Dimethylformamide → HCID 178506185, compound

HRID 661401Notes

Reaction equation

HRID 661401 reaction equation
[F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[C:5]([NH:9][C:10]2[NH:11][C:12]([C:15]3[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=3)=[N:13][N:14]=2)[CH:6]=[CH:7][CH:8]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[C:31]1[CH:32]=[N:33][CH:34]=[N:35][CH:36]=1.CN(C=O)C>O1CCOCC1.CO>[N:33]1[CH:32]=[C:31]([O:21][C:18]2[CH:19]=[CH:20][C:15]([C:12]3[NH:11][C:10]([NH:9][C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:22])([F:1])[F:23])[CH:4]=4)=[N:14][N:13]=3)=[CH:16][CH:17]=2)[CH:36]=[N:35][CH:34]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 783445-BromopyrimidineHCID 178515914HCID 178515914, compound

Product 1

HCID 178506185HCID 178506185, compoundYield 28.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

4-(5-{[3-(trifluoromethyl)phenyl]amino}-4H-1,2,4-triazol-3-yl)phenol (100 mg, 0.31 mmol) was dissolved in 3 mL of anhydrous dioxane in 2-5 mL microwave vial (Personal Chemistry). Solid Cs2CO3 (203.4 mg, 0.62 mmol) was added, followed by 5-bromo-pyrimidine (100 mg, 0.62 mmol). Then 1 mL of anhydrous DMF was added, the vial was capped and microwaved at 250° C. for 30 min. Then ca. 3 mL of MeOH was added to dissolve the formed suspension, the solution was transferred into a round-bottom flask and solvent was removed in vacuo. The residue was re-dissolved in 3 mL of DMF, filtered through 0.22 u syringe filter and purified by reverse phase preparative HPLC using acetonitrile/water system with 0.01% of TFA. The fractions containing the product were collected and partitioned between EtOAc and saturated aqueous NaHCO3. Ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate and filtered. Solvent was removed in vacuo to give the title compound as a light-brown foamy solid (34.7 mg).

Workup

  1. customthe vial was capped
  2. custommicrowaved at 250° C. for 30 min
  3. dissolutionto dissolve the formed suspension
  4. customthe solution was transferred into a round-bottom flask
  5. customsolvent was removed in vacuo
  6. dissolutionThe residue was re-dissolved in 3 mL of DMF
  7. filtrationfiltered through 0.22 u syringe
  8. filtrationfilter
  9. custompurified by reverse phase preparative HPLC
  10. additionThe fractions containing the product
  11. customwere collected
  12. custompartitioned between EtOAc and saturated aqueous NaHCO3
  13. washEthyl acetate layer was washed with brine
  14. dry with materialdried over anhydrous sodium sulfate
  15. filtrationfiltered
  16. customSolvent was removed in vacuo

Sources & evidence

ORD record
ord-ac752d4075194b03ac0bf237b7e9d9ec
Source dataset
uspto-grants-2011_12
Patent number
US08084618B2

Reaction notes

Loading…