Methane → HCID 13478595, compound

HRID 1788760Notes

Reaction equation

HRID 1788760 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.Cl[C:10]([C:12]1[CH:13]=[C:14]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)[N:15]2[C:19]=1[CH2:18][S:17][CH2:16]2)=[O:11].[OH-].[Na+].C>C(Cl)Cl.C(#N)C>[C:2]1([NH:1][C:10]([C:12]2[CH:13]=[C:14]([C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)[N:15]3[C:19]=2[CH2:18][S:17][CH2:16]3)=[O:11])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 297MethaneHCID 6115AnilineHCID 14798Sodium HydroxideHCID 20190397HCID 20190397, compound

Product 1

HCID 13478595HCID 13478595, compoundYield 57.8%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
20 °C

Procedure

A solution of aniline (11.2 g) in methylene chloride (50 cc) is added over 15 minutes at a temperature of about 24° C. and 29° C. to a suspension of 7-chloroformyl-5-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole hydrochloride (12 g) in methylene chloride (200 cc). The suspension obtained is stirred at a temperature of about 20° C. for 16 hours. Methylene chloride (300 cc) and distilled water (200 cc) are then added to the suspension. The insoluble material is separated off by filtration, washed 3 times with methylene chloride (75 cc in total) and 3 times with distilled water (75 cc in total). The mother-liquors from filtration and washing are combined; the organic phase is separated off, washed twice with distilled water (400 cc in total), once with a 2 N aqueous solution of sodium hydroxide (200 cc), then twice with distilled water (400 cc in total), dried over anhydrous magnesium sulphate, treated with decolourising charcoal (0.5 g) and filtered. A crude solution (625 cc) of product in methylene chloride is thus obtained. The insoluble material obtained earlier is taken up with a 5 N aqueous solution of sodium hydroxide (200 cc). The oil obtained is extracted 3 times with methylene chloride (750 cc in total). The organic extracts are combined, washed 3 times with distilled water (450 cc in total), dried over anhydrous magnesium sulphate, treated with decolourising charcoal (0.5 g) and filtered. The methylene chloride solution obtained is combined with the methylene chloride solution obtained earlier (625 cc) and the solvent is evaporated off under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 60° C. A crude product (15.4 g) is thus obtained. This product is dissolved in boiling acetonitrile (210 cc). The solution obtained is treated with decolourising charcoal (0.5 g) and filtered hot. The filtrate is cooled at a temperature of about 4° C. for 2 hours. The crystals which have appeared are separated off by filtration, washed 3 times with acetonitrile (30 cc in total) cooled to a temperature of about 4° C. and 3 times with isopropyl ether (75 cc in total) and are then dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 20° C. in the presence of potassium hydroxide pellets. N-phenyl-5-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxamide (7.4 g) is thus obtained in the form of cream crystals melting at 188° C.

Workup

  1. customThe suspension obtained
  2. distillationMethylene chloride (300 cc) and distilled water (200 cc)
  3. additionare then added to the suspension
  4. customThe insoluble material is separated off by filtration
  5. washwashed 3 times with methylene chloride (75 cc in total) and 3 times with distilled water (75 cc in total)
  6. filtrationThe mother-liquors from filtration
  7. washwashing
  8. customthe organic phase is separated off
  9. washwashed twice with distilled water (400 cc in total), once with a 2 N aqueous solution of sodium hydroxide (200 cc)
  10. dry with materialtwice with distilled water (400 cc in total), dried over anhydrous magnesium sulphate
  11. additiontreated with decolourising charcoal (0.5 g)
  12. filtrationfiltered
  13. customA crude solution (625 cc) of product in methylene chloride is thus obtained
  14. customThe insoluble material obtained earlier
  15. customThe oil obtained
  16. extractionis extracted 3 times with methylene chloride (750 cc in total)
  17. washwashed 3 times with distilled water (450 cc in total)
  18. dry with materialdried over anhydrous magnesium sulphate
  19. additiontreated with decolourising charcoal (0.5 g)
  20. filtrationfiltered
  21. customThe methylene chloride solution obtained
  22. customobtained earlier (625 cc)
  23. customthe solvent is evaporated off under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 60° C
  24. customA crude product (15.4 g) is thus obtained
  25. dissolutionThis product is dissolved
  26. customThe solution obtained
  27. filtrationfiltered hot
  28. temperatureThe filtrate is cooled at a temperature of about 4° C. for 2 hours
  29. customThe crystals which have appeared are separated off by filtration
  30. washwashed 3 times with acetonitrile (30 cc in total)
  31. temperaturecooled to a temperature of about 4° C. and 3 times with isopropyl ether (75 cc in total)
  32. dry with materialare then dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 20° C. in the presence of potassium hydroxide pellets

Sources & evidence

ORD record
ord-4a4238247c624393b3e38a48addec651
Source dataset
uspto-grants-1987_08
Patent number
US04684658

Reaction notes

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