Acrylic Acid → HCID 13728656, compound

HRID 27074Notes

Reaction equation

HRID 27074 reaction equation
[C:1](O)(=[O:4])[CH:2]=[CH2:3].C1(N=C=NC2CCCCC2)CCCCC1.[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([N:28]2[CH:36]([O:37][C:38]([N:40]3[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]3)=[O:39])[C:35]3[C:30](=[N:31][CH:32]=[CH:33][N:34]=3)[C:29]2=[O:46])=[N:26][CH:27]=1>C(Cl)Cl.C(OCC)(=O)C.CN(C)C=O>[OH2:4].[C:1]([N:43]1[CH2:42][CH2:41][N:40]([C:38]([O:37][CH:36]2[C:35]3[C:30](=[N:31][CH:32]=[CH:33][N:34]=3)[C:29](=[O:46])[N:28]2[C:25]2[CH:24]=[CH:23][C:22]([Cl:21])=[CH:27][N:26]=2)=[O:39])[CH2:45][CH2:44]1)(=[O:4])[CH:2]=[CH2:3]

Participants

7

Reactant 3

HCID 6581Acrylic AcidHCID 10868DicyclohexylcarbodiimideHCID 162892N-Desmethylzopiclone

Product 1

HCID 13728656HCID 13728656, compoundYield 56.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent4×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

A solution of acrylic acid (1.19 g.) in anhydrous methylene chloride (10 cc.) followed by a solution of N,N'-dicyclohexylcarbodiimide (3.4 g.) in anhydrous methylene chloride (30 cc.) are added successively, at a temperature of about 20° C., to a suspension of 6-(5-chloropyrid-2-yl)-7-oxo-5-(piperazin-1-yl)carbonyloxy-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine (5.6 g.) in anhydrous methylene chloride (100 cc.). The mixture is stirred for 1 hour at a temperature of about 20° C. The insoluble product (dicyclohexylurea) is filtered off and washed with methylene chloride (2×10 cc.). The filtrate is concentrated to dryness under reduced pressure and then the residue obtained is taken up in ethyl acetate (25 cc.) and a small amount of insoluble matter is filtered off. The filtrate is left to stand for 18 hours at a temperature of about 20° C. and the product which has crystallised is filtered off and washed with ethyl acetate (3×2 cc.). After drying, the product obtained (4.9 g.) is dissolved in methylene chloride (100 cc.). The solution is filtered through silica gel (100 g.) contained in a column of diameter 3 cm. Elution is carried out using pure methylene chloride (400 cc.), a mixture of methylene chloride and methanol (99-1 by volume; 300 cc.) and a mixture of methylene chloride and methanol (98-2 by volume; 300 cc.). These eluates are discarded. Elution is then carried out using a mixture of methylene chloride and methanol (98-2 by volume; 200 cc.) and the corresponding eluates are combined and concentrated to dryness under reduced pressure (20 mm.Hg). After recrystallisation from acetonitrile and drying, a product (2.3 g.), which is solvated with acetonitrile, is obtained. This product is dissolved in dimethylformamide (37 cc.) at a temperature of about 50° C. and the solution is poured into ice-water (370 cc.). The insoluble product is filtered off and washed with water (3×10 cc.). After drying, 5-(4-acryloylpiperazin-1-yl)carbonyloxy-6-(5-chloropyrid-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine hydrate (2.08 g.), which melts at about 202°-204° C., is obtained.

Workup

  1. filtrationThe insoluble product (dicyclohexylurea) is filtered off
  2. washwashed with methylene chloride (2×10 cc.)
  3. concentrationThe filtrate is concentrated to dryness under reduced pressure
  4. customthe residue obtained
  5. filtrationa small amount of insoluble matter is filtered off
  6. waitThe filtrate is left
  7. waitto stand for 18 hours at a temperature of about 20° C.
  8. customthe product which has crystallised
  9. filtrationis filtered off
  10. washwashed with ethyl acetate (3×2 cc.)
  11. customAfter drying
  12. customthe product obtained (4.9 g.)
  13. filtrationThe solution is filtered through silica gel (100 g.)
  14. washElution
  15. additiona mixture of methylene chloride and methanol (99-1 by volume; 300 cc.)
  16. additiona mixture of methylene chloride and methanol (98-2 by volume; 300 cc.)
  17. washElution
  18. additiona mixture of methylene chloride and methanol (98-2 by volume; 200 cc.)
  19. concentrationconcentrated to dryness under reduced pressure (20 mm.Hg)
  20. customAfter recrystallisation from acetonitrile
  21. customdrying
  22. customis obtained
  23. filtrationThe insoluble product is filtered off
  24. washwashed with water (3×10 cc.)
  25. customAfter drying

Sources & evidence

ORD record
ord-2ccf4d75936449f5857ab838f4e676cc
Source dataset
uspto-grants-1980_09
Patent number
US04220646

Reaction notes

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