5-Methoxy-3-(piperidin-4-yl)-1H-indole → HCID 10484698, compound

HRID 2357481Notes

Reaction equation

HRID 2357481 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C1([O:24][C:25](=O)[NH:26][CH2:27][CH:28]2[CH2:33][CH2:32][C:31]([N:40]([CH3:42])[CH3:41])([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH2:30][CH2:29]2)C=CC=CC=1>O1CCOCC1>[CH3:41][N:40]([CH3:42])[C:31]1([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:32][CH2:33][CH:28]([CH2:27][NH:26][C:25]([N:15]2[CH2:16][CH2:17][CH:12]([C:6]3[C:5]4[C:9](=[CH:10][CH:11]=[C:3]([O:2][CH3:1])[CH:4]=4)[NH:8][CH:7]=3)[CH2:13][CH2:14]2)=[O:24])[CH2:29][CH2:30]1

Participants

4

Reactant 2

HCID 432245-Methoxy-3-(piperidin-4-yl)-1H-indoleHCID 67531743(4-Dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid phenyl ester

Product 1

HCID 10484698HCID 10484698, compoundYield 30.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

In each case 5-methoxy-3-piperidine-4-yl-1H-indole (169.3 mg, 0.735 mmole) in dioxane (4.5 ml) and the diastereoisomer mixture of (4-dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid phenyl ester (259.0 mg, 0.735 mmole) were dissolved in two microwave reaction vessels. The reaction mixture was treated with microwave radiation as follows: experiment 1 (150° C., 52 minutes) and experiment 2 (200° C., 2 minutes). In each experiment the reaction mixture was worked up by distilling off the solvent in vacuo. The respective residue contained, apart from phenol, also the two diastereomers of 4-(5-methoxy-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide. The diastereoisomers were separated and purified by flash chromatography on silica gel (30 g and 40 g). Methanol/EE (1:1, ca. 600 ml) was used as eluent. The non-polar diastereoisomer of 4-(5-methoxy-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide [experiment 1 (116 mg, m.p. 106°-107° C., 32%) and experiment 2 (89 mg, m.p. 110°-112° C., 25%)], and the polar diastereoisomer of 4-(5-methoxy-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide [experiment 1 (108 mg, m.p. 98°-100° C., 30%) and experiment 2 (92 mg, m.p. 92°-97° C., 26%)] were thereby obtained in pure form.

Workup

  1. dissolutionwere dissolved in two microwave reaction vessels
  2. additionThe reaction mixture was treated with microwave radiation
  3. customexperiment 1 (150° C., 52 minutes) and experiment 2 (200° C., 2 minutes)
  4. distillationby distilling off the solvent in vacuo
  5. customThe diastereoisomers were separated
  6. custompurified by flash chromatography on silica gel (30 g and 40 g)

Sources & evidence

ORD record
ord-98cb8d9365a146c79d37551447cb7881
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

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