Hydrochloric Acid → N-Ethyl-1H-pyrrolo[2,3-b]pyridin-5-amine

HRID 1064261Notes

Reaction equation

HRID 1064261 reaction equation
C[N:2]([C:6]1[CH:7]=[C:8]2[CH:14]=[CH:13][N:12]([Si](C(C)C)(C(C)C)C(C)C)[C:9]2=[N:10][CH:11]=1)[C:3](=O)[CH3:4].Cl.[OH-].[Na+]>C1COCC1>[CH2:3]([NH:2][C:6]1[CH:7]=[C:8]2[CH:14]=[CH:13][NH:12][C:9]2=[N:10][CH:11]=1)[CH3:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 22273642HCID 22273642, compound

Product 1

HCID 22273641N-Ethyl-1H-pyrrolo[2,3-b]pyridin-5-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

Acetyl chloride (75 μL, 1.0 mmol) was added to a solution of 1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-5-ylamine (230 mg, 0.8 mmol) and 4-dimethylaminopyridine (5 mg) in pyridine (1.6 mL). The mixture was stirred at RT for 24 h and a saturated solution of ammonium chloride (30 mL) and ethyl acetate (30 mL) were added. The separated aqueous layer was extracted with ethyl acetate (3×25 mL) and the combined organic layers were dried, filtered and concentrated to provide an oil which was purified by preparative HPLC to afford N-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-acetamide (140 mg, 53%) as an oil: LCMS; m/z 332 (M+H+). B. At RT under argon, a solution of borane-dimethylsulfide complex (665 μL, 6.6 mmol, 10 M) was added to N-methyl-N-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-acetamide (110 mg, 0.33 mmol) in THF (3.0 mL). The mixture was heated to 65° C. for 2 h., cooled down and a 6N hydrochloric acid solution was slowly added. The mixture was heated to 100° C. and vigorously stirred for 12 h., cooled down and a 6 N sodium hydroxide solution was added until pH 7 was reached. The mixture was extracted with ethyl acetate (3×15 mL) and the combined organic layers were dried, filtered and evaporated to provide an oil which was purified through silica gel-SCX column (arylsulfonic acid with washes with methanol and 2N NH3 in methanol) to afford ethyl-(1H-pyrrolo[2,3-b]pyridin-5-yl)-amine. LCMS; m/z 203 (M+AcCN), 162 (M+H)+.

Workup

  1. temperaturecooled down
  2. temperatureThe mixture was heated to 100° C.
  3. temperaturecooled down
  4. extractionThe mixture was extracted with ethyl acetate (3×15 mL)
  5. customthe combined organic layers were dried
  6. filtrationfiltered
  7. customevaporated
  8. customto provide an oil which
  9. customwas purified through silica gel-SCX column (arylsulfonic acid with washes with methanol and 2N NH3 in methanol)

Sources & evidence

ORD record
ord-41755ce4e10044048c7961fae31fc689
Source dataset
uspto-grants-2005_11
Patent number
US06969717B2

Reaction notes

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