Ethanol → 8-[(4-methylpiperazin-1-yl)methyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 501222Notes

Reaction equation

HRID 501222 reaction equation
[NH:1]([C:3]1[CH:16]=[CH:15][C:6]([CH2:7][N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[CH:5][CH:4]=1)N.[CH2:17](O)[CH3:18]>>[CH3:14][N:11]1[CH2:12][CH2:13][N:8]([CH2:7][C:6]2[CH:15]=[CH:16][C:3]3[NH:1][C:5]4[CH2:4][CH2:3][NH:1][CH2:17][C:18]=4[C:4]=3[CH:5]=2)[CH2:9][CH2:10]1

Participants

3

Reactant 2

HCID 702EthanolHCID 684652221-(4-Hydrazinobenzyl)-4-methylpiperazine

Product 1

HCID 684652088-[(4-methylpiperazin-1-yl)methyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Conditions

Temperature
90 °C

Procedure

To a solution of 1-(4-hydrazinobenzyl)-4-methylpiperazine (3.4 g, 13.25 mmol) in ethanol (50 mL) were added piperidone. HCl (2.51 g, 18.55 mmol). The reaction temperature was raised to 90° C. and continued stirring for 2 hrs. The progress of the reaction was monitored by TLC and upon completion of the reaction the mixture was cooled to rt and HCl gas was bubbled through the reaction mixture at 0° C. After the reaction mixture was saturated with HCl, the temperature was raised to 90° C. again and continued stirring for 2 hrs. The ethanolic HCl was removed under reduced pressure and the pH of the reaction mixture was adjusted to 12.0 with 10% NaOH solution. The mixture was partitioned between 20% MeOH:DCM and water (35 mL) and the organic layer was separated, dried over Na2SO4 filtered and the solvent was removed under reduced pressure to give crude residue. Washing with ether gave 8-[(4-methylpiperazin-1-yl)methyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (1 g). 1H NMR (CD3OD, 200 MHz) δ: 7.31 (1H, s), 7.27 (1H, d, J=8.6 Hz), 7.06 (1H, d, J=8.6 Hz), 4.01 (2H, s), 3.60 (2H, s), 3.21 (8H, bm), 2.86 (4H, m), 2.28 (3H, s); m/e=285 (M+1).

Workup

  1. customThe progress of the reaction was monitored by TLC and upon completion of the reaction the mixture
  2. temperaturewas cooled to rt
  3. customHCl gas was bubbled through the reaction mixture at 0° C
  4. temperaturethe temperature was raised to 90° C. again
  5. stirringcontinued stirring for 2 hrs
  6. customThe ethanolic HCl was removed under reduced pressure
  7. customThe mixture was partitioned between 20% MeOH
  8. customDCM and water (35 mL) and the organic layer was separated
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. customthe solvent was removed under reduced pressure
  12. customto give crude residue
  13. washWashing with ether

Sources & evidence

ORD record
ord-eefb087144624bffb523f11f392cef0f
Source dataset
uspto-grants-2010_08
Patent number
US07772245B2

Reaction notes

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