Acetonitrile → HCID 21285567, compound

HRID 2231758Notes

Reaction equation

HRID 2231758 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].[NH2:19][C:20]1[CH:21]=[C:22]([CH:36]=[CH:37][CH:38]=1)[C:23]([C:25]1[CH:35]=[CH:34][CH:33]=[CH:32][C:26]=1[C:27]([O:29][CH2:30][CH3:31])=[O:28])=[O:24].C(N(CC)CC)C.C(#N)C>O1CCOCC1>[CH2:30]([O:29][C:27]([C:26]1[CH:32]=[CH:33][CH:34]=[CH:35][C:25]=1[C:23]([C:22]1[CH:21]=[C:20]([NH:19][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:38]=[CH:37][CH:36]=1)=[O:24])=[O:28])[CH3:31]

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 8471TriethylamineHCID 199113037-chloroformyl-3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole hydrochlorideHCID 21285585HCID 21285585, compound

Product 1

HCID 21285567HCID 21285567, compoundYield 14.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

7-Chloroformyl-3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole hydrochloride (5.1 g) is added, at a temperature between 70° and 78° C., to a solution of ethyl 2-(3'-aminobenzoyl)benzoate (4.6 g) and triethylamine (3.45 g) in dioxane (150 cc) which is heated to a temperature in the vicinity of 70° 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 45 minutes and 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 (300 cc). The solution obtained is washed twice with distilled water (300 cc in total), twice with a saturated aqueous sodium bicarbonate solution (300 cc in total) and twice with distilled water (300 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 60° C. A crude product (9 g) is thereby obtained, which is chromatographed on an 8 cm diameter column containing silica (0.02-0.045 mm; 640 g). Elution is carried out with ethyl acetate at a pressure of 0.45 bar (45 kPa), collecting 300 cm fractions. The first 12 fractions are discarded. The following 6 fractions are combined and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 50° C. A crude product (5.1 g) is thereby obtained, which is dissolved in boiling acetonitrile (30 cc). The solution obtained is filtered in the heated state. The filtrate obtained is cooled at a temperature in the vicinity of 4° C. for 1 hour. The crystals formed are separated by filtration, washed 3 times with acetonitrile cooled to a temperature in the vicinity of 4° C. (30 cc in total) and 3 times with diethyl ether (90 cc in total) and the 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-(2-ethoxycarbonylbenzoyl)phenyl]-3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxamide (1.2 g) in the form of cream-coloured crystals, m.p. 150° C., is thereby obtained.

Workup

  1. customThe suspension obtained
  2. temperatureis heated
  3. stirringstirred 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 (300 cc)
  6. customThe solution obtained
  7. washis washed twice with distilled water (300 cc in total), twice with a saturated aqueous sodium bicarbonate solution (300 cc in total) and twice with distilled water (300 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 60° C
  12. customA crude product (9 g) is thereby obtained
  13. customwhich is chromatographed on an 8 cm diameter column
  14. additioncontaining silica (0.02-0.045 mm; 640 g)
  15. washElution
  16. customcollecting 300 cm fractions
  17. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 50° C
  18. customA crude product (5.1 g) is thereby obtained
  19. dissolutionwhich is dissolved
  20. customThe solution obtained
  21. filtrationis filtered in the heated state
  22. customThe filtrate obtained
  23. temperatureis cooled at a temperature in the vicinity of 4° C. for 1 hour
  24. customThe crystals formed
  25. customare separated by filtration
  26. washwashed 3 times with acetonitrile
  27. temperaturecooled to a temperature in the vicinity of 4° C. (30 cc in total) and 3 times with diethyl ether (90 cc in total)
  28. dry with materialthe 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-4f0e26894fcc484086c30c311bb642dd
Source dataset
uspto-grants-1988_11
Patent number
US04783472

Reaction notes

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