Hydrochloric Acid → N-(4'-Amino-5'-methylspiro[chroman-4,2'-imidazole]-6-yl)-5-chloropicolinamide

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Reaction Steps

N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (58 mg, 0.30 mmol) was added to a suspension of 5-chloropyridine-2-carboxylic acid (37 mg, 0.23 mmol) in DCM (1.5 mL). The obtained solution was stirred for 10 min and added dropwise over 2 min to an ice-cooled solution of 5′-methylspiro[chroman-4,2′-imidazole]-4′,6-diamine (Intermediate 30, 54 mg, 0.23 mmol) and 2 M HCl (0.117 mL, 0.23 mmol) in DMF (1.5 mL). The mixture was stirred at 0° C. for 5 min. Volatiles were removed in vacuo, and the residue was purified by preparative chromatography. Fractions containing the product were combined, and the organic solvent was removed in vacuo. The aqueous residue was alkalized with (sat) NaHCO3 and then extracted twice with EtOAc. The combined organic phases were dried (Na2SO4) and evaporated to give a product which was purified by flash chromatography (4 g, gradient elution (EtOAc/MeOH/conc. NH3) in heptane) affording the title compound (27 mg, 31% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.92 (br. s., 2H), 2.23 (s, 3H), 4.23-4.54 (m, 2H), 6.56 (br. s., 2H), 6.80 (d, 1H), 7.05 (br. s., 1H), 7.54-7.72 (m, 1H), 8.04-8.12 (m, 1H), 8.13-8.23 (m, 1H), 8.72 (br. s., 1H), 10.41 (s, 1H); HPLC, MS (APCI+) m/z 370 [M+H]+.

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