Tetrahydrofuran → 6-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperazinyl]-ethyl]-2,3-dihydro-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one

HRID 1032297Notes

Reaction equation

HRID 1032297 reaction equation
F[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9](=[N:29][OH:30])[N:10]1[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][C:18]2[C:23](=[O:24])[N:22]3[CH2:25][CH2:26][S:27][C:21]3=[N:20][C:19]=2[CH3:28])[CH2:12][CH2:11]1.O1CCCC1.[H-].[Na+].[OH-].[NH4+]>C(O)(=O)C.C(O)C.CC1C=CC=CC=1>[F:8][C:6]1[CH:5]=[CH:4][C:3]2[C:9]([N:10]3[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][C:18]4[C:23](=[O:24])[N:22]5[CH2:25][CH2:26][S:27][C:21]5=[N:20][C:19]=4[CH3:28])[CH2:12][CH2:11]3)=[N:29][O:30][C:2]=2[CH:7]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 14923Ammonium HydroxideHCID 24758Sodium hydrideHCID 542159526-[2-[4-[(2,4-difluorophenyl)(hydroxyimino)methyl]-1-piperazinyl]ethyl]-2,3-dihydro-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one

Product 1

HCID 150574626-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperazinyl]-ethyl]-2,3-dihydro-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-oneYield 91.4%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

A solution of 4.4 parts of 6-[2-[4-[(2,4-difluorophenyl)(hydroxyimino)methyl]-1-piperazinyl]ethyl]-2,3-dihydro-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one in 45 parts of tetrahydrofuran was stirred at room temperature. 0.5 Parts of a sodium hydride dispersion 50% were added portionwise. Upon complete addition, 108 parts of methylbenzene were added and the reaction mixture was stirred for 18 hours at reflux temperature. After cooling, 16 parts of ethanol were added, followed by the addition of 3 parts of acetic acid. The whole was stirred for 10 minutes. The mixture was treated with ammonium hydroxide and the product was extracted with 4-methyl-2-pentanone. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 3.8 parts (91.4%) of 6-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperazinyl]ethyl]-2,3-dihydro-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one; mp. 193.0° C. (compound 3).

Workup

  1. additionwere added
  2. temperatureat reflux temperature
  3. temperatureAfter cooling
  4. stirringThe whole was stirred for 10 minutes
  5. extractionthe product was extracted with 4-methyl-2-pentanone
  6. customThe extract was dried
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by column chromatography over silica gel using
  10. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  11. customThe pure fractions were collected
  12. customthe eluent was evaporated
  13. customThe residue was crystallized from acetonitrile
  14. filtrationThe product was filtered off
  15. customdried

Sources & evidence

ORD record
ord-8c7fa969d04d42008ac6747b19fe1753
Source dataset
uspto-grants-1990_09
Patent number
US04957916

Reaction notes

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