158626-15-4

6-(Bromomethyl)nicotinonitrile has been used as a reactant in the synthesis of oxadiazoles as selective S1P receptor agonists that may be used in the treatment of relapsing forms of MS.

Example 50 General procedure for the preparation of 6-bromomethylnicotinonitrile (11-2): to a solution of 6-methylnicotinonitrile (11-1) (15 g, 127 mmol) in carbon tetrachloride (300 mL) was added N-bromosuccinimide (27.12 g, 152.4 mmol). The reaction mixture was degassed and displaced three times with nitrogen, followed by the addition of AIBN (2,2'-azobisisobutyronitrile) (2.08 g, 12.6 mmol). After stirring the reaction at 85 °C for 7 h, AIBN (1.04 g) was added and the reaction was continued for 1 h. The reaction was completed with the addition of AIBN (2,2'-Azobisisobutyronitrile). After completion of the reaction, the solvent was removed by distillation under reduced pressure. The crude product was purified by silica gel column chromatography with the eluent being a mixed solvent of ethyl acetate/hexane to give 10 g of the target product 6-bromomethylnicotinonitrile in 40% yield.

[1] Patent: WO2007/28083, 2007, A2. Location in patent: Page/Page column 74-75
[2] Inorganic Chemistry, 2014, vol. 53, # 15, p. 7824 - 7836
[3] Patent: WO2016/201052, 2016, A1. Location in patent: Page/Page column 265
[4] Patent: WO2013/102145, 2013, A1. Location in patent: Paragraph 0351
[5] Patent: US2015/344483, 2015, A1. Location in patent: Paragraph 0649; 0650