Potassium Fluoride → HCID 118093615, compound

HRID 1520102Notes

Reaction equation

HRID 1520102 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]([N:23]([CH3:31])C(=O)OC(C)(C)C)(=[O:22])=[O:21])=[CH:15][CH:14]=2)[CH:6]=1.Cl[C:33]1[N:38]=[CH:37][C:36]([Cl:39])=[CH:35][N:34]=1>CS(C)=O>[Cl:39][C:36]1[CH:35]=[N:34][C:33]([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][CH3:31])(=[O:21])=[O:22])=[CH:17][CH:18]=3)[CH:6]=2)=[N:38][CH:37]=1

Participants

5

Reactant 3

HCID 522689Potassium FluorideHCID 5906412,5-DichloropyrimidineHCID 118093616HCID 118093616, compound

Product 1

HCID 118093615HCID 118093615, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

Add potassium fluoride (53.9 mg, 0.93 mmol) to a solution of tert-butyl N-[[4-[6-(aminomethyl)-2-methyl-pyrimidin-4-yl]oxyphenyl]methylsulfonyl]-N-methyl-carbamate (280 mg, 0.46 mmol) and 2,5-dichloropyrimidine (69.1 mg, 0.46 mmol) in DMSO (10 mL). Heat the mixture to 120° C. and stir it at that temperature for 17 hours. Cool the mixture to ambient temperature and quench the reaction with water. Extract the resulting mixture with EtOAc; combine the extract(s); dry the extracts with magnesium sulfate; filter; and concentrate the filtrate under reduce pressure to provide a residue. Purify the title compound using silica gel chromatography eluting with a gradient of EtOAc in hexanes (0-100%). Further purify the title compound using a second silica gel chromatography eluting with a gradient of 0-10% MeOH in DCM. Concentrate the appropriate fractions under reduced pressure to provide the title compound as a glassy yellow solid (90 mg, 44.6%). MS (m/z): 435 (M+1).

Workup

  1. temperatureCool the mixture to ambient temperature
  2. customquench
  3. customthe reaction with water
  4. extractionExtract the resulting mixture with EtOAc
  5. extractionextract(s)
  6. dry with materialdry the extracts with magnesium sulfate
  7. filtrationfilter
  8. concentrationand concentrate the filtrate
  9. customto provide a residue
  10. customPurify the title compound
  11. washeluting with a gradient of EtOAc in hexanes (0-100%)
  12. customFurther purify the title compound
  13. washeluting with a gradient of 0-10% MeOH in DCM
  14. concentrationConcentrate the appropriate fractions under reduced pressure

Sources & evidence

ORD record
ord-7384a8e39b9f46fea4a70b4ca2456f6e
Source dataset
uspto-grants-2015_07
Patent number
US09073901B2

Reaction notes

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