N,N-Dimethylaniline → HCID 86682420, compound

Participants

Reaction Steps

To a suspension of 2-methylnicotinic acid, 1 (274 mg, 2.0 mmol, 1 eq) in freshly distilled THF (5 mL) was added at −78° C. a solution of LDA (2.5 mL, 5.0 mmol, 2.5 eq) under Ar(g). The resulting purple solution was stirred at −78° C. for 30 min, and then warmed up to 0° C. for 1.5 h. The mixture was then cooled down to −78° C., and a solution of 2-chloro-4-dibenzylamino-benzonitrile, 2 (800 mg, 2.4 mmol, 1.2 eq) in THF (5 mL) was added. The reaction mixture was left to warm up to rt overnight, and was then quenched at 0° C. with H2O (20 mL), and extracted with CHCl3 (3×10 mL) and EtOAc (2×10 mL). The combined organic extracts were dried over MgSO4 and the solvent was removed in vacuo to give a crude pale red oil (1.15 g). To a solution of this residue in POCl3 (4.0 mL, 44 mmol, 22 eq) was added dimethylaniline (51 μL, 0.4 mmol, 0.20 eq). The mixture was refluxed at 100° C. under Ar(g) overnight; once cooled down, the solution was poured very slowly into a saturated Na2CO3 solution (50 mL) at 0° C., and was then partitioned and extracted with CH2Cl2 (3×20 mL). The combined organic extracts were dried over MgSO4 and the solvent was removed in vacuo. The residue was further purified by silica gel column chromatography with hexane/EtOAc (3:1-0:1) to yield an inseparable mixture of the product, 3, and the by-product benzyl-[3-chloro-4-(5-chloro-[1,6]naphthyridin-7-yl)-phenyl]-amine as a pale yellow oil (183 mg, 1:1 ratio; 3=10%, by-product=12% over 2 steps)

Provenance & Evidence