Dimethylformamide → 2-Phenyl-1H-indole-3-carbaldehyde

HRID 966059Notes

Reaction equation

HRID 966059 reaction equation
P(Cl)(Cl)(Cl)=O.[C:6]1([C:12]2[NH:13][C:14]3[C:19]([CH:20]=2)=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.CN([CH:24]=[O:25])C>>[C:6]1([C:12]2[NH:13][C:14]3[C:19]([C:20]=2[CH:24]=[O:25])=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 136982-PhenylindoleHCID 24813Phosphorus oxychloride

Product 1

HCID 6133052-Phenyl-1H-indole-3-carbaldehyde

Conditions

Temperature
0 °C

Procedure

A mixture of DMF (11.0 mL, 142 mmol) and phosphorous oxychloride (3.63 mL, 39 mmol) is stirred at 0° C. for 1 h, a 0.2 mL portion is pipetted into a solution of 2-phenylindole (96 mg, 0.5 mmol) in DMF at 5° C. This reaction mixture is stirred at 5°-10° C. for 1 h, quenched with water, stored at −200 for 16 h and filtered. The filtercake is washed with water and dried in vacuo to afford the 2-phenylindole-3-carboxaldehyde intermediate. A suspension of the thus-obtained 2-phenylindole-3-carboxaldehyde (44.2 mg, 0.2 mmol) in isopropanol and concentrated HCl (50 μL) is treated with aminoguanidine bicarbonate (27 mg, 0.2 mmol), heated at 80° C. for 2 h, cooled to room temperature and concentrated in vacuo. The resultant residue is purified by HPLC to afford the title product, 28 mg (20% yield), identified by mass spectral and HPLC analyses (M+H) 277; retention time 3.76 min.

Workup

  1. stirringThis reaction mixture is stirred at 5°-10° C. for 1 h
  2. customquenched with water
  3. waitstored at −200 for 16 h
  4. filtrationfiltered
  5. washThe filtercake is washed with water
  6. customdried in vacuo

Sources & evidence

ORD record
ord-a10e1464a8ca41529c23b4f648bba226
Source dataset
uspto-grants-2005_10
Patent number
US06951881B2

Reaction notes

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