Citric Acid → 4-(1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide citrate

HRID 2357453Notes

Reaction equation

HRID 2357453 reaction equation
[CH3:1][N:2]([CH3:34])[C:3]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:8][CH2:7][CH:6]([CH2:9][NH:10][C:11]([N:13]2[CH2:18][CH:17]=[C:16]([C:19]3[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[NH:21][CH:20]=3)[CH2:15][CH2:14]2)=[O:12])[CH2:5][CH2:4]1.C(O)C.[C:38]([OH:50])(=[O:49])[CH2:39][C:40]([CH2:45][C:46]([OH:48])=[O:47])([C:42]([OH:44])=[O:43])[OH:41]>C(Cl)Cl>[C:38]([OH:50])(=[O:49])[CH2:39][C:40]([CH2:45][C:46]([OH:48])=[O:47])([C:42]([OH:44])=[O:43])[OH:41].[CH3:1][N:2]([CH3:34])[C:3]1([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH2:4][CH2:5][CH:6]([CH2:9][NH:10][C:11]([N:13]2[CH2:14][CH:15]=[C:16]([C:19]3[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[NH:21][CH:20]=3)[CH2:17][CH2:18]2)=[O:12])[CH2:7][CH2:8]1

Participants

5

Reactant 3

HCID 311Citric AcidHCID 702EthanolHCID 593855634-(1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide

Product 1

HCID 675323514-(1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide citrate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The polar diastereoisomer of 4-(1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide (256 mg, 0.56 mmole) was dissolved in abs. ethanol (10 ml) and DCM (2 ml). Citric acid (108.8 mg, 0.57 mmole) was added in one portion at ca. 35° C. while stirring. After stirring for 4 hours at RT only brown droplets on the wall of the flask were visible. The supernatant solution was decanted and concentrated by evaporation in vacuo to ca. 5 ml. Diethyl ether (50 ml) was added in portions at RT. The precipitate formed was filtered off after 2 hours, washed with ether (2×3 ml) and dried in vacuo. The polar diastereoisomer of 4-(1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide citrate (222 mg, m.p. 125°-130° C., 61%, Example 22) was a pale brown solid.

Workup

  1. stirringAfter stirring for 4 hours at RT only brown droplets on the wall of the flask
  2. customThe supernatant solution was decanted
  3. concentrationconcentrated by evaporation in vacuo to ca. 5 ml
  4. additionDiethyl ether (50 ml) was added in portions at RT
  5. customThe precipitate formed
  6. filtrationwas filtered off after 2 hours
  7. washwashed with ether (2×3 ml)
  8. customdried in vacuo

Sources & evidence

ORD record
ord-c3559351a71d44d6a9eae01a19525fe7
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

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