2, 4-Dichloro-5-iodopyrimidine

Chemical Properties

Off-white powder

Uses

2,4-Dichloro-5-iodopyrimidine can be used as a reagent to synthesize dipeptidyl peptidase IV inhibitors. It is also used to synthesize pyrimidine VLA-4 antagonists.

Synthesis

The general procedure for the synthesis of 2,4-dichloro-5-iodopyrimidine from 5-iodouracil is as follows: 1. Preparation of intermediate 1: 2,4-dichloro-5-iodopyrimidine - To a suspension of N,N-dimethylaniline (11.0 mL) in 5-iodouracil (10.0 g, 42 mmol), phosphorus oxychloride (POCl3, 64.4 g, 39.2 mL, 420 mmol) was added. - The reaction mixture was heated to 90 °C and stirred at this temperature for 90 min. - After the reaction was completed, it was cooled to room temperature and the excess POCl3 was removed by evaporation. - The residue was slowly poured into an ice-water mixture and stirred for 2 h. The crystalline precipitate was collected by filtration and washed with cold water. - The crude product was dissolved in ethyl acetate and extracted sequentially with aqueous sodium bicarbonate and aqueous sodium sulfite. - The organic phase was dried with anhydrous sodium sulfate, filtered and the solvent was evaporated. - The residue was purified by column chromatography to afford 2,4-dichloro-5-iodopyrimidine (10.6 g, 92% yield). The structure of the product was determined by 1H-NMR. - The structure of the product was confirmed by 1H-NMR (400 MHz, CDCl3): δ 8.90 (s, 1H).

References

[1] Patent: EP1878726, 2008, A1. Location in patent: Page/Page column 32
[2] Patent: WO2007/71455, 2007, A1. Location in patent: Page/Page column 146
[3] Patent: US2007/232632, 2007, A1. Location in patent: Page/Page column 55; 56
[4] Patent: WO2008/155140, 2008, A1. Location in patent: Page/Page column 108
[5] Tetrahedron, 2000, vol. 56, # 27, p. 4777 - 4792