Uses
5-Cyano-2-methylpyridine is used to synthesize acridone-based inhibitors of inosine 5'-monophosphate dehydrogenase (IMPDH). It is also used in the preparation of potent and selective nonpeptidic inhibitors of procollagen C-proteinase.This compound is suitable for pyruvate dehydrogenase (PDH) related research.
Synthesis
General procedure for the synthesis of 5-cyano-2-methylpyridine from 2-bromo-6-methylnicotinonitrile: a generalized method using Pd(OAc)2-PPh3, Pd2(dba)3-tbpf, Pd2(dba)3-DavePhos, Pd2(dba)3-P(t-Bu)3, Pd2(dba)3-XantPhos or Pd (OAc)2-XPhos as catalyst systems. First, anhydrous THF (13.2 mL) was degassed by bubbling argon for a few minutes, followed by the addition of Pd(OAc)2 (7.2 mg, 0.033 mmol, 5 mol%) and PPh3 (17.7 mg, 0.132 mmol, 20 mol%) and stirring of the resulting mixture for 30 minutes at room temperature. Next, halogenated heterocycles (0.66 mmol), TMEDA (0.130 g, 1.12 mmol, 1.7 eq.) and NaBH4 (42.4 mg, 1.12 mmol, 1.7 eq.) were added sequentially. The reaction mixture was stirred at room temperature or heated under argon protection at 65 °C for an appropriate time. After completion of the reaction, the residue was dissolved in brine and extracted with ethyl acetate. The organic phase was separated, dried and the solvent was evaporated, and finally the residue was purified by fast chromatography (using a mixture of petroleum ether and ethyl acetate) to give the pure hydrodehalogenated heterocyclic product.
References
[1] Tetrahedron Letters, 2010, vol. 51, # 12, p. 1562 - 1565
[2] Journal of Molecular Catalysis A: Chemical, 2014, vol. 393, p. 191 - 209
