Hexahydro-1,4-diazepine → [4-[6-Amino-5-(5-phenyl-1,3,4-oxadiazol-2-yl)-3-pyridyl]phenyl]-(1,4-diazepan-1-yl)methanone

Participants

Reaction Steps

A solution of 4-(6-amino-5-(5-phenyl-1,3,4-oxadiazol-2-yl)pyridin-3-yl)benzoic acid (75.4 mg, 0.2104 mmol), carbonyl diimidazole (68.23 mg, 0.4208 mmol), DMAP (2.570 mg, 0.02104 mmol) and DIPEA (81.58 mg, 109.9 μL 0.6312 mmol) in DMSO (1.282 mL) was treated with 1,4-diazepane (63.22 mg, 0.6312 mmol) and the resulting solution stirred at ambient temperature for 16 hours. The reaction was treated with TBTU (67.56 mg, 0.2104 mmol) followed by 1,4-diazepane (63.22 mg, 0.6312 mmol) and DMF (1.282 mL) and allowed to stir at 60° C. for a further 48 hours. The reaction was treated with further TBTU (135.12 mg, (0.4208 mmol) and heated at 60° C. for a further 5 hours. The reaction mixture was diluted with EtOAc/water and the two layers separated. The organic layer was separated, dried (MgSO4), filtered and concentrated in vacuo. The resultant residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound (31 mg, 33% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.69 (s, 1H), 1.79 (s, 1H), 2.68 (s, 1H), 2.79-2.86 (m, 2H), 2.98 (t, J=4.9 Hz, 1H), 3.42 (dd, J=5.9, 12.8 Hz, 2H), 3.67 (d, J=5.3 Hz, 2H), 7.50 (dd, J=3.4, 7.9 Hz, 2H), 7.56 (s, 2H), 7.63-7.71 (m, 3H), 7.84 (q, J=3.9 Hz, 2H), 8.25-8.27 (m, 3H), 8.59 (d, J=2.3 Hz, 1H) and 8.66 (d, J=2.2 Hz, 1H) ppm; MS (ES+) 441.2.

Provenance & Evidence