2-Bromopyridine → (4-Cyclobutyl-piperazin-1-yl)-(6-pyridin-2-yl-6-aza-spiro[2.5]oct-1-yl)-methanone

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(4-cyclobutylpiperazin-1-yl)(6-azaspiro[2.5]octan-1-yl)methanone (100 mg, 0.36 mmol), Sodium tert-butoxide (34.6 mg, 0.36 mmol) and 2-bromopyridine (62.7 mg, 0.40 mmol) were weighted in a microwave vial. A solution of Palladium(II) acetate (4.05 mg, 0.02 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (X-Phos) (8.59 mg, 0.02 mmol) in toluene (3.75 mL) and tert-butanol (0.75 mL)was added and the mixture heated at 160 °C for 10 minutes, and then 20 minutes more. The mixture was evaporated to dryness, redissolved in a minimum of methanol, filtered and purified on preparative HPLC using the long high pH (acetonitrile in water ammonium carbonate buffer, 25 min.) 20 to 40% gradient method on XBridge Prep C18 OBD, 30x150 mm, 5 mm, Waters reverse phase column, giving (4-cyclobutylpiperazin-1-yl)(6-(pyridin-2-yl)-6-azaspiro[2.5]octan-1-yl)methanone (34.0 mg, 26.6 %) as a slightly yellow solid after lyophilization. 1H NMR (400 MHz, DMSO- _d_ 6) d ppm 0.75 (dd, _J_ =7.81, 3.91 Hz, 1 H) 1.06 (t, _J_ =4.49 Hz, 1 H) 1.31 - 1.67 (m, 6 H) 1.74 (d, _J_ =10.16 Hz, 2 H) 1.85 - 2.00 (m, 3 H) 2.01 - 2.36 (m, 4 H) 2.65 (quin, _J_ =7.52 Hz, 1 H) 3.35 - 3.69 (m, 8 H) 6.58 (dd, _J_ =6.64, 5.08 Hz, 1 H) 6.82 (d, _J_ =8.59 Hz, 1 H) 7.49 (td, _J_ =7.81, 1.95 Hz, 1 H) 8.08 (dd, _J_ =4.88, 1.37 Hz, 1 H) HRMS _m_ / _z_ calcd for C21H31N4O [M + H]+ 355.24924, found 355.24965.

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