Dimethylformamide → 3-(2-dimethylamino-ethyl)-1H-indole-5-carbaldehyde

HRID 71038

Reaction equation

HRID 71038 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][N:13]([CH3:15])[CH3:14].C([Li])(C)(C)C.CN([CH:24]=[O:25])C>CCOCC>[CH3:14][N:13]([CH3:15])[CH2:12][CH2:11][C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([CH:24]=[O:25])[CH:3]=2)[NH:7][CH:6]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 3602525-Bromo-N,N-DimethyltryptamineHCID 178418306HCID 178418306, compound

Product 1

HCID 99908943-(2-dimethylamino-ethyl)-1H-indole-5-carbaldehyde

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-75 °C

Procedure

To a solution of [2-(5-bromo-1H-indol-3-yl)-ethyl]-dimethyl-amine (Example 3) (15 g, 56.1 mmol) in ether (450 mL), at −75° C. a solution of tert-butyl lithium (99 ml of 1.7 N solution in hexanes, 168 mmol) is added. The mixture is stirred for 50 minutes at −75° C., and then for 30 minutes at −30° C. To the obtained beige suspension, DMF (22.5 ml) is added during 15 minutes, and then the mixture is allowed to warm to ambient temperature. The mixture is poured on water and extracted with diethyl ether (500 mL). After washing the organic layer with brine (3 times 500 mL), and drying (sodium sulfate), removal of the solvent leaves the crude aldehyde, which is recrystallized, from toluene/hexane. Yield of the title compound: 9.9 g (81.8%) yellowish plates, mp=103° C. 1H-NMR (CDCl3, 300 MHz) δ 2.36 (s, 6H, N(CH3)2); 2.65-2.75 (m, 2H, CH2); 2.96-3.03 (m, 2H, CH2NMe2); 7.08 (d, 1H, 3J=2.7 Hz, H-2); 7.33 (d, 1H, 3J=8.4 Hz, H-7); 7.70 (dd, 1H, 4J=1.7 Hz, H-6); 8.13 (d, 1H, H-4); 8.74 (br s, 1H, NH); 10.02 (s, 1H, CHO). 13C-NMR (CDCl3, 75 MHz) δ 23.91 (CH2); 45.76 (CH3); 60.40 (CH2N); 111.85 (C-7); 116.68 (C-3); 122.87 (C-6); 123.61 (C-2); 124.04 (C-4); 127.68 (C-9); 129.35 (C-5); 140.06 (C-8); 192.56 (CHO).

Workup

  1. waitfor 30 minutes at −30° C
  2. temperatureto warm to ambient temperature
  3. additionThe mixture is poured on water
  4. extractionextracted with diethyl ether (500 mL)
  5. washAfter washing the organic layer with brine (3 times 500 mL)
  6. customdrying
  7. custom(sodium sulfate), removal of the solvent

Sources & evidence

ORD record
ord-103c5592b2d34f4e8b4f57c3c31664ef
Source dataset
uspto-grants-2014_09
Patent number
US08822702B2

Linked notes

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