3-Bromopyridine → (4-Cyclobutylpiperazin-1-yl)-(7-pyridin-3-yl-7-azaspiro[3.5]nonan-2-yl)methanone

Participants

Reaction Conditions

Reaction Steps

cesium carbonate (123 mg, 0.38 mmol) was added to a solution of (4-cyclobutylpiperazin-1-yl)(7-azaspiro[3.5]nonan-2-yl)methanone (100 mg, 0.34 mmol), PdOAc2 (7.70 mg, 0.03 mmol), BINAP (42.7 mg, 0.07 mmol) and 3-bromopyridine (56.9 mg, 0.36 mmol) in toluene (2 mL). The reaction mixture was heated to 110°C for 18hrs. The room temperature cooled down mixture was filtered over celite. The solvent was concentrated. The product was purified by preparative HPLC using a low pH shallow gradient method (Mobile phase: 20-40% B; A: H2O with 0.05% TFA , B: CH3CN, 25 min. run) on Luna 15 m, C8 (2), 21.2x250 mm Phenomenex reverse phase column to provide (4-cyclobutylpiperazin-1-yl)(7-(pyridin-3-yl)-7-azaspiro[3.5]nonan-2-yl)methanone (10.00 mg, 7.91 %) as white solid. 1H NMR (400 MHz, CHLOROFORM- _d_ ) d ppm 1.58 (s, 3 H) 1.63 (dd, _J_ =6.25, 4.69 Hz, 2 H) 1.66 - 1.79 (m, 3 H) 1.80 - 1.94 (m, 2 H) 1.97 - 2.10 (m, 3 H) 2.12 - 2.21 (m, 2 H) 2.27 (q, _J_ =5.60 Hz, 3 H) 2.71 (quin, _J_ =7.91 Hz, 1 H) 3.21 (quin, _J_ =8.79 Hz, 1 H) 3.32 - 3.39 (m, 2 H) 3.41 (dd, _J_ =6.64, 4.69 Hz, 2 H) 3.54 (dd, _J_ =6.25, 4.69 Hz, 2 H) 3.63 (t, _J_ =4.88 Hz, 2 H) 6.53 - 6.60 (m, 1 H) 6.65 (d, _J_ =8.59 Hz, 1 H) 7.40 - 7.48 (m, 1 H) 8.16 (td, _J_ =2.34, 1.17 Hz, 1 H) HRMS _m/z_ calcd for C22H32N4O 369.26489 [M+H]+, found 369.26533. MS _m/z_ 369.2 [M+H]\+ (ES+)

Provenance & Evidence