Chloroform → HCID 178439976, compound

HRID 21863Notes

Reaction equation

HRID 21863 reaction equation
[CH2:1]([C:4]1[N:8]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]3[N:26](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:25]=[N:24][N:23]=3)=[CH:12][CH:11]=2)[CH:7]=[C:6]([CH2:46][CH2:47][NH2:48])[N:5]=1)[CH2:2][CH3:3].[OH2:49].C([O:54][CH2:55][CH3:56])(=O)C=O.Cl.[CH3:58][OH:59].[CH:60](Cl)(Cl)Cl.O1CC[CH2:66][CH2:65]1>>[CH2:1]([C:4]1[N:8]([CH2:9][C:10]2[CH:11]=[CH:12][C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]3[NH:26][N:25]=[N:24][N:23]=3)=[CH:14][CH:15]=2)[C:7]2[CH:60]([C:58]([O:54][CH2:55][CH3:56])=[O:59])[N:48]([C:65](=[O:49])[CH3:66])[CH2:47][CH2:46][C:6]=2[N:5]=1)[CH2:2][CH3:3]

Participants

6

Reactant 5

HCID 6212ChloroformHCID 8028TetrahydrofuranHCID 19932982HCID 19932982, compoundHCID 21893726Hydrochloride methanolHCID 22414697Ethyl glyoxylate hydrate

Product 1

HCID 178439976HCID 178439976, compoundYield 80%

Procedure

2-n-Propyl-5-(2-aminoethyl)-3-[2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methylimidazole (1.01g) is dissolved in tetrahydrofuran (10 ml), and thereto is added ethyl glyoxylate hydrate (195 mg), and the mixture is stirred at room temperature overnight. The mixture is heated at 50° C. for 30 minutes, and after cooling, 7% hydrochloric acid-methanol solution (3 ml) and chloroform (10 ml) are added to the mixture, which is refluxed for 20 minutes. The mixture is evaporated under reduced pressure to remove the solvent, and the resulting residue is dissolved in chloroform (30 ml). To the mixture are added acetic anhydride (290 mg) and a solution of sodium hydrogen carbonate (1.2 g) in water (20 ml), and the mixture is stirred at room temperature overnight. The mixture is acidified with citric acid, and extracted with chloroform. The extract is washed with water, dried, and evaporated. To the residue are added fumaric acid (100 mg) and ethanol (35 ml), and the mixture is refluxed for 5 hours. Then, the reaction mixture is evaporated under reduced pressure, and the residue is recrystallized from methanol/ether to give ethyl 2-n-propyl-5-acetyl-3-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl-4,5,6,7-tetrahydroimidazo[4,5-c]pyridine-4-carboxylate 1/2 fumarate (728 mg).

Workup

  1. temperatureThe mixture is heated at 50° C. for 30 minutes
  2. temperatureafter cooling
  3. temperatureis refluxed for 20 minutes
  4. customThe mixture is evaporated under reduced pressure
  5. customto remove the solvent
  6. dissolutionthe resulting residue is dissolved in chloroform (30 ml)
  7. additionTo the mixture are added acetic anhydride (290 mg)
  8. stirringa solution of sodium hydrogen carbonate (1.2 g) in water (20 ml), and the mixture is stirred at room temperature overnight
  9. extractionextracted with chloroform
  10. washThe extract is washed with water
  11. customdried
  12. customevaporated
  13. additionTo the residue are added fumaric acid (100 mg) and ethanol (35 ml)
  14. temperaturethe mixture is refluxed for 5 hours
  15. customThen, the reaction mixture is evaporated under reduced pressure
  16. customthe residue is recrystallized from methanol/ether

Sources & evidence

ORD record
ord-0c89ba16837e46ac9b770a71b541dd09
Source dataset
uspto-grants-1995_06
Patent number
US05424316

Reaction notes

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