2- fluoro-4-phenyl pyrimidine

Besides chlorine, another living group can be involved into nucleophilic fluori-nation. Preliminary transformation of chloropyrimidines 41 to trimethylammonium salts 42 facilitate further ftuorination. In this case the reaction proceeds in very mild conditions - under 5 °C (Scheme 11) [72, 73], This approach allows to fluorinate pyrimidines deactivated by electron-donated groups. When heated with potassium fluoride in ethylene glycol 2,6-dimethoxy-4-trimethylammoniopyrimidine salts were converted into the 4-fluoroderivatives in 42 % yield [74] Analogously fluorination can be accomplished in 2-d position, which was illustrated by preparation of 2-fluoro-4-phenyl-pyrimidine [75],... 

Comparison of this reactivity order with that found in the amination of 2-X-4-phenyl pyrimidines (SCH3 Br = Cl > F > SO2CH3 I > (013)3 > CN see Table 11.5 in Section ll,C,l,d) shows that these reactivity orders differ considerably. The fluoro substituent, especially, which has in the pyrimidine series about the same reactivity order as the chloro or bromo atom, shows in the 1,2,4-triazine series a low ANRORC activity. Comparison of both series of reactivities is, however, a delicate matter, mainly because the yields obtained for the amino compounds in the 1,2,4-triazine series are much lower than those obtained in the pyrimidine series, because of the occurrence of many side reactions, such as ring contraction, dehalogenation, ring transformations, and degenerate ring transformations... 

During the synthetic research of FLC materials for fast switching, we prepared 2-[4-[(/ )-2-fluorohexyloxy]phenyl]-5-[4-(5)-2-fluoro-2-methyldecanoyloxy]phenyl]-pyrimidine shown in Figure 2 and its diastereomers and homologs. 

Instead of perchlorates, tnfluoromethanesulfonates (Inflates) can be used They are readily prepared and claimed to be safer than perchlorates [75] F Aryl fluondes have been prepared from p YC6H4N" (CH3)3CF3S03- (Y = COCqHs, CN, CHO, NO2, COCH3, CO2C2H5) by this alternative substrate Fluorodequaternization can also be applied to the preparation of fluonnated heterocyclics such as 4 fluoro 6 phenyl 1,3 pyrimidine [76] (equation 15) and fluoropunnes [77]... 

Heating 6-bromo- and 6-chloro-2-halomethyl- (99JHC1065) and 6-bromo-, 6-chloro- and 6-fluoro-2-phenyl-4/f-pyrido[l, 2-u]pyrimidin-4-ones (00JMC2814) in phenyl ether at 220 °C for 10 min yielded the appropriate 7-halo-1,8-naphthyridin-4-ols. 6-Amino-2-trifluoromethyl-4//-pyrido[l, 2-a]-pyrimidin-4-one was transformed into 7-amino-2-trifluoromethyl-l,4-dihy-dro-l,8-naphthyridin-4-one in 90% yield (98EJM383). 

Pyrimidine 5-Fluoro-3-methyl-5-phenyl-trioxo-hexahydro- E10 (H — F)... 

Pyrimidine 6-Hydroxy-4-(penta-fluoro-ethyl)-2-phenyl- E9b/I, 55 (RF—CH = Cl — COOR + Benzamidine)... 

Palamanda, J.R., C.N. Casciano, L.A. Norton, R.P. Clement, F.V. Favreau, C.C. Lin et al. (2001). Mechemism-based inactivation of CYP2D6 by 5-fluoro-2-[4-[(2-phenyl-1 //-imidazol-5-yl)methyl]-l-piperazinyl]pyrimidine. Drug Metab. Dispos. 29, 863-867. 

Nagy LD, Mocny CS, Diffenderfer LE, Hsi DJ, Butler BF, Arthur EJ, Eletke KJ, Palamanda JR, Nomeir AA, Purge LL (2011) Substituted imidazole of 5-fluoro-2-[4-[(2-phenyl-177-imidazol-5-yl) methyl]-l-piperazinyl]pyrimidine inactivates cy-toehrome P450 2D6 by protein adduction. Drug Metab Dispos 39 974-983... 

Fluoro-lH-indol-3-yl)(phenyl)methyl)-l,3-dimethyl pyrimidine-2,4,6(17/,3//,5//)-... 

Electron-withdrawing and electron-donating groups on the pyridine moiety were compatible. It is worth noting that ster-ics and electronics play an inportant role in governing C2- vs. C6-selectivity for C3-substituted pyridines sterically hindered substrates, such as C3-pivalamido, phenyl, and ester substrates, preferred C6-arylation, whereas, due to electronic effects, C3-chloro- and fluoro-substrates favored C2-arylation. Other azines could also be cross-coupled with 2-methylthiophene including pyrimidine, quinoline, quinoxaline, pyridine, and pytidazine. 

Alkylamino)-6-aryl-3-phenyl-2-thioxo-2,3-dihydrothiazolo[4,5-d]pyrimidin-7(6H)-ones (I R = alkyl, substituted benzyl R1 = H, F) 141 were easily synthesized via a tandem aza-Wittig reaction. Treatment of iminophosphorane 139 with aromatic isocyanates gave carbodiimides 140 (same Rl), which reacted with fluoro-substituted alkylamines to provide the title compoimds 141 (Scheme 64) in 65-87% isolated yields using sodium ethoxide as catalyst [98],... 

---