Acetic Acid → HCID 178527279, compound

Participants

Reaction Steps

A suspension of 3-(1-naphthylsulfonyl)-5-(piperidin-4-yloxy)-1H-indazole (53.9 mg, 0.132 mmol) in 1,2-dichloroethane was treated sequentially with phenylacetaldehyde (0.17 mL, 1.5 mmol) and acetic acid (1.7 mL, 3.0 mmol), stirred at ambient temperature for 1.5 hours, treated with sodium triacetoxyborohydride (66.9 mg, 0.316 mmol), stirred at ambient temperature for 3-19 hours, diluted with chloroform and washed with 1.0 N sodium hydroxide and brine. (Methanol was added to the organic phase to aid in solubility.) The organic phase was dried over anhydrous magnesium sulfate and concentrated in vacuo. The resultant residue was purified by flash chromatography using 0.1-0.5% ammonium hydroxide/1.0-5.0% methanol in chloroform to yield 3-(1-naphthylsulfonyl)-5-{[1-(2-phenylethyl)piperidin-4-yl]oxy}-1H-indazole as an orange foam (45.8 mg, 67.8%). The foam was dissolved in methanol and chloroform, treated with isopropanolic HCl and concentrated in vacuo for 13 hours at 86° C. to give the title product as an orange foam (43.4 mg); Mass spectrum (+EI, [M+H]+) m/z 512. 1HNMR (500 MHz, DMSO-d6): δ14.16 (d, 1H, J=4.52 Hz), 10.19-10.30 (m*, 1H), 8.70-8.76 (m, 1H), 8.56 (dd, 1H, J=7.32 Hz and 1.10 Hz), 8.27 (d, 1H, J=8.18 Hz), 8.04 (d, 1H, J=7.68 Hz), 7.70-7.75 (m, 1H), 7.55-7.63 (m, 3H), 7.10-7.39 (m*, 7H), 4.60-4.82 (m*, 1H), 3.60-3.65 (m, 1H), 3.38-3.45 (m, 1H), 3.30-3.36 (m*, 1H), 3.15-3.24 (m, 2H), 3.01-3.07 (m, 2H), 2.01-2.28 (m*, 3H), 1.80-1.95 ppm (m*, 1H). *Conformational isomers due to protonation of tertiary amine.

Provenance & Evidence