Methyl iodide → 1-(2-Chloro-6-methyl-pyridine-4-carbonyl)-3-(3,4-difluoro-phenyl)-2-methyl-isothiourea

Participants

Reaction Conditions

Reaction Steps

A mixture of intermediate D1 (38 g; 111.4 mmol) in THF (400 ml) was cooled to 0° C. and NaH (60% pure) (6.7 g; 167 mmol) was carefully added. The reaction mixture was stirred for 15 minutes and then CH3I (14.2 g; 100 mmol) was added. The mixture was then warmed to room temperature and stirred for 2 hours. The reaction was quenched by the addition of water and then the mixture was extracted by CH2Cl2 (3×100 ml). The combined organic solvent was washed with brine, dried over MgSO4, filtered and the solvent was evaporated in vacuo. The residue was purified by silica column chromatography (gradient: Heptane/EtOAc from 80/20 to 50/50). Yield: 22.2 g of intermediate D2.

Provenance & Evidence