Hydrochloric Acid → 3-fluoro-4-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yloxy)-phenylamine

HRID 1851094Notes

Reaction equation

HRID 1851094 reaction equation
C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[CH:20]=[CH:19][N:18]=[C:17]3[N:21](COCC[Si](C)(C)C)[C:22]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:23][C:16]=23)=[C:10]([F:38])[CH:9]=1)(C)(C)C.Cl>CO>[F:38][C:10]1[CH:9]=[C:8]([NH2:7])[CH:13]=[CH:12][C:11]=1[O:14][C:15]1[CH:20]=[CH:19][N:18]=[C:17]2[NH:21][C:22]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:23][C:16]=12

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 583683903-fluoro-4-[2-phenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-4-yloxy]-phenyl-carbamic acid t-butyl ester

Product 1

HCID 583683593-fluoro-4-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yloxy)-phenylamineYield 40%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a solution of 3-fluoro-4-[2-phenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-4-yloxy]-phenyl-carbamic acid t-butyl ester in methanol, a 1:1 solution (10 mL) of hydrochloric acid and methanol was added. The mixture was stirred at room temperature for 4 hours. The resulting reaction mixture was concentrated under reduced pressure and ether was added to the resulting residue. After stirring for 2 hours, the produced solid was collected by filtering. Thus obtained hydrochloride was dissolved in water and neutralized to about pH 8 by adding 1 M sodium hydroxide aqueous solution. The resulting mixture was extracted with ethyl acetate. The organic layer was separated and washed with sodium chloride aqueous solution. The organic layer was dried with Na2SO4 and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=1:1) to give the target compound as a white solid (81 mg, 0.25 mmol, 40% yield).

Workup

  1. customThe resulting reaction mixture
  2. concentrationwas concentrated under reduced pressure and ether
  3. additionwas added to the resulting residue
  4. stirringAfter stirring for 2 hours
  5. customthe produced solid was collected
  6. filtrationby filtering
  7. dissolutionThus obtained hydrochloride was dissolved in water and neutralized to about pH 8
  8. additionby adding 1 M sodium hydroxide aqueous solution
  9. extractionThe resulting mixture was extracted with ethyl acetate
  10. customThe organic layer was separated
  11. washwashed with sodium chloride aqueous solution
  12. dry with materialThe organic layer was dried with Na2SO4
  13. filtrationfiltered
  14. concentrationThe filtrate was concentrated under reduced pressure
  15. customThe resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-e5dbc61b7312445b85c8a27c4bc90c77
Source dataset
uspto-grants-2015_02
Patent number
US08957102B2

Reaction notes

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