Triethylamine → 2-(3-Chlorophenyl)-N-(2-pyridinyl)-3H-imidazo[4,5-b]pyridine-3acetamide

HRID 623044Notes

Reaction equation

HRID 623044 reaction equation
C(Cl)(=O)C(Cl)=O.[Cl:7][C:8]1[CH:9]=[C:10]([C:14]2[N:22]([CH2:23][C:24]([OH:26])=O)[C:17]3=[N:18][CH:19]=[CH:20][CH:21]=[C:16]3[N:15]=2)[CH:11]=[CH:12][CH:13]=1.[NH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1.C(N(CC)CC)C>CN(C)C=O>[Cl:7][C:8]1[CH:9]=[C:10]([C:14]2[N:22]([CH2:23][C:24]([NH:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=3)=[O:26])[C:17]3=[N:18][CH:19]=[CH:20][CH:21]=[C:16]3[N:15]=2)[CH:11]=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 104392-AminopyridineHCID 65578Oxalyl chlorideHCID 143904542-(3-Chlorophenyl)-3H-imidazo[4,5-b]pyridine-3-acetic acid

Product 1

HCID 143903222-(3-Chlorophenyl)-N-(2-pyridinyl)-3H-imidazo[4,5-b]pyridine-3acetamideYield 15.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Under a nitrogen atmosphere, oxalyl chloride (2.38 g, 0.019 mole) was added slowly dropwise to a stirred and chilled (15°-20° C.) solution of 2-(3-chlorophenyl)-3H-imidazo[4,5-b]pyridine-3-acetic acid (4.70 g, 0.016 mole) in 50 ml of dimethylformamide. The reaction mixture was stirred at ambient temperature for 1/2 hr., then warmed to 60°-65° C. for 5 hrs. This acylchloride solution was added dropwise under nitrogen to a stirred and chilled (15°-20° C.) solution of 2-aminopyridine (1.76 g, 0.019 mole), triethylamine (1.89 g, 0.019 mole), and 30 ml of dimethylformamide. The reaction mixture was stirred at room temperature over the weekend. The reaction mixture was poured into 400 ml of ice water and extracted with ethyl acetate (3×). The ethyl acetate layers were washed with 5% potassium hydroxide (2×60 ml), water (2×50 ml), dried, and filtered. The residue was treated with isopropyl alcohol and excess ethereal hydrogen chloride to give solid which was recrystallized twice from isopropyl alcohol-isopropyl ether and once from isopropyl alcohol. The solid was collected by filtration, washed with cold isopropyl alcohol, then isopropyl alcohol-water, and dried under high vacuum for 2 days to give 0.92 g (15.8%) of title compound, mp 165°-66° C.

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for 1/2 hr
  2. temperature, then warmed to 60°-65° C. for 5 hrs
  3. stirringa stirred
  4. stirringThe reaction mixture was stirred at room temperature over the weekend
  5. extractionextracted with ethyl acetate (3×)
  6. washThe ethyl acetate layers were washed with 5% potassium hydroxide (2×60 ml), water (2×50 ml)
  7. customdried
  8. filtrationfiltered
  9. additionThe residue was treated with isopropyl alcohol and excess ethereal hydrogen chloride
  10. customto give solid which
  11. customwas recrystallized twice from isopropyl alcohol-isopropyl ether and once from isopropyl alcohol
  12. filtrationThe solid was collected by filtration
  13. washwashed with cold isopropyl alcohol
  14. dry with materialisopropyl alcohol-water, and dried under high vacuum for 2 days

Sources & evidence

ORD record
ord-46391876865b471b852cd2ba137b078d
Source dataset
uspto-grants-1988_09
Patent number
US04772600

Reaction notes

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