Potassium Carbonate → 1-Methyl-cyclohexanecarboxylic acid {(1R)-2-[4-(1H-indol-4-yl)piperazin-1-yl]-1-pyridin-2-ylmethyl-ethyl}-methyl-amide

HRID 1830609Notes

Reaction equation

HRID 1830609 reaction equation
[NH:1]1[C:9]2[C:4](=[C:5]([N:10]3[CH2:15][CH2:14][N:13]([CH2:16][C@H:17]([NH:25][CH3:26])[CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)[CH2:12][CH2:11]3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.C(=O)([O-])[O-].[K+].[K+].[CH3:33][C:34]1([C:40](Cl)=[O:41])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1>ClCCl.O>[NH:1]1[C:9]2[C:4](=[C:5]([N:10]3[CH2:15][CH2:14][N:13]([CH2:16][C@H:17]([N:25]([CH3:26])[C:40]([C:34]4([CH3:33])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]4)=[O:41])[CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)[CH2:12][CH2:11]3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 41892451-Methylcyclohexanecarbonyl chlorideHCID 58651200(2R)-1-[4-(1H-indol-4-yl)piperazin-1-yl]-N-methyl-3-pyridin-2-yl propan-2-amine

Product 1

HCID 112828781-Methyl-cyclohexanecarboxylic acid {(1R)-2-[4-(1H-indol-4-yl)piperazin-1-yl]-1-pyridin-2-ylmethyl-ethyl}-methyl-amide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a solution of (2R)-1-[4-(1H-indol-4-yl)piperazin-1-yl]-N-methyl-3-pyridin-2-ylpropan-2-amine (349 mg.; 1 mmol, from Example 20) in dichloromethane (10 mL) at 0° C. is added a solution of potassium carbonate (690 mg.; 5 mmol) in water (1.6 mL), followed by a solution of 1-methyl-1-cyclohexanecarbonyl chloride (160 mg.; 1 mmol) in dichloromethane (1.6 mL). The reaction mixture is stirred while allowing to warm to ambient temperature over 1 hour, diluted with dichloromethane (20 mL), and the layers allowed to separate. The organic layer is dried over MgSO4, filtered, and the solvent removed in vacuo. The crude residue is purified by flash chromatography on silica gel (10% methanol/ethyl acetate) to yield the free base of the title compound. The fumarate salt is prepared by treatment with an equimolar amount of fumaric acid in ethanol.

Workup

  1. customto separate
  2. dry with materialThe organic layer is dried over MgSO4
  3. filtrationfiltered
  4. customthe solvent removed in vacuo
  5. customThe crude residue is purified by flash chromatography on silica gel (10% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-fa176ff639d24d5e8ab68a59d0c6cbbf
Source dataset
uspto-grants-2006_06
Patent number
US07067518B2

Reaction notes

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