Potassium Carbonate → 4'-((1S,2R)-2-{2-[(2R)-2-Methylpyrrolidin-1-yl]ethyl}cyclopropyl)-1,1'-biphenyl-4-carbonitrile

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Reaction Conditions

Reaction Steps

To a solution of the mesylate from Example 28G (methanesulfonic acid, 2-[(1R,2S)-2-(4′-cyano-biphenyl-4-yl)-cyclopropyl]-ethyl ester) and potassium carbonate in DMF was added (R)-2-methylpyrrolidine hydrobromide [CAS 117607-13-3]. The mixture was stirred at 50° C. overnight. The mixture was partitioned between ethyl acetate and H2O. The organic layer was washed with brine, dried (MgSO4), and concentrated in vacuo. The resulting residue was purified by chromatography on silica gel eluted with 7.5/20/70 MeOH/EtOAc/CH2Cl2 to provide the title compound. 1H NMR (300 MHz, CDCl3, free base): δ 0.88-1.0 (m, 2H), 1.18 (d, J=6 Hz, 3H), 1.4-2.4 (m, 11H), 2.9 (m, 1H), 3.15-3.23 (m, 1H), 7.15 (d, J=9 Hz, 2H), 7.47 (d, J=9 Hz, 2H), 7.66 (q, J=9 Hz, 4H). MS (DCl—NH3) m/z 331.2 (M+H)+. Anal, Calc. for C23H26N2.C4H6O6 1.25H2O (L-tartaric acid salt): C, 64.46; H, 6.91; N, 5.57. Found: C, 64.46; H, 6.91; N, 5.57.

Provenance & Evidence