Dicyclohexylcarbodiimide → 1H-Indole-3-carboxamide, 5-fluoro-2-methyl-N-(1-(phenylmethyl)-4-piperidinyl)-

HRID 2290202Notes

Reaction equation

HRID 2290202 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([CH3:11])=[C:5]2[C:12]([OH:14])=O.[NH2:15][CH:16]1[CH2:21][CH2:20][N:19]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:18][CH2:17]1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1>[CH2:22]([N:19]1[CH2:20][CH2:21][CH:16]([NH:15][C:12]([C:5]2[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=3)[NH:7][C:6]=2[CH3:11])=[O:14])[CH2:17][CH2:18]1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 4158521-Benzyl-4-piperidylamineHCID 135362755-fluoro-2-methyl-1H-indole-3-carboxylic acid

Product 1

HCID 30626671H-Indole-3-carboxamide, 5-fluoro-2-methyl-N-(1-(phenylmethyl)-4-piperidinyl)-Yield 74.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 16 g of 5-fluoro-2-methylindole-3-carboxylic acid in 260 ml of tetrahydrofuran were added 16 g of 4-amino-1-benzylpiperidine and 19 g of dicyclohexylcarbodiimide, and the whole mixture was refluxed under heating for 3 hours. After cooling, the precipitated dicyclohexylurea was filtered off and the extract was concentrated. A mixture of the residue in 70 ml of tetrahydrofuran was stirred at room temperature and the insoluble dicyclohexylurea was filtered off. The filtrate was concentrated and the resulting residue was crystallized with hexane. The resultant crystals were filtered with suction and recrystallized from ethyl acetate to give 22.5 g of N-(1-benzyl-4-piperidyl)-5-fluoro-2-methylindole-3-carboxamide, melting at 166°-169° C.

Workup

  1. temperaturethe whole mixture was refluxed
  2. temperatureunder heating for 3 hours
  3. temperatureAfter cooling
  4. filtrationthe precipitated dicyclohexylurea was filtered off
  5. concentrationthe extract was concentrated
  6. additionA mixture of the residue in 70 ml of tetrahydrofuran
  7. filtrationthe insoluble dicyclohexylurea was filtered off
  8. concentrationThe filtrate was concentrated
  9. customthe resulting residue was crystallized with hexane
  10. filtrationThe resultant crystals were filtered with suction
  11. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-9bb778fe7e9944459327a8dc48f6cce4
Source dataset
uspto-grants-1986_10
Patent number
US04616009

Reaction notes

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