Formaldehyde → HCID 178480496, compound

Participants

Reaction Steps

A suspension of 3-(1-naphthylsulfonyl)-5-(piperidin-4-yloxy)-1H-indazole (57.7 mg, 0.142 mmol) in acetonitrile was treated in three portions with odium triacetoxyborohydride (54 mg, 0.26 mmol) and 37% formaldehyde in water (0.1 mL, 1.3 mmol), stirred at ambient temperatures for 2.5 hours and poured into excess chloroform and 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 purified by flash chromatography with 0.5% ammonium hydroxide/5.0% methanol in chloroform to give 5-(1-methylpiperidin-4-yloxy)-3-(1-naphthylsulfonyl)-1H-indazole (47.9 mg, 0.144 mmol) as a light orange foam. The foam was dispersed in methanol and chloroform, treated with isopropanolic HCl and concentrated in vacuo at 82° C. in for 10 hours to yield the title product as a light orange solid, mp 252-4° C.; Mass spectrum (+EI, [M+H]+) m/z 422. 1HNMR (300 MHz, DMSO-d6): δ14.16 (s, 1H), 10.06-10.17 (m*, 1H), 8.73-8.75 (m, 1H), 8.54-8.56 (m, 1H), 8.26-8.28 (m, 1H), 8.02-8.05 (m, 1H), 7.72 (t, 1H, J=7.81 Hz), 7.55-7.63 (m, 3H), 7.29-7.37 (m*, 1H), 7.10-7.20 (m*, 1H), 4.58-4.77 (m*, 1H), 3.45-3.50 (m, 1H), 3.07-3.20 (m, 2H), 2.75 (s, 3H), 1.70-2.20 ppm (m*, 4H). *Conformational isomers due to protonation of tertiary amine.

Provenance & Evidence