and indoles for the synthesis of 4-(lR-pyr-rol-2-yl)-and 4-(lR-indol-3-yl)-5-(hetero)aryl-substituted pyrimidines by combination of the Suzuki-Miyaura cross-coupling and nucleophilic aromatic substitution of hydrogen reactions was carried out by Verbitskiy et al. (2012a). 

A similar reaction occurs with 2-pivaloylamino-4-oxopyrrolo[2,3-<7]pyrimidine. In this case the ratio of the 6-mercuri derivative to the 5-mercuri derivative was 10 1 <93H(36)1897>. Subsequent conversion of the mercuri compounds to the corresponding iodo derivatives provides the actual substrates for the palladium-catalyzed coupling reactions. Direct halogenation of the pyrrole ring has also been effected. In the only position available both chlorination (sulfuryl chloride) and bromination (NBS) have been achieved on the C-nucleoside (17 R = benzoylated ribose) (Equation (3)) <90JMC2750>. 

Isomerization of the coupling products of 1-arylpropargyl alcohols with electron-deficient halides generate a,j6-unsaturated aryl ketones, which undergo further condensation to afford heterocycles such as pyrroles and pyrimidines [25], For example, domino coupling-isomerization-condensation reactions of 1-phenylpropargyl alcohol (1", 2-bromothiazole, and methylhydrazine generated the enone 18, and the pyrazoline 19 was obtained by the reaction of methylhydrazine [25],... 

Indeed, a variety of heterocyclic compounds, such as thiophenes, dithiophenes, pyrroles, indoles, or carbazoles can be involved as carbon-centered nucleophiles in these reactions to modify the pyrimidine ring (Scheme 31) [120-122]. For instance, it has been shown that 5-bromopyrimidine reacts with dithiophene into the corresponding 5-substituted pyrimidine due to palladium-catalyzed aryl-aryl C-C cross-coupling reaction. On the other hand, 5-bromo-4-dithiophenyl-substituted pyrimidine was prepared from the same starting material through the SH (addition-oxidation) reaction catalyzed by a Lewis acid in the presence of potassium... 

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