Potassium Fluoride → HCID 118093615, compound

HRID 1520099Notes

Reaction equation

HRID 1520099 reaction equation
[F-].[K+].[NH2:3][CH2:4][C:5]1[N:10]=[C:9]([CH3:11])[N:8]=[C:7]([O:12][C:13]2[CH:18]=[CH:17][C:16]([CH2:19][S:20]([NH:23][CH3:24])(=[O:22])=[O:21])=[CH:15][CH:14]=2)[CH:6]=1.Cl[C:26]1[N:31]=[CH:30][C:29]([Cl:32])=[CH:28][N:27]=1>CS(C)=O>[Cl:32][C:29]1[CH:28]=[N:27][C:26]([NH:3][CH2:4][C:5]2[N:10]=[C:9]([CH3:11])[N:8]=[C:7]([O:12][C:13]3[CH:14]=[CH:15][C:16]([CH2:19][S:20]([NH:23][CH3:24])(=[O:22])=[O:21])=[CH:17][CH:18]=3)[CH:6]=2)=[N:31][CH:30]=1

Participants

5

Reactant 3

HCID 522689Potassium FluorideHCID 5906412,5-DichloropyrimidineHCID 118093612HCID 118093612, compound

Product 1

HCID 118093615HCID 118093615, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

Add potassium fluoride (1.82 g, 31.33 mmol) to a solution of 1-[4-[6-(aminomethyl)-2-methyl-pyrimidin-4-yl]oxyphenyl]-N-methyl-methanesulfonamide (11.1 g, 24.10 mmol) and 2,5-dichloropyrimidine (4.31 g, 28.92 mmol) in DMSO (111 mL). Heat the reaction mixture at 120° C. for two hours. Thereafter cool the mixture to room temperature; add water (200 mL), and extract with EtOAc (3×200 mL). Combine the organic extracts; sequentially wash the organic extracts with water (300 mL) then brine (300 mL); dry over sodium sulfate; filter; and concentrate the filtrate under reduced pressure to provide title compound as a crude material. Purify the title compound using silica gel chromatography eluting with a gradient of hexane/EtOAc (1:1) to EtOAc (100%). Collect the relevant fractions containing the title compound and concentrate the fractions. Dissolve the resulting material in THF (200 mL) and EtOAc (300 mL), then add SiliaMetS® Thiol (9.2 g) to remove traces of palladium. Stir the mixture for 2 hr at 55° C. Filter the mixture at 55° C.; collect the filtrate; and evaporate the solvent to provide a solid. Triturate the solid with cold EtOAc (20 mL); collect the solid by filtration; and dry the solid under reduced pressure to provide the title compound as a white solid (8 g, 75%). MS (m/z): 435 (M+1).

Workup

  1. temperatureThereafter cool the mixture to room temperature
  2. extractionadd water (200 mL), and extract with EtOAc (3×200 mL)
  3. washsequentially wash the organic extracts with water (300 mL)
  4. dry with materialdry over sodium sulfate
  5. filtrationfilter
  6. concentrationand concentrate the filtrate under reduced pressure

Sources & evidence

ORD record
ord-1ceabf4145c64b188028d18a9e0d660f
Source dataset
uspto-grants-2015_07
Patent number
US09073901B2

Reaction notes

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