Sodium Bicarbonate → 6-[2-[4-[(2,4-difluorophenyl)(hydroxyimino)methyl]-1-piperazinyl]ethyl]-2,3-dihydro-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one

HRID 2051016Notes

Reaction equation

HRID 2051016 reaction equation
Br.Br[CH2:3][CH2:4][C:5]1[C:10](=[O:11])[N:9]2[CH2:12][CH2:13][S:14][C:8]2=[N:7][C:6]=1[CH3:15].[F:16][C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=1[C:24](=[N:31][OH:32])[N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.C(=O)([O-])O.[Na+]>CC(C)CC(=O)C>[F:16][C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=1[C:24](=[N:31][OH:32])[N:25]1[CH2:30][CH2:29][N:28]([CH2:3][CH2:4][C:5]2[C:10](=[O:11])[N:9]3[CH2:12][CH2:13][S:14][C:8]3=[N:7][C:6]=2[CH3:15])[CH2:27][CH2:26]1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 155864646-(2-bromoethyl)-2,3-dihydro-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one monohydrobromideHCID 545060241-[(2,4-Difluorophenyl)(hydroxyimino)methyl]piperazine

Product 1

HCID 542159526-[2-[4-[(2,4-difluorophenyl)(hydroxyimino)methyl]-1-piperazinyl]ethyl]-2,3-dihydro-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-oneYield 50.5%

Reagents, catalysts & solvents 1

HCID 7909Methyl Isobutyl KetoneSolvent

Procedure

A mixture of 8 parts of 6-(2-bromoethyl)-2,3-dihydro-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one monohydrobromide, 4.8 parts of 1-[(2,4-difluorophenyl)(hydroxyimino)methyl]piperazine, 8 parts of sodium hydrogen carbonate and 180 parts of 4-methyl-2-pentanone was stirred for 20 hours at reflux temperature. The reaction mixture was filtered while hot and the filtrate was evaporated in vacuo. 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 concentrated in vacuo. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 4.4 parts (50.5%) 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 (int. 13).

Workup

  1. temperatureat reflux temperature
  2. filtrationThe reaction mixture was filtered while hot and the filtrate
  3. customwas evaporated in vacuo
  4. customThe residue was purified by column chromatography over silica gel using
  5. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  6. customThe pure fractions were collected
  7. concentrationthe eluent was concentrated in vacuo
  8. customThe residue was crystallized from acetonitrile
  9. filtrationThe product was filtered off
  10. customdried

Sources & evidence

ORD record
ord-d00f6ec3af3842598f4f44a80a37e1d9
Source dataset
uspto-grants-1991_05
Patent number
US05015740

Reaction notes

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