Acetic Acid → HCID 178524701, compound

HRID 1611480Notes

Reaction equation

HRID 1611480 reaction equation
[Br:1][C:2]1[S:10][C:9]2[C:4](=[N:5][CH:6]=[C:7]([C:12]([O:14]CC)=[O:13])[C:8]=2[OH:11])[CH:3]=1.C(O)(=O)C>C(O)C.[OH-].[Na+]>[Br:1][C:2]1[S:10][C:9]2[C:4](=[N:5][CH:6]=[C:7]([C:12]([OH:14])=[O:13])[C:8]=2[OH:11])[CH:3]=1

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 178469487HCID 178469487, compound

Product 1

HCID 178524701HCID 178524701, compoundYield 71.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

A mixture of ethyl 2-bromo-7-hydroxythieno[3,2-b]pyridine-6-carboxylate (1.3 g, 4.3 mmol) [Elliott, R.; O'Hanlon, P. J.; Rodgers, N. B. Tetrahedron, 43(14), 3295 (1987)] in 20 mL of ethanol and 6 mL of 2.5 N sodium hydroxide is heated at reflux for 4 hours. The mixture is poured into ice water and the pH is adjusted to 5-6 by the addition of acetic acid. The mixture is stirred at room temperature and the resulting precipitate is collected by filtration washing with water to provide 840 mg of 2-bromo-7-hydroxythieno[3,2-b]pyridine-6-carboxylic acid. A mixture of 2-bromo-7-hydroxythieno[2,3-b]pyridine-6-carboxylic acid (810 mg, 2.95 mmol) and N,N-carbonyldiimidazole (1.0 g, 6.17 mmol) in 15 mL of N,N′-dimethylformamide is heated at 65° C. for 2 hours. The mixture is poured into 50 mL of ice cold aqueous ammonium hydroxide and stirred for 14 hours. The resultant solids are collected by filtration washing with water to provide 800 mg of 2-bromo-7-hydroxythieno[3,2-b]pyridine-6-carboxamide. A mixture of 2-bromo-7-hydroxythieno[3,2-b]pyridine-6-carboxamide (273 mg, 1.0 mmol) and 3 mL of phosphorous oxychloride is heated at reflux for 1 hour. The solvent is removed in vacuo and the residue is poured into ice water and treated with sodium bicarbonate. The resultant solids are collected by filtration washing with water. The solids are purified by flash column chromatography eluting with chloroform to provide 240 mg of 2-bromo-7-chlorothieno[3,2-b]pyridine-6-carbonitrile as yellow crystals, mp 198-199° C.; 1H NMR (DMSO-d6) δ 8.12 (s, 1H), 9.11 (s, 1H); MS 273.1, 275.1, 277.1 (M+H)+.

Workup

  1. temperatureis heated
  2. temperatureat reflux for 4 hours
  3. filtrationthe resulting precipitate is collected by filtration
  4. washwashing with water

Sources & evidence

ORD record
ord-b658184bbe05412a912c013686c776e2
Source dataset
uspto-grants-2006_01
Patent number
US06987116B2

Reaction notes

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