Acetic Acid → HCID 178448512, compound

Participants

Reaction Steps

A suspension of 3-(1-naphthylsulfonyl)-5-(piperidin-4-yloxy)-1H-indazole (56.5 mg, 0.138 mmol) in 1,2-dichloroethane was treated sequentially with butyraldehyde (0.1 mL, 1 mmol) and acetic acid (0.1 mL, 2 mmol), stirred at ambient temperature for 3 hours, treated with sodium triacetoxyborohydride (46.5 mg, 0.220 mmol), stirred for 1 hour, 20 minutes under nitrogen at ambient temperatures, diluted with chloroform and poured into excess 1.0 N sodium hydroxide. The phases were separated. The organic phase was washed with brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The resultant residue was twice purified by flash chromatography using 0.25-0.5% ammonium hydroxide/2.5-5.0% methanol in chloroform to afford 5-(1-butylpiperidin-4-yloxy)-3-(1-naphthylsulfonyl)-1H-indazole as a light orange foam, 25.6 mg (40.0% yield). The foam was dispersed in methanol, treated with ethereal HCl and concentrated in vacuo at 83° C. for 25 hours to give the title product as an orange foam, 22.0 mg, Mass spectrum (+EI, [M+H]+) m/z 464. 1HNMR (500 MHz, DMSO-d6): δ14.16 (d, 1H, J=4.15 Hz), 9.86-9.98 (m*, 1H), 8.73 (dd, 1H, J=15.74 Hz and 8.42 Hz), 8.54-8.56 (m, 1H), 8.27 (d, 1H, J=8.29 Hz), 8.02-8.05 (m, 1H), 7.70-7.75 (m, 1H), 7.54-7.63 (m, 3H), 7.28-7.38 (s* and s*, 1H), 7.09-7.20 (m*, 1H), 4.60-4.80 (m*, 1H), 3.52-3.55 (m, 1H), 3.32-3.35 (m, 1H), 3.00-3.16 (m, 4H), 2.06-2.16 (m, 2H), 1.97-2.00 (m, 1H), 1.79-1.88 (m, 1H), 1.60-1.67 (m, 2H), 1.25-1.34 (m, 2H), 0.92-0.87 ppm (m, 3H). *Conformational isomers due to protonation of tertiary amine.

Provenance & Evidence