Ammonia → 3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-5-carbonitrile

HRID 552922Notes

Reaction equation

HRID 552922 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[CH:6]2)#[N:2].[CH3:12][N:13]1[CH2:18][CH2:17][C:16](=O)[CH2:15][CH2:14]1.N1CCCC1.N>C(O)C.CO>[CH3:12][N:13]1[CH2:14][CH:15]=[C:16]([C:6]2[C:5]3[C:9](=[CH:10][CH:11]=[C:3]([C:1]#[N:2])[CH:4]=3)[NH:8][CH:7]=2)[CH2:17][CH2:18]1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 27513Indole-5-carbonitrileHCID 31268PyrrolidineHCID 740491-Methyl-4-piperidone

Product 1

HCID 149732163-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-5-carbonitrile

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 887MethanolSolvent

Procedure

To an argon-purged round bottom flask fitted with a magnetic stirbar containing an orange solution of 5-cyanoindole (48) (250 mg, 1.76 mmol) dissolved in absolute ethanol (10 mL) were added 1-methyl-4-piperidone (0.43 mL, 3.50 mmol) and pyrrolidine (0.44 mL, 5.27 mmol). The reaction vessel was fitted with a condenser and transferred to an oil bath preheated to 80° C. The reaction was stirred at this temperature for 44 hrs. As no starting material remained (TLC 5% 2M NH3 in methanol/95% CH2Cl2) the reaction was cooled to room temperature followed by additional cooling in the fridge. As no precipitate formed, the reaction was concentrated under reduced pressure to afford an orange oil. The oil was redissolved in ethanol (20 mL) and the solvent removed under reduced pressure. This was repeated once more, and then the final residue was treated with ethanol and left in the fridge for 2 hrs. The precipitate which formed was collected by vacuum filtration and washed with hexanes (205 mg of pale yellow solid, compound 49, 48.7%) 1H NMR (DMSO) δ 11.90 (br s, NH), 8.51 (s, 1H), 7.80 (s, 1H), 7.77-7.74 (d, J=8.7 Hz, 1H), 7.68-7.65 (d, J=8.1 Hz, 1H), 6.41 (s, 1H), 3.53 (s, 2H), 3.27-3.26 (d, J=2.4 Hz, 2H), 2.79-2.77 (d, J=4.5 Hz, 2H), 2.72-2.71 (d, J=1.5 Hz, 3H).

Workup

  1. customTo an argon-purged round bottom flask
  2. customfitted with a magnetic stirbar
  3. customThe reaction vessel was fitted with a condenser
  4. customtransferred to an oil bath
  5. custompreheated to 80° C
  6. temperatureby additional cooling in the fridge
  7. customAs no precipitate formed
  8. concentrationthe reaction was concentrated under reduced pressure
  9. customto afford an orange oil
  10. customthe solvent removed under reduced pressure
  11. additionthe final residue was treated with ethanol
  12. waitleft in the fridge for 2 hrs
  13. customThe precipitate which formed
  14. filtrationwas collected by vacuum filtration
  15. washwashed with hexanes (205 mg of pale yellow solid, compound 49, 48.7%) 1H NMR (DMSO) δ 11.90 (br s, NH), 8.51 (s, 1H), 7.80 (s, 1H), 7.77-7.74 (d, J=8.7 Hz, 1H), 7.68-7.65 (d, J=8.1 Hz, 1H), 6.41 (s, 1H), 3.53 (s, 2H), 3.27-3.26 (d, J=2.4 Hz, 2H), 2.79-2.77 (d, J=4.5 Hz, 2H), 2.72-2.71 (d, J=1.5 Hz, 3H)

Sources & evidence

ORD record
ord-085efe13e591402e898ad5d45045badf
Source dataset
uspto-grants-2011_05
Patent number
US07951940B2

Reaction notes

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