Hydrochloric Acid → 1H-Pyrrolo(2,3-b)pyridine

HRID 1490235Notes

Reaction equation

HRID 1490235 reaction equation
C(O[C:6]([NH:8][C:9]1[C:14]([CH3:15])=[CH:13][CH:12]=[CH:11][N:10]=1)=O)(C)(C)C.C([Li])CCC.CN(C)C=O.Cl>O1CCCC1>[NH:8]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:14]2[CH:15]=[CH:6]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 117458482-(N-Boc-Amino)-3-methylpyridineHCID 178418339Butyllithium

Product 1

HCID 92221H-Pyrrolo(2,3-b)pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of the product of step (a) (50.0 g) in tetrahydrofuran (1.0 liter) cooled to -5° C. was treated with n-butyllithium (210 ml, 0.53 mol, 2.5M, 2.2 eq) at such a rate as to maintain the temperature ≤+2° C. On complete addition (45 minutes) the resulting deep red mixture was aged at 0° C. for 1 hour. The vigorously stirred solution was then treated with anhydrous dimethylformamide (24.2 ml, 0.3 mol, 1.3 eq.) in one portion. The resulting yellow slurry was stirred at 10° C. to room temperature over 30 minutes and then treated, rapidly, with 5.5M hydrochloric acid (250 ml). The ensuing exotherm took the temperature to 45° C. The mixture was heated at 45° to 50° C. for 1 hour, cooled to room temperature and the phases separated. The organic phase was extracted with 2M hydrochloric acid (250 ml) and the combined aqueous phases cooled to 0° C. Isopropyl acetate (250 ml) was added and the stirred mixture treated with 5M sodium hydroxide solution (250 ml) at such a rate as to maintain the temperature at ≤20° C. The mixture was stirred for 5 minutes, allowed to settle and the phases separated. The aqueous phase was extracted with isopropyl acetate (250 ml). The combined isopropyl acetate phases were washed with saturated brine (250 ml) and the isopropyl acetate solution assayed for 7-azaindole: HPLC assay=94.7%w/w (method 2) yield=26.8 g.

Workup

  1. temperatureto maintain the temperature ≤+2° C
  2. additionOn complete addition (45 minutes) the resulting deep red mixture
  3. additiontreated
  4. customto 45° C
  5. temperatureThe mixture was heated at 45° to 50° C. for 1 hour
  6. customthe phases separated
  7. extractionThe organic phase was extracted with 2M hydrochloric acid (250 ml)
  8. temperaturethe combined aqueous phases cooled to 0° C
  9. additionIsopropyl acetate (250 ml) was added
  10. additionthe stirred mixture treated with 5M sodium hydroxide solution (250 ml) at such a rate as
  11. temperatureto maintain the temperature at ≤20° C
  12. stirringThe mixture was stirred for 5 minutes
  13. customthe phases separated
  14. extractionThe aqueous phase was extracted with isopropyl acetate (250 ml)
  15. washThe combined isopropyl acetate phases were washed with saturated brine (250 ml)

Sources & evidence

ORD record
ord-253f09749b8145358c8b814f2940cd47
Source dataset
uspto-grants-1997_10
Patent number
US05681959

Reaction notes

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