Methyl Isobutyl Ketone → 6-[2-[4-[2-(4-fluorophenyl)1,3-dioxolan-2-yl]-1-piperidinyl]ethyl]-3,7-dimethyl-5H-thiazolo[3,2-a]pyrimidin-5-one

HRID 325930Notes

Reaction equation

HRID 325930 reaction equation
Br.Br[CH2:3][CH2:4][C:5]1[C:10](=[O:11])[N:9]2[C:12]([CH3:15])=[CH:13][S:14][C:8]2=[N:7][C:6]=1[CH3:16].[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2([CH:29]3[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)[O:28][CH2:27][CH2:26][O:25]2)=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Na+].[Na+].CC(C)CC(=O)C>O>[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2([CH:29]3[CH2:34][CH2:33][N:32]([CH2:3][CH2:4][C:5]4[C:10](=[O:11])[N:9]5[C:12]([CH3:15])=[CH:13][S:14][C:8]5=[N:7][C:6]=4[CH3:16])[CH2:31][CH2:30]3)[O:28][CH2:27][CH2:26][O:25]2)=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 7909Methyl Isobutyl KetoneHCID 10340Sodium CarbonateHCID 132790992-(4-Fluorophenyl)-2-(4-piperidyl)1,3-dioxolaneHCID 139830776-(2-Bromoethyl)-3,7-dimethyl-5H-thiazolo[3,2-A]pyrimidin-5-one monohydrobromide

Product 1

HCID 134778126-[2-[4-[2-(4-fluorophenyl)1,3-dioxolan-2-yl]-1-piperidinyl]ethyl]-3,7-dimethyl-5H-thiazolo[3,2-a]pyrimidin-5-oneYield 35%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 9.3 parts of 6-(2-bromoethyl)-3,7-dimethyl-5H-thiazolo[3,2-a]pyrimidin-5-one monohydrobromide, 6.5 parts of 4-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]piperidine, 10.2 parts of sodium carbonate and 120 parts of 4-methyl-2-pentanone was stirred and refluxed overnight. The reaction mixture was cooled and water was added. The layers were separated. The organic phase was dried, filtered and evaporated. The residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (98:2 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 2,2'-oxybispropane. The product was filtered off and dried, yielding 4 parts (35%) of 6-[2-[4-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]-1-piperidinyl]ethyl]-3,7-dimethyl-5H-thiazolo[3,2-a]pyrimidin-5-one; mp. 140° C. (compound 35).

Workup

  1. temperaturerefluxed overnight
  2. temperatureThe reaction mixture was cooled
  3. customThe layers were separated
  4. customThe organic phase was dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column-chromatography over silica gel using
  8. additiona mixture of trichloromethane and methanol (98:2 by volume) as eluent
  9. customThe pure fractions were collected
  10. customthe eluent was evaporated
  11. customThe residue was crystallized from 2,2'-oxybispropane
  12. filtrationThe product was filtered off
  13. customdried

Sources & evidence

ORD record
ord-f2e91d30549543cd82e5f7f1a10c8700
Source dataset
uspto-grants-1984_04
Patent number
US04443451

Reaction notes

Loading…