Methyl 2-(2,6-difluorophenyl)-1-[(2,6-difluorophenyl)methyl]benzimidazole-4-carboxylate → 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)benzimidazole-4-carbonitrile

Beteiligte Stoffe

Reaktionsschritte

To methyl 1-(2,6-difluorobenyl)-2-(2,6-difluorophenyl)benzimidazole-4-carboxylate (Example 102) (1.02 g, 2.46 mmol) suspended in xylene (60 mL) was added freshly prepared 1.0 M AlMe2NH2 (20 mL). After 3 h at reflux, the reaction was concentrated. The residue was redissolved in CH2Cl2 and washed with NaHSO4 (10% soln), NaHCO3 (sat. aq) and NaCl (sat. aq). The combined washings were dried (Na2SO4), filtered and concentrated. The crude product was purified by flash chromatography eluting with 2% methanol/CH2Cl2 and recrystallization from diethylether/hexane (3:1), yielding white crystals of 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)- benzimidazole-4-carbonitrile (1.72 g, 4.51 mmol, 61% yield). M.p. 156-157° C.; 1H NMR (200 MHz, CD2Cl2): δ7.76 (dd, J=1.0, 8.6 Hz, 1H, H5), 7.63 (dd, J=1.0, 7.6 Hz, 1H, H7), 7.58 (m, 1H, H4′), 7.37 (dd, J=7.6, 8.6 Hz, 1H, H6), 7.28 (m, 1H, H4″), 7.11 (m, 2H, H3′,5′), 6.83 (m, 2H, H3″,5″), 5.40 (s, 2H, CH2PhF2).

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