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

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.

1. temperatureThe mixture was then warmed to room temperature
2. stirringstirred for 2 hours
3. customThe reaction was quenched by the addition of water
4. extractionthe mixture was extracted by CH2Cl2 (3×100 ml)
5. washThe combined organic solvent was washed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. customthe solvent was evaporated in vacuo
9. customThe residue was purified by silica column chromatography (gradient: Heptane/EtOAc from 80/20 to 50/50)

ORD-Eintrag

ord-6206051bb87140c9a90a674b9b3acb97

Quelldatensatz

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08440701B2