Methanol → HCID 49798444, compound

HRID 571564Notes

Reaction equation

HRID 571564 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.CO.[C:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1)(=[O:16])[CH3:15].N1CCCCC1>CC(O)=O>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](/[CH:10]=[CH:15]/[C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)=[O:16])=[CH:2]1

Participants

6

Reactant 4

HCID 887MethanolHCID 8082PiperidineHCID 10256Indole-3-CarboxaldehydeHCID 142862-Acetylpyridine

Product 1

HCID 49798444HCID 49798444, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Indole-3-carboxaldehyde (200 mg, 1.38 mmol) was added to a dried 100 mL round bottom flask under argon and anhydrous methanol (8 mL) was added. 2-Acetyl-pyridine (232 μL, 2.07 mmol) and piperidine (69 μL, 0.7 mmol) were added and the reaction was stirred under reflux for 24 hours, after which still no precipitate had formed (AcOH did not lead to precipitation). The crude reaction mixture was concentrated and directly applied to a silica column for chromatography (ethyl acetate:hexanes 1:1). The product was partially separated from the aldehyde starting material (some product coeluted with aldehyde and was discarded), and 80 mg (23%) of purified product was isolated. NMR: 1H NMR (600 MHz, d6-DMSO): δ 11.989 (s, 1H, N—H), 8.831-8.819 (m, pyr-H2), 8.220-8.194 (d, J=15.6, 1H, C═CH), 8.154-8.105 (m, 3H, C═CH, indole-H2, pyr-H3), 8.052-8.027 (m, 1H, pyr-H4), 7.976-7.962 (m, 1H, indole-H4), 7.679-7.656 (m, 1H, pyr-H5), 7.522-7.508 (m, 1H, indole-H7), 7.285-7.262 (m, 2H, indole-H5,6). 13C NMR (150 MHz, d6-DMSO): δ 188.2, 154.3, 149.1, 139.3, 137.7, 137.6, 134.2, 127.1, 125.1, 122.3, 122.2, 121.4, 120.1, 114.3, 113.1, 112.7. Melting Point: 141-145° C. TLC: (ethyl acetate:hexanes 4:1) Rf=0.40. Elemental analysis calculated for C16H12N2O.0.1C4H8O2: C, 76.62; H, 5.02; N, 10.90. found: C, 76.41; H, 5.03; N, 10.80.

Workup

  1. temperatureunder reflux for 24 hours
  2. customdid not lead to precipitation)
  3. customThe crude reaction mixture
  4. concentrationwas concentrated
  5. customThe product was partially separated from the aldehyde starting material (some product
  6. customwas isolated

Sources & evidence

ORD record
ord-65e4350509d4461b88ca45f83b91c3b4
Source dataset
uspto-grants-2015_05
Patent number
US09028796B2

Reaction notes

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