Acetonitrile → HCID 21285574, compound

HRID 2231746Notes

Reaction equation

HRID 2231746 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:31]=[CH:32][CH:33]=1)[C:23]([C:25]1[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=1)=[O:24].C(N(CC)CC)C.C(#N)C>O1CCOCC1>[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:33]=[CH:32][CH:31]=1)(=[O:24])[C:25]1[CH:30]=[CH:29][CH:28]=[N:27][CH:26]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 8471TriethylamineHCID 12930028(3-Aminophenyl)-3-pyridinylmethanoneHCID 199113037-chloroformyl-3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole hydrochloride

Product 1

HCID 21285574HCID 21285574, compoundYield 50.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

7-Chloroformyl-3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole hydrochloride (6.9 g) is added, at a temperature between 50° and 85° C., to a solution of 3-(3-aminobenzoyl)pyridine (5.75 g) and triethylamine (4.65 g) in dioxane (120 cc) which is heated to a temperature in the vicinity of 50° C., in the course of 25 minutes. The suspension obtained is heated, with stirring, at a temperature in the vicinity of 100° C. for 6 hours 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 (350 cc) and the solution obtained is washed twice with distilled water (200 cc in total), twice with an aqueous 2N sodium hydroxide solution (200 cc in total) and 3 times with distilled water (450 cc) 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. The product obtained is chromatographed on an 8 cm diameter column containing silica (0.02-0.045 mm; 500 g). Elution is carried out with mixtures of ethyl acetate and methanol at a pressure of 0.4 bar (40 kPa), collecting 500 cc fractions. The first 19 fractions originating from elution with pure ethyl acetate are discarded. The following 2 fractions originating from elution with pure ethyl acetate and the following 2 fractions originating from elution with an ethyl acetate:methanol (90:10 by volume) mixture 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 (8 g) is thereby obtained. This product is dissolved in boiling acetonitrile (50 cc). Decolourizing chacoal (0.5 g) is added to the solution obtained and the suspension 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 twice with acetonitrile cooled to a temperature in the vicinity of 4° C. (20 cc in total) and twice with diethyl ether (40 cc in total) and then 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-nicotinoyl- phenyl)-3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxamide (4.9 g) in the form of cream-coloured crystals, m.p. 160° 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 (350 cc)
  6. customthe solution obtained
  7. washis washed twice with distilled water (200 cc in total), twice with an aqueous 2N sodium hydroxide solution (200 cc in total) and 3 times with distilled water (450 cc)
  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. customThe product obtained
  13. customis chromatographed on an 8 cm diameter column
  14. additioncontaining silica (0.02-0.045 mm; 500 g)
  15. washElution
  16. customcollecting 500 cc fractions
  17. washThe first 19 fractions originating from elution with pure ethyl acetate
  18. washThe following 2 fractions originating from elution with pure ethyl acetate
  19. washthe following 2 fractions originating from elution with an ethyl acetate:methanol (90:10 by volume) mixture
  20. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 50° C
  21. customA crude product (8 g) is thereby obtained
  22. dissolutionThis product is dissolved
  23. additionDecolourizing chacoal (0.5 g) is added to the solution
  24. customobtained
  25. filtrationthe suspension is filtered in the heated state
  26. customThe filtrate obtained
  27. temperatureis cooled at a temperature in the vicinity of 4° C. for 1 hour
  28. customThe crystals formed
  29. customare separated by filtration
  30. washwashed twice with acetonitrile
  31. temperaturecooled to a temperature in the vicinity of 4° C. (20 cc in total) and twice with diethyl ether (40 cc in total)
  32. dry with materialdried 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-9009f7946d0142dcad5b8cd3b8447ad6
Source dataset
uspto-grants-1988_11
Patent number
US04783472

Reaction notes

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