Trifluoroacetic acid → HCID 66990883, compound

HRID 2367239Notes

Reaction equation

HRID 2367239 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[N:16]=[C:15]([NH:17]CC4C=CC(OC)=CC=4OC)[N:14]=[C:13]([N:29]4[C@H:34]([C:35]([F:38])([F:37])[F:36])[CH2:33][CH2:32][C@H:31]([C:39]([NH:41][CH:42]5[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]5)=[O:40])[CH2:30]4)[CH:12]=3)=[CH:8][CH:9]=2)[NH:4][N:3]=1.FC(F)(F)C(O)=O.CCCCCC>CCOC(C)=O>[NH2:17][C:15]1[N:14]=[C:13]([N:29]2[C@H:34]([C:35]([F:37])([F:36])[F:38])[CH2:33][CH2:32][C@H:31]([C:39]([NH:41][CH:42]3[CH2:43][CH2:44][CH2:45][CH2:46][CH2:47]3)=[O:40])[CH2:30]2)[CH:12]=[C:11]([C:7]2[CH:6]=[C:5]3[C:10]([C:2]([NH2:1])=[N:3][NH:4]3)=[CH:9][CH:8]=2)[N:16]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 8058HexaneHCID 66990952HCID 66990952, compound

Product 1

HCID 66990883HCID 66990883, compoundYield 18.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To cis-1-[6-(3-amino-1H-indazol-6-yl)-2-({[2,4-bis(methyloxy)phenyl]methyl}amino)-4-pyrimidinyl]-N-cyclohexyl-6-(trifluoromethyl)-3-piperidinecarboxamide (250 mg, 0.38 mmol) was added trifluoroacetic acid (TFA) (6 mL). After 3 hours, LCMS analysis indicated the reaction to be completed. The reaction mixture was concentrated under vacuum, and the resulting residue was co-evaporated from toluene (2×50 mL), then from CH3CN (50 mL). To the resulting pink solid was added a saturated aqueous NaHCO3 solution and EtOAc. The organic layer was separated, and the aqueous layer was further extracted with EtOAc. The combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated. This material was purified by flash chromatography (gradient: 100% CH2Cl2 to 90:10:1 CH2Cl2:CH3OH:NH4OH). The cleaner fractions were combined and concentrated under vacuum to afford a yellow solid. This material was dissolved in EtOAc (˜2 mL), and the resulting solution was transfered to a microwave vial. The vial was capped, and heated to 70 C. Hexane was added dropwise until the solution became cloudy, then the mixture was allowed to cool to room temperature. A spatula was used to scrap the solid, and the mixture was filtered. The collected pink solid was washed with hexanes and a white solid precipitate from the filtrate. This white solid was collected by filtration to afford the desired product (35 mg). LC-MS (ES) m/z=503 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.05-1.34 (m, 5H), 1.56 (m, 1H), 1.63-1.85 (m, 7H), 2.07 (m, 1H), 2.33, (m, 1H), 3.06 (bs, 1H), 3.53 (m, 1H), 5.39 (s, 2H), 6.29 (s, 2H), 6.78 (s, 1H), 7.63 (dd, J=8.5, 1.1 Hz, 1H), 7.72 (d, J=8.4 Hz, 1H), 7.84 (d, J=7.9 Hz, 1H), 7.99 (s, 1H), 11.54 (s, 1H).

Workup

  1. customthe reaction
  2. concentrationThe reaction mixture was concentrated under vacuum
  3. additionTo the resulting pink solid was added a saturated aqueous NaHCO3 solution and EtOAc
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was further extracted with EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThis material was purified by flash chromatography (gradient: 100% CH2Cl2 to 90:10:1 CH2Cl2:CH3OH:NH4OH)
  11. concentrationconcentrated under vacuum
  12. customto afford a yellow solid
  13. customThe vial was capped
  14. temperatureheated to 70 C
  15. filtrationthe mixture was filtered
  16. washThe collected pink solid was washed with hexanes
  17. filtrationThis white solid was collected by filtration

Sources & evidence

ORD record
ord-88fc7ef50dfb4c09b4837b7eeb51b838
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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