2-phenoxyisonicotinonitrile synthesis

Yield:81249-44-7 95%

Reaction Conditions:

Stage #1: phenolwith caesium carbonate;N,N-dimethylethylenediamine at 20; for 0.5 h;
Stage #2: 2-chloro-4-pyridinenitrile at 80; for 2 h;

Steps:

83.3 Step 1: 2-phenoxyisonicotinonitrile (2)

A mixture of phenol (679 mg, 7.22 mmol), Cs2CO3 (3.53 g, 10.83 mmol), and DMA (10 mL)was stirred atRT for 30 mi 2-Chloro-4-pyridinecarbonitrile (1) (1.0 g, 7.22 mmol) was added and the mixture heated at 80 °C for 20 h. The mixture was cooled to RT and diluted with water (100 mL), brine (15 mL), and aq. 2M HC1 (15 mL). The mixture was extracted with EtOAc (2 x 50 mL) and the combined organic layers were dried (Mg504), filtered, and then concentrated under reduced pressure to afford compound 2 as a white solid (1.34 g, 95%) which did not require further purification. ‘H NMR (300 IVIFIz, DMSO-d6): 8.35 (m, 1H), 7.62 (m, 1H), 7.55 (m, 1H), 7.40-7.46 (m, 2H), 7.24 (m, 1H), 7.14-7.17 (m, 2H); LCMS Mass: 197.0 (M+1).

References:

WO2016/144702,2016,A1 Location in patent:Paragraph 00427