2,2,2-Trifluoroethyl trifluoromethanesulfonate → HCID 67456733, compound

HRID 1853055Notes

Reaction equation

HRID 1853055 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3](O)=O.[CH3:8][N:9]1[CH:13]=[C:12]([C:14]2[N:19]=[C:18]([C:20]3[CH:24]=[CH:23][N:22]([C:25]4([CH2:29][C:30]#[N:31])[CH2:28][NH:27][CH2:26]4)[CH:21]=3)[N:17]3[CH:32]=[CH:33][N:34]=[C:16]3[CH:15]=2)[CH:11]=[N:10]1.CCN(C(C)C)C(C)C.FC(F)(F)S(OCC(F)(F)F)(=O)=O>CN(C=O)C.C(Cl)Cl>[CH3:8][N:9]1[CH:13]=[C:12]([C:14]2[N:19]=[C:18]([C:20]3[CH:24]=[CH:23][N:22]([C:25]4([CH2:29][C:30]#[N:31])[CH2:28][N:27]([CH2:3][C:2]([F:7])([F:6])[F:1])[CH2:26]4)[CH:21]=3)[N:17]3[CH:32]=[CH:33][N:34]=[C:16]3[CH:15]=2)[CH:11]=[N:10]1

Participants

6

Reactant 3

HCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 81531DiisopropylethylamineHCID 67458185HCID 67458185, compound

Product 1

HCID 67456733HCID 67456733, compoundYield 31.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 2-(3-(3-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrrol-1-yl)azetidin-3-yl)acetonitrile trifluoroacetate (Example 127, 100 mg, 0.182 mmol) in dry DMF (1.0 mL) was cooled on an ice bath and DIEA (191 μL, 1.09 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (63.5 mg, 0.273 mmol) were added sequentially. The ice bath was removed and the reaction mixture was stirred at ambient temperature for 17 hours. The mixture was added to H2O (5 mL), mixed and extracted with DCM. The combined organic extracts were washed with 0.5M Na2CO3 and H2O, and dried over Na2SO4. The crude material was eluted through a SiO2 plug eluting first with DCM then 10% MeOH/EtOAc. The 10% MeOH/EtOAc pool was concentrated to give a colorless glass. The glass was dissolved in minimal DCM and treated with hexanes to afford a white suspension. The suspension was concentrated providing the title compound (25 mg, 31% yield) as a white solid. MS (apci) m/z=441.2.

Workup

  1. customThe ice bath was removed
  2. additionThe mixture was added to H2O (5 mL)
  3. additionmixed
  4. extractionextracted with DCM
  5. washThe combined organic extracts were washed with 0.5M Na2CO3 and H2O
  6. dry with materialdried over Na2SO4
  7. washThe crude material was eluted through a SiO2 plug
  8. washeluting first with DCM
  9. concentrationThe 10% MeOH/EtOAc pool was concentrated
  10. customto give a colorless glass
  11. customto afford a white suspension
  12. concentrationThe suspension was concentrated

Sources & evidence

ORD record
ord-e9ce75500df34205aeafd754ab201028
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

Loading…