Diisopropylamine → (5-bromo-2-fluoro-pyridin-3-yl)-(2-ethyl-2H-pyrazol-3-yl)-methanone

Diisopropylamine and tetrahydrofuran were combined and cooled to −20° C. n-Butyl lithium (2.5M in hexanes) was slowly added and the resulting mixture stirred at this temperature for 30 minutes. The temperature was lowered to −78° C. and neat 5-bromo-2-fluoropyridine was added (internal temperature was not allowed to exceed −68° C.). The reaction mixture was stirred at −78° C. for 40 minutes. The resulting mixture was added to a solution of 2-ethyl-2H-pyrazole-3-carboxylic acid methoxy-methyl-amide in tetrahydro-furan. The combined reaction mixture was stirred at −78° C. for 1 hour before the reaction mixture was slowly warmed to room temperature, and quenched with saturate aqueous ammonium chloride solution. The reaction mixture was extracted with dichloromethane, dried over sodium sulfate, and concentrated. The crude material was purified by flash chromatography on silica gel to afford (5-bromo-2-fluoro-pyridin-3-yl)-(2-ethyl-2H-pyrazol-3-yl)-methanone. MS: m/z 298.1+300.1 (M+H+).

1. additionwas slowly added
2. customwas lowered to −78° C.
3. customto exceed −68° C.
4. stirringThe reaction mixture was stirred at −78° C. for 40 minutes
5. customThe combined reaction mixture
6. stirringwas stirred at −78° C. for 1 hour before the reaction mixture
7. customquenched with saturate aqueous ammonium chloride solution
8. extractionThe reaction mixture was extracted with dichloromethane
9. dry with materialdried over sodium sulfate
10. concentrationconcentrated
11. customThe crude material was purified by flash chromatography on silica gel

ORD record

ord-31f4e9a350f644cd9a215d7ab87e70c9

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07709645B2