Cyanogen Bromide → 4-((1R,2S)-2-(2-(5-(methylsulfonyl)pyridin-2-yloxy)ethyl)cyclopropyl)piperidine-1-carbonitrile

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Reaction Steps

5-(Methylsulfonyl)-2-(2-((1S,2R)-2-(piperidin-4-yl)cyclopropyl)ethoxy)pyridine (Step A, Example 11; 310 mg, 0.957 mmol) and potassium carbonate (489 mg, 3.54 mmol) were stirred in chloroform (15 mL). Cyanogen bromide (122 mg, 1.15 mmol) was added. The mixture was stirred at RT for 15 min and refluxed overnight. The mixture was cooled to RT, mixed with silica gel (5 g), and concentrated to dryness under reduced pressure. The residue was loaded on a silica gel column (15 g of silica gel) and eluted with dichloromethane/methanol (99:1, 1 L to provide the title compound as an off-white solid. 1H NMR (300 MHz, CDCl3) δ 8.71 (dd, J=0.5, 2.5 Hz, 1H), 8.03 (dd, J=2.5, 8.7 Hz, 1H), 6.84 (dd, J=0.6, 8.7 Hz, 1H), 4.48 (t, J=7.2 Hz, 2H), 3.50-3.35 (m, 2H), 3.07 (s, 3H), 3.05-2.90 (m, 2H), 2.15-2.00 (m, 1H), 1.85-1.75 (m, 2H), 1.60-1.35 (m, 3H), 1.00-0.85 (m, 2H), 0.80-0.50 (m, 2H), −0.12 (q, J=5.0 Hz, 1H). MS (Multimode) m/z 339 [M+H]+.

Provenance & Evidence