Sodium Bicarbonate → 3-Amino-7-fluoro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester

HRID 2264935Notes

Reaction equation

HRID 2264935 reaction equation
Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[CH:4][C:3]=1[F:10].Cl.[CH2:12]([O:14][C:15](=[O:18])[CH2:16][NH2:17])[CH3:13].C(=O)([O-])O.[Na+]>>[CH2:12]([O:14][C:15]([C:16]1[NH:17][C:2]2[C:3]([F:10])=[CH:4][N:5]=[CH:6][C:7]=2[C:8]=1[NH2:9])=[O:18])[CH3:13]

Participants

4

Reactant 3

HCID 516892Sodium BicarbonateHCID 2723640Glycine ethyl ester, hydrochlorideHCID 595964283-Pyridinecarbonitrile, 4-chloro-5-fluoro-

Product 1

HCID 595966093-Amino-7-fluoro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl esterYield 46%

Procedure

A mixture of 4-chloro-5-fluoro-nicotinonitrile (3.5 g, 22.4 mmol), glycine ethyl ester hydrochloride (9.4 g, 67.1 mmol) and sodium hydrogencarbonate (11.3 g, 134.2 mmol) in IMS (60 mL) was stirred at reflux for 18 hours. The reaction was then cooled to room temperature and partitioned between water and ethyl acetate. The organic layer was separated and washed with water and brine, dried over sodium sulphate, filtered and concentrated to give a solid which was triturated in diethyl ether. The mixture was aged at room temperature for 18 hours and the precipitate was filtered off and dried under vacuum at 60° C. to give the title compound as a beige solid (2.29 g, 46%). LCMS (method B): RT=1.50 min, M+H+=224.

Workup

  1. temperatureat reflux for 18 hours
  2. custompartitioned between water and ethyl acetate
  3. customThe organic layer was separated
  4. washwashed with water and brine
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a solid which
  9. customwas triturated in diethyl ether
  10. filtrationthe precipitate was filtered off
  11. customdried under vacuum at 60° C.

Sources & evidence

ORD record
ord-fd5d3ec7d9b643518b886864bbe0a736
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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