2-Bromopyrimidine → (R)-1-(naphthalen-1-yl)ethyl-[(S)-1-(pyrimidin-2-yl)pyrrolidin-3-yl]amine

HRID 1811622Notes

Reaction equation

HRID 1811622 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.Br[C:22]1[N:27]=[CH:26][CH:25]=[CH:24][N:23]=1.C(N(C(C)C)CC)(C)C>O1CCOCC1>[C:3]1([C@H:13]([NH:15][C@H:16]2[CH2:20][CH2:19][N:18]([C:22]3[N:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[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

Participants

5

Reactant 3

HCID 783452-BromopyrimidineHCID 81531DiisopropylethylamineHCID 67408696(S)-3-[(R)-1-(naphthalen-1-yl)ethylamino]pyrrolidine dihydrochloride

Product 1

HCID 58973519(R)-1-(naphthalen-1-yl)ethyl-[(S)-1-(pyrimidin-2-yl)pyrrolidin-3-yl]amineYield 70.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a suspension of 156.6 mg of (S)-3-[(R)-1-(naphthalen-1-yl)ethylamino]pyrrolidine dihydrochloride in 5 ml of dioxane were added 87.4 mg of 2-bromopyrimidine and 207 mg of diisopropylethylamine, and the mixture was stirred under reflux for 16 hours. The reaction mixture was evaporated, and to the residue were added a saturated aqueous sodium bicarbonate solution and chloroform, the mixture was stirred and the liquids were separated. The organic layer was dried, the solvent was evaporated, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:2→0:1) to obtain 112 mg of (R)-1-(naphthalen-1-yl)ethyl-[(S)-1-(pyrimidin-2-yl)pyrrolidin-3-yl]amine. (2) In 10 ml of ethyl acetate was dissolved 112 mg of (R)-1-(naphthalen-1-yl)ethyl-[(S)-1-(pyrimidin-2-yl)pyrrolidin-3-yl]amine, and 1 ml of a solution of 4M hydrochloric acid in ethyl acetate was added to the mixture and the resulting mixture was stirred. The reaction mixture was concentrated under reduced pressure, to the residue was added diethyl ether, precipitates were collected by filtration and washed with ethyl acetate, to obtain 68.3 mg of (R)-1-(naphthalen-1-yl)ethyl-[(S)-1-(pyrimidin-2-yl)pyrrolidin-3-yl]amine dihydrochloride (the following Table A2, Example 2.010).

Workup

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

Sources & evidence

ORD record
ord-968e18be8a05418db63f2aaa6089daf3
Source dataset
uspto-grants-2013_01
Patent number
US08362274B2

Reaction notes

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