Potassium Carbonate → (R)-1-(3-chloropyrazin-2-yl)pyrrolidin-3-yl-[(R)-1-(naphthalen-1-yl)ethyl]amine

HRID 409575

Reaction equation

HRID 409575 reaction equation
Cl.Cl.[C:3]1([C@H:13]([NH:15][C@@H:16]2[CH2:20][CH2:19][NH:18][CH2:17]2)[CH3:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=1.[Cl:21][C:22]1[C:27](Cl)=[N:26][CH:25]=[CH:24][N:23]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)C>[Cl:21][C:22]1[C:27]([N:18]2[CH2:19][CH2:20][C@@H:16]([NH:15][C@@H:13]([C:3]3[C:12]4[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=4)[CH:6]=[CH:5][CH:4]=3)[CH3:14])[CH2:17]2)=[N:26][CH:25]=[CH:24][N:23]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 785752,3-DichloropyrazineHCID 67407230(R)-3-[(R)-1-(naphthalen-1-yl)ethylamino]pyrrolidine dihydrochloride

Product 1

HCID 58973557(R)-1-(3-chloropyrazin-2-yl)pyrrolidin-3-yl-[(R)-1-(naphthalen-1-yl)ethyl]amineYield 35.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 162 mg of (R)-3-[(R)-1-(naphthalen-1-yl)ethylamino]pyrrolidine dihydrochloride and 79.0 mg of 2,3-dichloro-pyrazine in 5 ml of ethanol was added 345 mg of potassium carbonate, and the mixture was stirred under reflux for 16 hours. The reaction mixture was filtered, and the solvent was evaporated, and to the residue was added a saturated aqueous sodium bicarbonate solution and chloroform, and the liquids were separated. The organic layer was dried, and the solvent was evaporated, then, the residue was purified by NH silica gel column chromatography (hexane:ethyl acetate-97:34→80:20) and by silica gel chromatography (hexane:ethyl acetate=90:10→0:100) to obtain 64.0 mg of (R)-1-(3-chloropyrazin-2-yl)pyrrolidin-3-yl-[(R)-1-(naphthalen-1-yl)ethyl]amine. (2) In 2 ml of chloroform was dissolved 64.0 mg of (R)-1-(3-chloropyrazin-2-yl)pyrrolidin-3-yl-[(R)-1-(naphthalen-1-yl)ethyl]amine, and 3 ml of a solution of 4M hydrochloric acid in dioxane was added to the mixture, and the resulting mixture was stirred. After the reaction mixture was concentrated under reduced pressure, diethyl ether was added to the residue, and the precipitates were collected by filtration, washed with diethyl ether, and dried to obtain 63.9 mg of (R)-1-(3-chloropyrazin-2-yl)pyrrolidin-3-yl-[(R)-1-(naphthalen-1-yl)ethyl]amine dihydrochloride (the following Table A2, Example 2.001).

Workup

  1. temperatureunder reflux for 16 hours
  2. filtrationThe reaction mixture was filtered
  3. customthe solvent was evaporated
  4. additionto the residue was added a saturated aqueous sodium bicarbonate solution and chloroform
  5. customthe liquids were separated
  6. customThe organic layer was dried
  7. customthe solvent was evaporated
  8. customthe residue was purified by NH silica gel column chromatography (hexane:ethyl acetate-97:34→80:20) and by silica gel chromatography (hexane:ethyl acetate=90:10→0:100)

Sources & evidence

ORD record
ord-9b3f8647c09544a78fe8d0647323925b
Source dataset
uspto-grants-2014_06
Patent number
US08759387B2

Linked notes

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