Lithium hexamethyldisilazane → 2,6-Difluoro-N-{1-[(2-methyl-4-nitrophenyl)methyl]-1H-pyrazol-3-yl}benzamide

To a solution of 2,6-difluoro-N-(1H-pyrazol-3-yl)benzamide (for a preparation see Intermediate 9)(1.5 g, 6.72 mmol) in THF (30 ml) at ambient temperature under nitrogen was added 1.0 M lithium bis(trimethylsilyl)amide in THF (6.5 ml, 6.50 mmol, Aldrich). The solution was stirred for 30 min. To the solution was added a solution of 1-(bromomethyl)-2-methyl-4-nitrobenzene (1.5 g, 6.52 mmol) in THF (20 ml). The resulting pale orange solution was stirred at ambient temperature under nitrogen over the weekend. The solvent was evaporated in vacuo and the residue partitioned between ethyl acetate (150 ml) and saturated aqueous sodium hydrogen carbonate (50 ml). The phases were separated and the aqueous layer washed with ethyl acetate (25 ml). The combined organic phases were dried (MgSO4), filtered and the solvent removed in vacuo to leave a yellow oil (2.87 g). The sample was loaded in dichloromethane and purified on silica 100 g using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white foam (1.6 g); LCMS: (System 4) MH+=373, tRET=2.65 min.

1. customat ambient temperature
2. stirringThe resulting pale orange solution was stirred at ambient temperature under nitrogen over the weekend
3. customThe solvent was evaporated in vacuo
4. customthe residue partitioned between ethyl acetate (150 ml) and saturated aqueous sodium hydrogen carbonate (50 ml)
5. customThe phases were separated
6. washthe aqueous layer washed with ethyl acetate (25 ml)
7. dry with materialThe combined organic phases were dried (MgSO4)
8. filtrationfiltered
9. customthe solvent removed in vacuo

ORD record

ord-c022acd938ca4ac59de941a379368105

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399436B2