Hydrochloric Acid → N-(6-methoxybenzo[d]thiazol-2-yl)-4'H-1-azaspiro[bicyclo[3.2.1]octane-6,5'-oxazol]-2'-amine

Participants

Reaction Conditions

Reaction Steps

((1R*,5S*,6S*)-(6-(aminomethyl)-6-hydroxy-1-ammoniobicyclo[3.2.1]octan-1-yl)trihydroborate (300 mg, 1.76 mmol) and N-(6-methoxybenzo[d]thiazol-2-yl)-1H-imidazole-1-carbothioamide (615 mg, 2.117 mmol) were combined in DMF (5 mL). The reaction was heated to 70° C. for 2 hours and then treated with N,N′-Diisopropylcarbodiimide (1.37 mL, 8.82 mmol). The reaction was then heated an additional 2 hours and cooled to room temperature. The reaction was poured into a chloroform/water mixture and the organic was collected and dried to a residue. The residue was taken up in acetone (6 ml) and treated with hydrochloric acid (3 mL, 3M, 9.00 mmol). The reaction was stirred at room temperature for 3 hours and then poured into a chloroform/water mixture. The organic was discarded and the water layer was neutralized to pH 7. The neutralized layer was extracted in chloroform and the chloroform was removed in vacco to give a crude mixture. This mixture was purified by PREP HPLC. The desired compound fractions were combined and diluted with saturated sodium bicarbonate. The solution was then extracted several times with chloroform. The chloroform layers were combined and concentrated to give N-(6-methoxybenzo[d]thiazol-2-yl)-4′H-1-azaspiro[bicyclo[3.2.1]octane-6,5′-oxazol]-2′-amine as a white powder (13.1.1 mg, 3%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 9.04-9.55 (m, 1H) 7.50 (d, J=8.78 Hz, 1H) 7.15 (d, J=2.51 Hz, 1H) 6.91 (dd, J=8.91, 2.64 Hz, 1H) 4.11 (d, J=9.79 Hz, 1H) 3.97-4.07 (m, 1H) 3.76-3.88 (m, 3H) 3.64 (d, J=14.31 Hz, 1H) 3.29 (br. s., 1H) 3.16 (d, J=14.31 Hz, 1H) 2.87-3.06 (m, 3H) 2.35 (d, J=2.76 Hz, 1H) 1.70-1.96 (m, 2H) 1.38-1.63 (m, 2H). MS: LC/MS RT=0.923 mins [M+H]=345.08.

Provenance & Evidence