Water → HCID 86729390, compound

HRID 521225Notes

Reaction equation

HRID 521225 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([O-])=O.[C:8]([C:11]1[C:12]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[N:13][N:14]([C:16]2([CH2:20][C:21]#[N:22])[CH2:19][NH2+:18][CH2:17]2)[CH:15]=1)(=[O:10])[NH2:9].FC(F)(F)S(OCC(F)(F)F)(=O)=O.C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1>[C:21]([CH2:20][C:16]1([N:14]2[CH:15]=[C:11]([C:8]([NH2:9])=[O:10])[C:12]([NH:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[N:13]2)[CH2:17][N:18]([CH2:3][C:2]([F:7])([F:6])[F:1])[CH2:19]1)#[N:22]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 86729391HCID 86729391, compound

Product 1

HCID 86729390HCID 86729390, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a suspension of 3-[4-carbamoyl-3-(phenylamino)-1H-pyrazol-1-yl]-3-(cyanomethyl)azetidinium trifluoroacetate (Intermediate #38-2) (23 mg, 0.078 mmol) in dioxane (2 mL) was added 2,2,2-trifluoroethyl trifluoromethanesulfonate (36 mg, 0.15 mmol), followed by K2CO3 (23 mg, 0.078 mmol). The resulting mixture was heated to 110° C. and allowed to stir for 2 hours. The reaction was then cooled to ambient temperature, water was added and the reaction mixture was extracted with EtOAc (3×). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified by MPLC on silica gel (using a gradient elution of 0-100%, EtOAc/hexanes) to afford the title compound, Example #19. 1H NMR (600 MHz, CDCl3): δ 8.78 (s, 1H), 7.75 (s, 1H), 7.48 (d, J=7.7 Hz, 2H), 7.26 (t, J=7.9 Hz, 2H), 6.90 (t, J=7.3 Hz, 1H), 5.62 (s, 2H), 3.81 (d, J=8.6 Hz, 2H), 3.74 (d, J=8.6 Hz, 2H), 3.34 (s, 2H), 3.09 (q, J=9.1 Hz, 2H). LRMS (ESI) calc'd for C17H17F3N6O [M+H]+: 379. Found: 379.

Workup

  1. temperatureThe reaction was then cooled to ambient temperature
  2. extractionthe reaction mixture was extracted with EtOAc (3×)
  3. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by MPLC on silica gel (
  7. washa gradient elution of 0-100%, EtOAc/hexanes)

Sources & evidence

ORD record
ord-352069ff8fe64e63b81cc05173c82add
Source dataset
uspto-grants-2016_05
Patent number
US09328099B2

Reaction notes

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