Acetic Acid → HCID 178456297, compound

Participants

Reaction Steps

A solution of 3-(naphthalene-1-sulfonyl)-5-(pyrrolidin-3-yloxy)-1H-indazole (75.1 mg, 0.191 mmol) in methanol and chloroform was treated with ethereal HCl, concentrated, treated sequentially with 32 mL of 1,2-dichloroethane, propionaldehyde (0.55 mL, 7.6 mmol in two portions) and acetic acid (0.55 mL, 9.6 mmol in two portions). The reaction mixture was stirred, under nitrogen, at ambient temperatures for 2.5-3 hours, treated with sodium triacetoxyborohydride (81.2 mg, 0.384 mmol), stirred 1.5-20 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 magnesium sulfate and concentrated in vacuo. The resultant residue was purified by flash chromatography using 0.3-0.8% ammonium hydroxide/3.0-8.0% methanol in chloroform to yield 3-(naphthalene-1-sulfonyl)-5-(1-propyl-pyrrolidin-3-yloxy)-1H-indazole as a light yellow foam (43.8 mg, 52.5%). The foam was dissolved in methanol and chloroform, treated with isopropanolic HCl and concentrated in vacuo at 86° C. for 13 hours to give the title product as a light beige foam, 43.7 mg, Mass spectrum (+EI, [M+H]+) m/z 436. 1HNMR (500 MHz, DMSO-d6): δ14.20 (s, 1H), 10.29-10.62 (m*, 1H), 8.74 (d, 1H, J=8.54 Hz), 8.56 (d, 1H, J=6.95 Hz), 8.28 (d, 1H, J=8.30 Hz), 8.03-8.05 (m, 1H), 7.71-7.75 (m, 1H), 7.56-7.65 (m, 3H), 7.27 (s, 1H), 7.12 (dd, 1H, J=9.15 Hz and 2.32 Hz), 5.17-5.23 (m, 1H), 3.30-3.95 (m*, 3H), 3.11-3.23 (m*, 3H), 2.01-2.56 (m*, 2H), 1.60-1.69 (m, 2H), 0.87-0.90 ppm (m, 3H). *Conformational isomers due to protonation of tertiary amine.

Provenance & Evidence