Hydrochloric Acid → N-(3-{[2-(4-Amino-1,2,5-oxadiazol-3-yl)-1-ethyl-1H-imidazo[4,5-c]pyridin-6-yl]oxy}phenyl)-4-[2-(morpholin-4-yl)ethoxy]benzamide

Participants

Reaction Conditions

Reaction Steps

Under argon, to a suspension of the HCl salt of 4-{[2-(4-morpholinyl)ethyl]oxy}benzoic acid (3.98 g, 13.8 mmol) in CH2Cl2 (100 ml) was added DMF (40 μl), followed with oxalylchloride (3.6 ml, 41.4 mmol). This mixture was then heated to reflux until a clear solution resulted. The reaction mixture was then concentrated, added CH2Cl2 (20 mL) and reconcentrated. A suspension of the above product in CH2Cl2 (100 mL), was added to a suspension of the product of Example 3 (3.96 g, 11.7 mmol) in pyridine (30 mL). This mixture was then heated to 70° C., the CH2Cl2 was distilled off, then stirred for 1 h. CH2Cl2 (200 mL) was added to the cooled reaction mixture, stirred for 15 min and then filtered to provide a first crop of product (crop 1). The filtrate was concentrated in vacuo and the residue taken up in EtOAc, washed with water (4×), brine, dried over Na2SO4, filtered and concentrated to provide Crop 2. Crops 1 and 2 were combined and recrystallized from MeOH to afforded a off white solid (5.54 g, 83%). 1H NMR (400 MHz, DMSO) δ ppm 11.35 (bs, 1H), 10.22 (s, 1H), 8.79 (d, 1H, 0.8 Hz), 7.99 (d, 2H, 8.8 Hz), 7.58-7.64 (m, 3H), 7.37 (t, 1H, 8.0 Hz), 7.12 (d, 2H, 8.8 Hz), 6.95 (s, 2H), 6.84-6.87 (m, 1H), 4.70 (q, 2H, 7.2 Hz), 4.53 (bs, 2H), 3.81-3.98 (m, 4H), 3.49-3.58 (m, 4H), 3.18-3.36 (m, 2H), 1.41 (t, 3H, 7.2 Hz). MS (ES+) m/e 571 [M+H]+.

Provenance & Evidence