5-Bromo-2-chloropyrimidine

Description

5-Bromo-2-chloropyrimidine is a pyrimidine compound that contains reactive groups bromine and chlorine atoms that are highly susceptible to chemical reactions. It is obtained by using 2-hydroxypyrimidine and hydrobromic acid as raw materials, catalytic heating reaction with hydrogen peroxide, and then purification treatment to obtain the intermediate; with the intermediate and chloride as raw materials, catalytic heating reaction using organic amine, and then purification is obtained. The chloride is phosphorus oxychloride; the organic amine is triethylamine or diisopropylethylamine or N,N-dimethylaniline or N,N-dimethylbenzylamine.

Chemical properties

Off-white to beige crystalline powder

The Uses of 5-Bromo-2-chloropyrimidine

5-Bromo-2-chloropyrimidine is applied as a pharmaceutical intermediate, in the synthesis of pharmaceutical goods such as inhibitors. It is also employed in the cross-coupling reactions of indium organometallics with 2,5-dihalopyrimidines.

Preparation

Under nitrogen protection, 35 g (0.2 mol) of 2-hydroxy-5-bromopyrimidine, 61.3 g (0.4 mol) of phosphorus oxychloride, and 200 mL of toluene were added into the reaction flask. At 35 ℃, triethylamine 40.5g was added and then heated up at 80-85 ℃. Stir the reaction for 6 hours, sampling HPLC to detect the raw material (less than 2%), and lower the temperature. After concentrating the mixture under reduced pressure to remove most of the toluene and Phosphorus oxychloride, put the reaction solution into 10°C water, and adjust pH=8-9 with 20% sodium carbonate aqueous solution. Finally, 5-Bromo-2-chloropyrimidine was obtained after purification.

Reactivity Profile

5-Bromo-2-chloropyrimidine, a 2,5-dihalopyrimidine, is a useful organic electrophiles. It could react with tri(3-indolyl)indium reagent through cross-coupling reaction. Other aryl- and heteroarylindium reagents, such as thiophenyl-, pyridyl-, naphthyl-, and alkynylindium reagents, also reacted with 5-bromo-2- chloropyrimidine to afford the corresponding 2-chloro-5-substituted pyrimidines[1].

References

[1] Mosquera A, et al. Cross-Coupling Reactions of Indium Organometallics with 2,5-Dihalopyrimidines: Synthesis of Hyrtinadine A?. Organic Letters, 2008; 10: 3745–3748.