2-Bromotoluene → 2'-Methyl-5-(4-methyl-piperazin-1-yl)-biphenyl-2-carboxylic acid methylamide

Temperature

-25 °C

To a solution of 125 mg (0.467 mmol) 2-chloro-N-methyl-4-(4-methyl-piperazin-1-yl)-benzamide and 0.22 ml (1.5 mmol) N,N,N′,N′-tetramethylethylenediamine in 2 ml THF a solution of o-tolyllithium, prepared by addition of 2.5 ml (3.8 mmol) of a 1.5 M solution of tert.-butyllithium in pentane to a solution of 0.23 ml (1.9 mmol) 2-bromotoluene in 2 ml diethyl ether at −78°, was added dropwise at −78°. The reaction mixture was allowed to warm to −25° C. over a period of 2 h. After quenching with 1 ml water at −25° the mixture was warmed to room temperature followed by dilution with 10 ml ethyl acetate and washing with 10 ml 1 N NaOH solution. The layers were separated and the aqueous layer was extracted with 2 10-ml portions of ethyl acetate. The combined organic layers were dried (Na2SO4) and evaporated. Chromatography (SiO2, CH2Cl2/methanol 19:1) afforded 55 mg (36%) 2′-Methyl-5-(4-methyl-piperazin-1-yl)-biphenyl-2-carboxylic acid methylamide as a colorless oil MS 5 (EI): 324 (M+).

1. additionwas added dropwise at −78°
2. customAfter quenching with 1 ml water at −25° the mixture
3. temperaturewas warmed to room temperature
4. washwashing with 10 ml 1 N NaOH solution
5. customThe layers were separated
6. extractionthe aqueous layer was extracted with 2 10-ml portions of ethyl acetate
7. dry with materialThe combined organic layers were dried (Na2SO4)
8. customevaporated

ORD record

ord-1e2e6d10d2a340c1976af3681ec6828a

Source dataset

uspto-grants-2003_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06552088B2