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

HRID 1407831Notes

Reaction equation

HRID 1407831 reaction equation
[CH3:1][O:2][C:3]1[C:8]([CH3:9])=[CH:7][C:6]2[C@:10]3([CH2:20][O:21][C:5]=2[CH:4]=1)[C:18]1[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=1)[NH:12][C:11]3=[O:19].[CH3:22][N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1.[CH2:29]=O>CO>[CH3:1][O:2][C:3]1[C:8]([CH3:9])=[CH:7][C:6]2[C@:10]3([CH2:20][O:21][C:5]=2[CH:4]=1)[C:18]1[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=1)[N:12]([CH2:22][N:23]1[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]1)[C:11]3=[O:19]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 531671-MethylpiperazineHCID 59352444(3S)-6-methoxy-5-methylspiro[1-benzofuran-3,3'-indol]-2'(1'H)-one

Product 1

HCID 59352312(3S)-6-methoxy-5-methyl-1'-[(4-methylpiperazin-1-yl)methyl]spiro[1-benzofuran-3,3'-indol]-2'(1'H)-oneYield 93%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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.

Workup

  1. concentrationThe solution was concentrated in vacuo to dryness
  2. dissolutiondissolved in methanol (5 mL)
  3. concentrationThe solution was again concentrated in vacuo to dryness
  4. dissolutiondissolved in distilled water (25 mL)
  5. customthe product was precipitated upon addition of 5 M NaOH (15 mL)
  6. filtrationThe solid was filtered
  7. customair dried

Sources & evidence

ORD record
ord-a825338580c349c0973e4d53e7d8e598
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

Loading…