Anisole → HCID 178527276, compound

Participants

Reaction Conditions

Reaction Steps

Triflic acid (1.6 mL, 18 mmol) was added to a solution of 3-[3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-pyrrolidine-1-carboxylic acid benzyl ester (1.35 g, 2.56 mmol) and anisole (0.83 mL, 7.7 mmol) in methylene chloride at 0° C. The reaction mixture was stirred at 0° C., under nitrogen, for 3.5 hours, treated with 2.5 N sodium hydroxide and extracted with warm ethyl acetate. The extracts were combined, washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The resultant residue was purified by flash chromatography with 0.5-1.0% ammonium hydroxide/5.0-10% methanol in chloroform to give 3-(naphthalene-1-sulfonyl)-5-(pyrrolidin-3-yloxy)-1H-indazole as a beige solid, 0.684 g (67.7% yield), mp 168-170° C. dec. A portion of the solid (110 mg) was treated with methanol and ethereal HCl; chloroform and more methanol were then added for better solubility. The resultant mixture was concentrated to dryness in vacuo at 82° C. for 12 hours to yield the title product as a cream-colored foam (0.108 g); Mass spectrum (+EI, [M+H]+) m/z 394. 1HNMR (500 MHz, DMSO-d6): δ14.15-14.28 (br, 1H), 9.21-9.45 (br, 2H), 8.74-8.76 (m, 1H), 8.56 (dd, 1H, J=7.32 Hz and 1.22 Hz), 8.27 (d, 1H, J=8.30 Hz), 8.02-8.04 (m, 1H), 7.71-7.75 (m, 1H), 7.55-7.64 (m, 3H), 7.29 (d, 1H, J=2.20 Hz), 7.11 (dd, 1H, J=9.15 Hz and 2.31 Hz), 5.19-5.21 (m, 1H), 3.43-3.47 (m, 1H), 3.28-3.34 (m, 2H), 2.16-2.25 (m, 1H), 2.04-2.10 ppm (m, 1H).

Provenance & Evidence