1-(chloromethyl)-3-[[6-[2-(dimethylamino)ethoxy]-5-methoxyindol-2-yl]carbonyl]-5-nitro-1,2-dihydro-3H-benz[e]indole → 5-amino-1-(chloromethyl)-3-[[6-[2-(dimethylamino)ethoxy]-5-methoxyindol-2-yl]carbonyl]-1,2-dihydro-3H-benz[e]indole

HRID 366819Notes

Reaction equation

HRID 366819 reaction equation
[Cl:1][CH2:2][CH:3]1[C:11]2[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[C:8]([N+:16]([O-])=O)=[CH:7][C:6]=2[N:5]([C:19]([C:21]2[NH:22][C:23]3[C:28]([CH:29]=2)=[CH:27][C:26]([O:30][CH3:31])=[C:25]([O:32][CH2:33][CH2:34][N:35]([CH3:37])[CH3:36])[CH:24]=3)=[O:20])[CH2:4]1>C1COCC1.O=[Pt]=O>[NH2:16][C:8]1[C:9]2[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=2[C:11]2[CH:3]([CH2:2][Cl:1])[CH2:4][N:5]([C:19]([C:21]3[NH:22][C:23]4[C:28]([CH:29]=3)=[CH:27][C:26]([O:30][CH3:31])=[C:25]([O:32][CH2:33][CH2:34][N:35]([CH3:37])[CH3:36])[CH:24]=4)=[O:20])[C:6]=2[CH:7]=1

Participants

4

Reactant 1

HCID 104144181-(chloromethyl)-3-[[6-[2-(dimethylamino)ethoxy]-5-methoxyindol-2-yl]carbonyl]-5-nitro-1,2-dihydro-3H-benz[e]indole

Product 1

HCID 3951845-amino-1-(chloromethyl)-3-[[6-[2-(dimethylamino)ethoxy]-5-methoxyindol-2-yl]carbonyl]-1,2-dihydro-3H-benz[e]indole

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 14f (130 mg, 0.25 mmol) in THF (20 mL) was hydrogenated over PtO2 (30 mg) at 55 psi for 2 h. The catalyst was removed and the solution was concentrated under reduced pressure below 30° C. The residue was dissolved in a small volume of CH2Cl2, the solution was diluted with petroleum ether to precipitate impurities which were removed by filtration, and then further addition of petroleum ether precipitated 15f (87 mg, 71%), mp 130-133° C. 1H NMR [(CD3)2SO] δ 11.38 (d, J=1.6 Hz, 1 H, NH), 8.07 (d, J=8.5 Hz, 1 H, H-6), 7.75 (d, J=8.3 Hz, 1 H, H-9), 7.72 (s, 1 H, H-4), 7.45 (t, J=7.4 Hz, 1 H, H-8), 7.27 (t, J=7.7 hz, 1 H, H-7), 7.15 (s, 1 H, H-3'), 7.05 (s, 1 H, H-4' or 7'), 6.99 (s, 1 H, H-4' or 7'), 5.96, 5.94 (2×s, 2 H, NH2), 4.71 (dd, J=10.6, 9.1 Hz, 1 H, H-2), 4.50 (dd, J=10.9 Hz, 1.6 Hz, 1 H, H-2), 4.16-4.08 (m, 1 H, H-1), 4.05 (t, J=6.0 Hz, 2 H, OCH2), 3.98 (dd, J=11.0, 3.0 Hz, 1 H, CHHCl), 3.79 (s, 1 H, OCH3), 3.74 (dd, J=10.9, 8.2 Hz, 1 H, CHHCl), 2.68 (t, J=5.9 Hz, 2 H, OCH2CH2), 2.25 (s, 6 H, N(CH3)2).

Workup

  1. customThe catalyst was removed
  2. concentrationthe solution was concentrated under reduced pressure below 30° C
  3. dissolutionThe residue was dissolved in a small volume of CH2Cl2
  4. additionthe solution was diluted with petroleum ether
  5. customto precipitate impurities which
  6. customwere removed by filtration
  7. additionfurther addition of petroleum ether
  8. customprecipitated 15f (87 mg, 71%), mp 130-133° C

Sources & evidence

ORD record
ord-d8f4f8eac9f140759d55219eb948b878
Source dataset
uspto-grants-2000_10
Patent number
US06130237

Reaction notes

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