Methyl Isobutyl Ketone → 3-[2-(3,4-Dihydro-[1]benzothieno[3,2-c]pyridin-2(1h)-yl)ethyl]4h-pyrido[1,2-a]pyrimidin-4-one (e)-2-butenedioate

HRID 1835693Notes

Reaction equation

HRID 1835693 reaction equation
[CH2:1]1[C:6]2[C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=3[S:9][C:5]=2[CH2:4][CH2:3][NH:2]1.Cl[CH2:15][CH2:16][C:17]1[C:22](=[O:23])[N:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]2=[N:19][C:18]=1C.[C:29]([O-:32])([O-:31])=O.[Na+].[Na+].CC(CC(C)C)=[O:37]>>[C:22]([OH:23])(=[O:37])/[CH:17]=[CH:18]/[C:29]([OH:32])=[O:31].[CH2:1]1[C:6]2[C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=3[S:9][C:5]=2[CH2:4][CH2:3][N:2]1[CH2:15][CH2:16][C:17]1[C:22](=[O:23])[N:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]2=[N:19][CH:18]=1

Participants

5

Reactant 4

HCID 7909Methyl Isobutyl KetoneHCID 10340Sodium CarbonateHCID 8178663-(2-Chloroethyl)-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-oneHCID 113559561,2,3,4-Tetrahydro-benzo[4,5]thieno[3,2-c]pyridine

Product 1

HCID 1317245173-[2-(3,4-Dihydro-[1]benzothieno[3,2-c]pyridin-2(1h)-yl)ethyl]4h-pyrido[1,2-a]pyrimidin-4-one (e)-2-butenedioateYield 47%

Procedure

A mixture of 1,2,3,4-tetrahydro-benzothieno[3,2-c]pyridine [prepared analogous to the procedure described in J. Am. Chem. Soc., 1953, p. 697] (0.009 mol), 3-(2-chloro-ethyl)-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one (0.011 mol), Na2CO3 (0.023 mol) and KI (catalytic quantity) in methylisobutyl keton (100 ml) was stirred and refluxed overnight, then cooled to room temperature and the solvent was evaporated. The residue was washed with water and extracted with CH2Cl2. The separated organic layer was dried, filtered and the solvent evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 90/10). The desired fractions were collected and the solvent was evaporated. The residue was converted into the (E)-2-butenedioic acid salt (2:1). The precipitate was filtered off and dried, yielding 2.3 g (47%) of 3-[2-(3,4-dihydro-[1]benzothieno[3,2-c]pyridin-2(1H)-yl)ethyl]4H-pyrido[1,2-a]pyrimidin-4-one (E)-2-butenedioate(2:1) (comp. 1).

Workup

  1. customprepared analogous to the procedure
  2. temperaturerefluxed overnight
  3. customthe solvent was evaporated
  4. washThe residue was washed with water
  5. extractionextracted with CH2Cl2
  6. customThe separated organic layer was dried
  7. filtrationfiltered
  8. customthe solvent evaporated
  9. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 90/10)
  10. customThe desired fractions were collected
  11. customthe solvent was evaporated
  12. filtrationThe precipitate was filtered off
  13. customdried

Sources & evidence

ORD record
ord-f9dc3ba5a4cf49029008b22e86e921c9
Source dataset
uspto-grants-2004_08
Patent number
US06774129B2

Reaction notes

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