Formaldehyde → (3S)-6-methoxy-5-methyl-1'-[(4-methylpiperazin-1-yl)methyl]spiro[1-benzofuran-3,3'-indol]-2'(1'H)-one

Participants

Reaction Steps

A stirred solution of (3S)-6-methoxy-5-methylspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one (0.50 g, 1.8 mmol), N-methylpiperazine (1.80 g, 17.8 mmol) and formaldehyde (37% wt solution in water, 1.45 mL, 17.8 mmol) in methanol was refluxed for 3 h. The solution was concentrated in vacuo to dryness and dissolved in methanol (5 mL) and hydrochloric acid saturated methanol (10 mL). The solution was again concentrated in vacuo to dryness, dissolved in distilled water (25 mL) and the product was precipitated upon addition of 5 M NaOH (15 mL). The solid was filtered and air dried to afford (3S)-6-methoxy-5-methyl-1′-[(4-methylpiperazin-1-yl)methyl]spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one (0.65 g, 93%). To a stirred solution of the above product (0.20 g) in methanol (1 mL) was added hydrochloric acid saturated methanol (2 mL). The solution was stirred for 20 min, then diethyl ether (25 mL) was added and the suspension was filtered and air dried to afford (3S)-6-methoxy-5-methyl-1′-[(4-methylpiperazin-1-yl)methyl]spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one hydrogen chloride (0.19 g, 71%) as a colorless solid: mp>200° C. (dec.); 1H NMR (300 MHz, CDCl3) δ7.71 (s, 2H), 7.42 (d, J=7.9 Hz, 1H), 7.33 (dd, J=7.5, 7.5 Hz, 1H), 7.17-7.03 (m, 2H), 6.69 (s, 1H), 6.62 (s, 1H), 4.89-4.70 (m, 2H), 4.65 (d, J=9.40 Hz, 1H), 3.77 (s, 3H), 3.52-2.91 (m, 5H), 2.72 (s, 3H), 1.98 (s, 3H); MS (ES+) m/z 394.0 (M+1); Anal. Calcd. for C23H27N3O3.2.5HCl.2.5H2O: C, 52.15; H, 6.57; N, 7.93. Found: C, 52.07; H, 6.32; N, 8.50.

Provenance & Evidence