Hydrochloric Acid → Ethyl 6-amino-1H-pyrrolo[2,3-B]pyridine-5-carboxylate

HRID 2080008Notes

Reaction equation

HRID 2080008 reaction equation
[B]1OC2[C:3](=[CH:4]C=CC=2)O1.C(OC#C)C.[CH2:15]([O:17][C:18](=[O:28])[C:19]1[CH:24]=[C:23](I)[C:22]([NH2:26])=[N:21][C:20]=1[NH2:27])[CH3:16].[OH-].[Na+].Cl>O1CCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:15]([O:17][C:18]([C:19]1[CH:24]=[C:23]2[CH:4]=[CH:3][NH:26][C:22]2=[N:21][C:20]=1[NH2:27])=[O:28])[CH3:16]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 61239Ether, ethyl ethynylHCID 6327445BenzcatechinboraneHCID 583880482,6-Diamino-5-iodo-nicotinic acid ethyl ester

Product 1

HCID 58387889Ethyl 6-amino-1H-pyrrolo[2,3-B]pyridine-5-carboxylateYield 35%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Catechol borane (2.7 mL, 1M tetrahydrofuran solution, 2.7 mmol) was added dropwise to ethoxyacetylene (0.7 mL, 40% hexane solution, 2.83 mmol) on an ice bath, and the mixture was stirred for 1 hour at room temperature. The mixture was further heated at 70° C. and stirred for 2 hours, and allowed to room temperature. A solution of 2,6-diamino-5-iodo-nicotinic acid ethyl ester described in Preparation Example R-1 (415 mg, 1.35 mmol) in tetrahydrofuran (5.5 mL), tetrakis(triphenylphosphine)palladium(0) (48 mg, 0.042 mmol) and sodium hydroxide (160 mg, 4 mmol, powder) were added thereto, followed by stirring for 7 hours 30 minutes under reflux. The reaction mixture was allowed to room temperature, 2N hydrochloric acid (4.7 mL, 9.4 mmol) was added thereto, followed by stirring for 60 hours at room temperature. After the reaction was completed, the reaction mixture was evaporated, and extracted using diethyl ether. The aqueous layer was fractionated, neutralized on an ice bath with an aqueous solution of 5N sodium hydroxide, then, was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, then evaporated, the resulting residue was purified by silica gel column chromatography (ethyl acetate:hexane=2:1), and the title compound (97 mg, 0.47 mmol, 35%) was obtained.

Workup

  1. temperatureThe mixture was further heated at 70° C.
  2. stirringstirred for 2 hours
  3. customallowed to room temperature
  4. stirringby stirring for 7 hours 30 minutes
  5. temperatureunder reflux
  6. customwas allowed to room temperature
  7. stirringby stirring for 60 hours at room temperature
  8. customthe reaction mixture was evaporated
  9. extractionextracted
  10. customneutralized on an ice bath with an aqueous solution of 5N sodium hydroxide
  11. extractionwas extracted with ethyl acetate
  12. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  13. customevaporated
  14. customthe resulting residue was purified by silica gel column chromatography (ethyl acetate:hexane=2:1)

Sources & evidence

ORD record
ord-864cb82009ad449aaca50b352d6a5600
Source dataset
uspto-grants-2011_04
Patent number
US07932272B2

Reaction notes

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