Aluminum(III) Chloride → 1h-Indol-3-yl-n-[6-(1-methylpiperidin-4-ylcarbonyl)-pyridin-2-yl]-carboxamide

HRID 30213Notes

Reaction equation

HRID 30213 reaction equation
[Cl-].[Cl-].[Cl-].[Al+3].C([N:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]([C:21]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([CH:32]3[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]3)=[O:31])[N:25]=2)=[O:22])=[CH:13]1)C1C=CC=CC=1>C1C=CC=CC=1.C(OCC)(=O)C>[NH:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]([C:21]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([CH:32]3[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]3)=[O:31])[N:25]=2)=[O:22])=[CH:13]1

Participants

5

Reactant 2

HCID 6451240Aluminum(III) Chloride2×HCID 597893621-Benzylindol-3-yl-n-[6-(1-methylpiperidin-4-ylcarbonyl)-pyridin-2-yl]-carboxamide

Product 1

HCID 597893601h-Indol-3-yl-n-[6-(1-methylpiperidin-4-ylcarbonyl)-pyridin-2-yl]-carboxamideYield 67%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Add aluminum trichloride (106 mg, 0.795 mmol) to a suspension of 1-benzylindol-3-yl-N-[6-(1-methylpiperidin-4-ylcarbonyl)-pyridin-2-yl]-carboxamide (180 mg, 0.398 mmol) in benzene (6 mL) and heat the mixture at reflux for 1.25 hr. Then add another 2 equivalents of aluminum trichloride (108 mg) and continue heating at reflux for an additional 5.5 hr. Cool the reaction mixture to room temperature. Then pour the reaction into ice cold H2O (50 mL) and then dilute with ethyl acetate. Adjusted the pH of the solution to 11 with saturated Na2CO3, separate the layers and extract the aqueous layer with ethyl acetate (3×50 mL). Combined the organic fractions, dry with Na2SO4, filter and concentrate in vacuo. Purify the intermediate by flash chromatography on a silica gel column, eluting with CHCl3/methanol/NH4OH (93:7:1) to obtain the sub-title compound (96 mg, 67%). 1H NMR (CD3OD) δ 8.45 (d, J=8 Hz, 1H), 8.25 (s, 1H), 8.21 (m, 1H), 7.96 (t, J=8 Hz, 1H), 7.72 (d, J=8 Hz, 1H), 7.48 (m, 1H), 7.18-7.27 (m, 2H), 3.90 (m, 1H), 2.94-3.01 (m, 2H), 2.31 (s, 3H), 2.19-2.28 (m, 2H), 1.92-2.02 (m, 2H), 1.71-1.84 (m, 2H). CIMS (Methane) m/z 363 [C21H22N4O2+H]+.

Workup

  1. temperatureheat the mixture
  2. temperatureat reflux for 1.25 hr
  3. temperaturecontinue heating
  4. temperatureat reflux for an additional 5.5 hr
  5. additionThen pour
  6. customAdjusted the pH of the solution to 11 with saturated Na2CO3, separate the layers
  7. extractionextract the aqueous layer with ethyl acetate (3×50 mL)
  8. dry with materialdry with Na2SO4
  9. filtrationfilter
  10. concentrationconcentrate in vacuo
  11. customPurify the intermediate by flash chromatography on a silica gel column
  12. washeluting with CHCl3/methanol/NH4OH (93:7:1)

Sources & evidence

ORD record
ord-341d13d4c0c54164a75c544356ddcb2c
Source dataset
uspto-grants-2008_09
Patent number
US07423050B2

Reaction notes

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