Ethanol → HCID 86679611, compound

HRID 577665Notes

Reaction equation

HRID 577665 reaction equation
[F:1][C:2]1[C:10]2[C:9]([O:11][C:12]3[CH:13]=[C:14]([NH:18][C:19](=[O:22])[CH:20]=[CH2:21])[CH:15]=[CH:16][CH:17]=3)=[N:8][C:7]([NH:23][C:24]3[CH:28]=[CH:27][N:26]([CH3:29])[N:25]=3)=[N:6][C:5]=2[N:4](COCC[Si](C)(C)C)[CH:3]=1.C(O)(C(F)(F)F)=O.CCO.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.O>[F:1][C:2]1[C:10]2[C:9]([O:11][C:12]3[CH:13]=[C:14]([NH:18][C:19](=[O:22])[CH:20]=[CH2:21])[CH:15]=[CH:16][CH:17]=3)=[N:8][C:7]([NH:23][C:24]3[CH:28]=[CH:27][N:26]([CH3:29])[N:25]=3)=[N:6][C:5]=2[NH:4][CH:3]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 86679609HCID 86679609, compound

Product 1

HCID 86679611HCID 86679611, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution N-{3-[(5-fluoro-2-[(1-methyl-1H-pyrazol-3-yl)amino]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy]phenyl}prop-2-enamide (120 mg, 0.23 mmol) in DCM (10 mL) was added TFA (0.7 mL, 6.7 mmol). The reaction solution was stirred at rt for 4 hrs. The reaction was evaporated to dryness and EtOH (5 mL), water (1 mL), and K2CO3 (158 mg, 1.1 mmol) were added. The reaction mixture was stirred at rt for 2 hrs and concentrated to dryness, suspended in EtOAc and filtered. The filtrate was concentrated to dryness and then suspended in EtOAc (20 mL) and heated to 70° C. with stirring for 30 min. The mixture was then cooled to rt with stirring overnight. A light yellow solid precipitated over this time and was collected by filtration, washed with EtOAc (5 mL) and dried to afford the title compound (50.2 mg, 56% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.25 (br. s., 1H) 10.27 (s, 1H) 9.25 (s, 1H) 7.64 (s, 1H) 7.53-7.60 (m, 1H) 7.41 (t, J=8.06 Hz, 1H) 7.28 (d, J=1.26 Hz, 1H) 7.02 (dd, J=7.93, 1.89 Hz, 1H) 6.99 (s, 1H) 6.38-6.48 (m, 1H) 6.05 (br. s., 1H) 5.77 (dd, J=10.07, 1.51 Hz, 1H) 3.65 (s, 4H). m/z (APCI+) for C19H16FN7O2 394.1 (M+H)+.

Workup

  1. additionwere added
  2. stirringThe reaction mixture was stirred at rt for 2 hrs
  3. concentrationconcentrated to dryness
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated to dryness
  6. temperatureheated to 70° C.
  7. stirringwith stirring for 30 min
  8. temperatureThe mixture was then cooled to rt
  9. stirringwith stirring overnight
  10. customA light yellow solid precipitated over this time
  11. filtrationwas collected by filtration
  12. washwashed with EtOAc (5 mL)
  13. customdried

Sources & evidence

ORD record
ord-c13ba12d938748209ff2c114df7e3be0
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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