Piperidine → HCID 12353122, compound

HRID 570622Notes

Reaction equation

HRID 570622 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=O)=[CH:2]1.[C:12]([C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1)(=[O:14])[CH3:13].N1CCCCC1.C(Cl)Cl.CO>CO>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](/[CH:10]=[CH:13]/[C:12]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)=[O:14])=[CH:2]1

Participants

6

Reactant 4

HCID 8082PiperidineHCID 95893-AcetylpyridineHCID 10256Indole-3-CarboxaldehydeHCID 21226129Dichloromethane methanol

Product 1

HCID 12353122HCID 12353122, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Indole-3-carboxaldehyde (100 mg, 0.69 mmol) was added to a dried 100 mL round bottom flask and dissolved in anhydrous methanol (5 mL). 3-Acetyl-pyridine (113 μL, 1.03 mmol, 1.5 equiv.) and piperidine (69 μL, 0.7 mmol) were added and the reaction stirred under reflux. After twelve hours, the reaction was cooled to room temperature, upon which a precipitate formed. The solid was filtered, yielding 54 mg. However, there was significant aldehyde present on a crude NMR. This mixture was dry-loaded onto silica and purified by column chromatography (methylene chloride:methanol 9:1), producing 33 mg pure, yellow solid (19%). NMR: 1H NMR (600 MHz, d6-DMSO): δ 12.004 (s, 1H, N—H), 9.292-9.289 (d, J=1.8, 1H, pyr-H2), 8.808-8.797 (dd, J1=4.8, J2=1.8, 1H, pyr-H6), 8.467-8.447 (dt, J1=7.8, J2=2.1, 1H, pyr-H4), 8.174 (s, 1H, indole-H2), 8.154-8.140 (dd, J1=6.6, J2=1.8, 1H, indole-H4), 8.120-8.095 (d, J=15.0, 1H, C═CH), 7.665-7.639 (d, J=15.6, 1H, C═CH), 7.607-7.585 (m, 1H, pyr-H5), 7.506-7.492 (dd, J1=6.9, J2=1.5, 1H, indole-H7), 7.268-7.223 (qd, J1=6.6, J2=1.5, 1H, indole-H5,6). 13C NMR (150 MHz, d6-DMSO): δ 187.9, 152.7, 149.3, 139.9, 137.6, 135.7, 134.1, 133.7, 125.1, 123.9, 122.9, 121.3, 120.7, 115.0, 112.9, 112.5. Melting Point: 192-194° C. TLC (methylene chloride:methanol 9:1) Rf=0.26. Elemental analysis calculated for C16H12N2O: C, 77.40; H, 4.87; N, 11.28. found: C, 77.00; H, 4.80; N, 11.12.

Workup

  1. temperatureunder reflux
  2. waitAfter twelve hours
  3. customformed
  4. filtrationThe solid was filtered
  5. customyielding 54 mg
  6. custompurified by column chromatography (methylene chloride:methanol 9:1)
  7. customproducing 33 mg pure

Sources & evidence

ORD record
ord-a5eceea888e649fcb889e7e4d51b0223
Source dataset
uspto-grants-2015_05
Patent number
US09023871B2

Reaction notes

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