3-(2-dimethylamino-ethyl)-1H-indole-5-carbaldehyde → HCID 68472493, compound

HRID 507375Notes

Reaction equation

HRID 507375 reaction equation
[CH3:1][N:2]([CH3:16])[CH2:3][CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([CH:14]=O)[CH:12]=2)[NH:7][CH:6]=1.[CH2:17]([O:21][C:22]([NH:24][NH2:25])=[O:23])[CH:18]([CH3:20])[CH3:19]>CO>[CH2:17]([O:21][C:22]([NH:24][N:25]=[CH:14][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:4][CH2:3][N:2]([CH3:16])[CH3:1])=[O:23])[CH:18]([CH3:20])[CH3:19]

Participants

4

Reactant 2

HCID 99908943-(2-dimethylamino-ethyl)-1H-indole-5-carbaldehydeHCID 18779866Hydrazinecarboxylic acid isobutyl ester

Product 1

HCID 68472493HCID 68472493, compoundYield 85.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 100 ml flask is charged with 3-(2-dimethylamino-ethyl)-1H-indole-5-carbaldehyde (Reference Example 9; 2.16 g, 10 mmol), methanol (50 ml), and hydrazinecarboxylic acid isobutyl ester (1.32 g, 10 mmol). This mixture is heated at reflux, and after 6 hours the conversion is 70% by NMR. Heating is continued over night, and removal of the solvent gives the crude product, which is then filtered over a pad of silica (40 g) with the following eluent: CH2Cl2:methanol: NEt3 90:10:1 (v:v:v), ca. 700 ml. Removal of the solvent gives the product (2.82 g, 85%) as a pale yellow residue which is pure by NMR. 1H-NMR (CDCl3, 300 MHz) δ 0.93 (d, 6H, J=6.5 Hz, CH(CH3)2); 1.96 (m, 1H, CH(CH3)2); 2.22 (s, 6H, N(CH3)2); 2.52, 2.78 (2 m, 2H each, CH2CH2NHMe2); 3.97 (d, 2H, J=6.5 Hz, OCH2); 6.85 (s, 1H, H-2); 7.04 (d, 1H, J=7.6 Hz, H-7); 7.41 (dd, 1H, J=1.5 Hz, H-6); 7.61 (bs, 1H, H-4); 7.86 (br s, 1H, N═CH); 9.43 (br s, 1H, NH); 9.82 (br s, 1H, H-1). 13C-NMR (CDCl3, 75 MHz) δ 19.36 (CH(CH3)2); 23.59 (CH2); 28.39 (CH(CH3)2); 45.53 (N(CH3)2); 60.32 (CH2NMe2); 71.87 (OCH2); 112.20 (C-7); 114.21 (C-3); 119.35 (C-4); 120.58 (C-6); 123.41 (C-2); 125.17 (C-5); 127.48 (C-9); 137.76 (C-8); 146.80 (N═CH); 154.91 (NC═O).

Workup

  1. temperatureThis mixture is heated
  2. temperatureat reflux
  3. temperatureHeating
  4. waitis continued over night
  5. customremoval of the solvent
  6. customgives the crude product, which
  7. filtrationis then filtered over a pad of silica (40 g) with the following eluent
  8. customRemoval of the solvent

Sources & evidence

ORD record
ord-a267af5a2a8d47b9b5e7b834df17ce92
Source dataset
uspto-grants-2010_08
Patent number
US07786156B2

Reaction notes

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