Hydrochloric Acid → HCID 58382020, compound

HRID 1628112Notes

Reaction equation

HRID 1628112 reaction equation
[CH2:1]([C:3]1[C:11]2[C:6](=[N:7][CH:8]=[C:9]([NH:12]C(=O)OC(C)(C)C)[N:10]=2)[N:5]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:4]=1[C:28]1[CH:33]=[CH:32][C:31]([C:34]2([CH3:39])OCC[O:35]2)=[CH:30][CH:29]=1)[CH3:2].C(O)(C(F)(F)F)=O.Cl.C([O-])(O)=O.[Na+]>O1CCOCC1.O.CCOC(C)=O>[NH2:12][C:9]1[N:10]=[C:11]2[C:3]([CH2:1][CH3:2])=[C:4]([C:28]3[CH:29]=[CH:30][C:31]([C:34](=[O:35])[CH3:39])=[CH:32][CH:33]=3)[N:5]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:25])[CH3:26])[C:6]2=[N:7][CH:8]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acid2×HCID 516892Sodium BicarbonateHCID 67362308HCID 67362308, compound

Product 1

HCID 58382020HCID 58382020, compoundYield 84%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

tert-Butyl 7-ethyl-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylcarbamate (0.35 g, 0.631 mmol) in 1,4-dioxane (5 mL) was treated with TFA (0.073 mL, 0.946 mmol) then the solution was stirred for about 15 min at rt. The mixture was heated to about 60° C. for about 15 min and then TFA (0.145 mL, 1.88 mmol) was added and heating continued at about 75° C. for about 1 h. The solution was cooled to rt then concentrated (37%) aqueous HCl (0.083 mL, 1.015 mmol) was added. The mixture was stirred for about 15 min at rt then warmed to about 75° C. for about 4 h. The mixture was cooled then treated with saturated aqueous NaHCO3 (10 mL), EtOAc (25 mL) and water (10 mL). The layers were separated then the aqueous layer extracted with EtOAc (15 mL). The organics were combined then dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The material was purified on a 10 g silica gel column with EtOAc as an eluent to give 1-(4-(2-amino-7-ethyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-6-yl)phenyl)ethanone (0.217 g, 84%): LC/MS (Table 2, Method a) Rt=2.72 min; MS m/z 411 (M+H)+.

Workup

  1. temperatureThe mixture was heated to about 60° C. for about 15 min
  2. temperatureheating
  3. waitcontinued at about 75° C. for about 1 h
  4. temperatureThe solution was cooled to rt
  5. additionwas added
  6. stirringThe mixture was stirred for about 15 min at rt
  7. temperaturethen warmed to about 75° C. for about 4 h
  8. temperatureThe mixture was cooled
  9. customThe layers were separated
  10. extractionthe aqueous layer extracted with EtOAc (15 mL)
  11. dry with materialThe organics were combined then dried over anhydrous MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customThe material was purified on a 10 g silica gel column with EtOAc as an eluent

Sources & evidence

ORD record
ord-050728bc147845d2830fb9426445993f
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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