Dimethylformamide → HCID 86035944, compound

HRID 1678196Notes

Reaction equation

HRID 1678196 reaction equation
CN(C)[CH:3]=[O:4].P(Cl)(Cl)([Cl:8])=O.[N:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[N:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19][C:18]1=O>ClCCl.N1C=CC=CC=1>[Cl:8][C:18]1[N:17]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][N:11]=2)[C:25]2[C:20]([C:19]=1[CH:3]=[O:4])=[CH:21][CH:22]=[CH:23][CH:24]=2

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 20097216HCID 20097216, compound

Product 1

HCID 86035944HCID 86035944, compoundYield 23%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

The title compound is prepared following the procedure of Andreani, A. et al., J. Med. Chem. 20, (1977) 1344-1346 as follows. To a mixture of dimethylformamide (0.50 mL) and dichloromethane (0.50 mL) is added phosphorus oxychloride (0.50 mL) at 0° C. After stirring for 15 min, a solution of 1-(pyridin-2-yl)-1,3-dihydroindol-2-one (Le Baunt, G. et al., EP 0 580 502) (250 mg, 1.2 mmol) in dichloromethane (2.0 mL) and pyridine (0.25 mL) is added and the resulting dark-red solution is stirred for 36 hr. The reaction mixture is poured onto ice water and extracted with dichloromethane. The combined organic layer is washed with water, with saturated sodium bicarbonate, with brine, dried over sodium sulfate, filtered and concentrated. The dark residue is purified by chromatography eluting with dichloromethane-0 to 3% methanol. Product containing fractions are combined and concentrated to afford 2-chloro-1-(pyridin-2-yl)-1H-indole-3-carboxaldehyde (70 mg, 23% yield) as a beige solid. TLC (dichloromethane) Rf=0.18; ESI/MS 257 (M+H); RT=2.99 min; NMR 10.16 (1H, s); 8.79 (1H, d); 8.25 (2H, m); 7.84 (1H, d, J=9 Hz); 7.73 (1H, m); 7.40 (3H, m).

Workup

  1. customThe title compound is prepared
  2. stirringthe resulting dark-red solution is stirred for 36 hr
  3. additionThe reaction mixture is poured onto ice water
  4. extractionextracted with dichloromethane
  5. washThe combined organic layer is washed with water, with saturated sodium bicarbonate, with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe dark residue is purified by chromatography
  10. washeluting with dichloromethane-0 to 3% methanol
  11. additionProduct containing fractions
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-4bcc4d7998e245a7a6dc8ea91da1eccf
Source dataset
uspto-grants-2011_08
Patent number
US08008491B2

Reaction notes

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