Methane → N-(3-phenoxyphenyl)-3(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxamide

HRID 2231734Notes

Reaction equation

HRID 2231734 reaction equation
Cl.Cl[C:3]([C:5]1[CH:6]=[CH:7][N:8]2[C:12]=1[CH2:11][S:10][CH:9]2[C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)=[O:4].[O:19]([C:26]1[CH:27]=[C:28]([CH:30]=[CH:31][CH:32]=1)[NH2:29])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(N(CC)CC)C.C>O1CCOCC1.C(O)(C)C>[O:19]([C:26]1[CH:27]=[C:28]([NH:29][C:3]([C:5]2[CH:6]=[CH:7][N:8]3[C:12]=2[CH2:11][S:10][CH:9]3[C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)=[O:4])[CH:30]=[CH:31][CH:32]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

7

Reactant 4

HCID 297MethaneHCID 8471TriethylamineHCID 771353-PhenoxyanilineHCID 199113037-chloroformyl-3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole hydrochloride

Product 1

HCID 9823039N-(3-phenoxyphenyl)-3(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxamideYield 34%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

7-chloroformyl-3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole hydrochloride (4.5 g) is added, at a temperature between 60° C. and 68° C., to a solution of 3-phenoxyaniline (2.8 g) and triethylamine (3.05 g) in dioxane (100 cc) heated to a temperature in the vicinity of 60° C., in the course of 5 minutes. The suspension obtained is heated, with stirring, at a temperature in the vicinity of 100° C. for 6 hours and 15 minutes and is then stirred at a temperature in the vicinity of 20° C. for 16 hours. The solvent is evaporated off under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 60° C. The residue is dissolved in methylene chloride (250 cc) and the solution obtained is washed twice with distilled water (200 cc in total), twice with an aqueous 4N sodium hydroxide solution (200 cc in total) and twice with distilled water (200 cc in total) and then dried over anhydrous magnesium sulphate, treated with decolourizing charcoal (0.5 g), filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 50° C. Crude product (6.7 g) is thereby obtained. This product is dissolved in boiling isopropanol (25 cc). Decolourizing charcoal (0.5 g) is added to the solution obtained and the suspension is filtered in the heated state. The filtrate is cooled at a temperature in the vicinity of 4° C. for 3 hours. The crystals formed are separated by filtration, washed 4 times with ispropanol (20 cc in total) and then 3 times with diethyl ether (75 cc in total) and dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 20° C. in the presence of potassium hydroxide pellets. N-(3-phenoxyphenyl)-3(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxamide (2.1 g) in the form of creamcoloured crystals, m.p. 144° C., is thereby obtained.

Workup

  1. customThe suspension obtained
  2. temperatureis heated
  3. stirringis then stirred at a temperature in the vicinity of 20° C. for 16 hours
  4. customThe solvent is evaporated off under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 60° C
  5. dissolutionThe residue is dissolved in methylene chloride (250 cc)
  6. customthe solution obtained
  7. washis washed twice with distilled water (200 cc in total), twice with an aqueous 4N sodium hydroxide solution (200 cc in total) and twice with distilled water (200 cc in total)
  8. dry with materialdried over anhydrous magnesium sulphate
  9. additiontreated with decolourizing charcoal (0.5 g)
  10. filtrationfiltered
  11. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 50° C
  12. customCrude product (6.7 g) is thereby obtained
  13. dissolutionThis product is dissolved
  14. customobtained
  15. filtrationthe suspension is filtered in the heated state
  16. temperatureThe filtrate is cooled at a temperature in the vicinity of 4° C. for 3 hours
  17. customThe crystals formed
  18. customare separated by filtration
  19. washwashed 4 times with ispropanol (20 cc in total)
  20. dry with material3 times with diethyl ether (75 cc in total) and dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 20° C. in the presence of potassium hydroxide pellets

Sources & evidence

ORD record
ord-9a04606a4aff4d90a7ba82cd3cf18228
Source dataset
uspto-grants-1988_11
Patent number
US04783472

Reaction notes

Loading…