Dimethylamine → 1-(6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-2-chloropyrimidin-4-yl)-N,N-dimethylmethanamine

HRID 75458Notes

Reaction equation

HRID 75458 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH:13]3[CH2:14][CH2:15][CH:9]2[CH2:10][O:11][CH2:12]3)[CH:5]=[C:4]([CH2:16]Cl)[N:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:24][NH:25][CH3:26]>CN(C=O)C>[CH:13]12[N:8]([C:6]3[N:7]=[C:2]([Cl:1])[N:3]=[C:4]([CH2:16][N:25]([CH3:26])[CH3:24])[CH:5]=3)[CH:9]([CH2:15][CH2:14]1)[CH2:10][O:11][CH2:12]2

Participants

5

Reactant 3

HCID 674DimethylamineHCID 11430Potassium CarbonateHCID 866659078-(2-Chloro-6-(chloromethyl)pyrimidin-4-yl)-3-oxa-8-azabicyclo[3.2.1]octane

Product 1

HCID 866659081-(6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-2-chloropyrimidin-4-yl)-N,N-dimethylmethanamineYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A flask was charged with 8-(2-chloro-6-(chloromethyl)pyrimidin-4-yl)-3-oxa-8-azabicyclo[3.2.1]octane (2.30 g, 8.39 mmol) and DMF (40 ml) was added to give a yellow solution. Potassium carbonate (2.90 g, 20.97 mmol) and dimethylamine (2.0M in THF, 4.6 ml, 9.23 mmol) were added and the reaction was allowed to stir at room temperature for 16 hours. The reaction mixture was filtered through a Buchner funnel and washed with methylene chloride and ethyl acetate. The filtrate was concentrated to provide crude product as a brown oil, which solidified upon standing (2.61 g). The crude product was added to a silica gel column and was eluted with 0-10% methanol in methylene chloride to provide 1-(6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-2-chloropyrimidin-4-yl)-N,N-dimethylmethanamine (2.01 g, 85%) as an off-white solid. HRMS; [M+H]+ Obs'd=283.1320, [M+H]+ Calc'd=283.1319.

Workup

  1. additionwas added
  2. customto give a yellow solution
  3. filtrationThe reaction mixture was filtered through a Buchner funnel
  4. washwashed with methylene chloride and ethyl acetate
  5. concentrationThe filtrate was concentrated
  6. customto provide crude product as a brown oil, which
  7. washwas eluted with 0-10% methanol in methylene chloride

Sources & evidence

ORD record
ord-f2bcaf69764f424fbca75e5e95a553cc
Source dataset
uspto-grants-2014_09
Patent number
US08835429B2

Reaction notes

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