1-Methylimidazole → 5-[2-Ethoxy-5-(1-methyl-2-imidazolyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one

HRID 21936

Reaktionsgleichung

Reaktionsgleichung von HRID 21936
C([Li])CCC.[CH3:6][N:7]1[CH:11]=[CH:10][N:9]=[CH:8]1.Br[C:13]1[CH:14]=[CH:15][C:16]([O:33][CH2:34][CH3:35])=[C:17]([C:19]2[NH:20][C:21](=[O:32])[C:22]3[N:27]([CH3:28])[N:26]=[C:25]([CH2:29][CH2:30][CH3:31])[C:23]=3[N:24]=2)[CH:18]=1.O.O.C(N(CC(O)=O)CC(O)=O)CN(CC(O)=O)CC(O)=O.[Na].[Na].C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.O.[Cl-].[Zn+2].[Cl-].CO>[CH2:34]([O:33][C:16]1[CH:15]=[CH:14][C:13]([C:8]2[N:7]([CH3:6])[CH:11]=[CH:10][N:9]=2)=[CH:18][C:17]=1[C:19]1[NH:20][C:21](=[O:32])[C:22]2[N:27]([CH3:28])[N:26]=[C:25]([CH2:29][CH2:30][CH3:31])[C:23]=2[N:24]=1)[CH3:35]

Komponenten

10

Edukt 5

HCID 13901-MethylimidazoleHCID 10340Sodium CarbonateHCID 86660564Disodium ethylenediaminetetraacetic acid dihydrateHCID 1357385545-(5-Bromo-2-ethoxyphenyl)-1-methyl-3-propyl-1H-pyrazolo[4,3-D]pyrimidin-7(6H)-oneHCID 178418339Butyllithium

Produkt 1

HCID 1355155045-[2-Ethoxy-5-(1-methyl-2-imidazolyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-oneAusbeute 53,1 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 3007855ZincchlorideKatalysator2×HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

n-Butyllithium (1.6M solution in hexane, 9.6 ml, 0.0153 mol) was added to a stirred solution of 1-methylimidazole (0.628 g, 0.0077 mol) in dry tetrahydrofuran (10 ml) at -78° C., and the resulting solution stirred for 0.25 hours. A solution of anhydrous zinc chloride (2.08 g, 0.0153 mol) in dry tetrahydrofuran (15 ml) was added, the mixture allowed to warm to room temperature, then 5-(5-bromo-2-ethoxyphenyl)-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (1.0 g, 0.0026 mol) and tetrakis(triphenylphospine)palladium(0) (0.036 g, 0.031 mmol) were added and the mixture heated under reflux for 18 hours. A further quantity of anhydrous zinc chloride (2.08 g, 0.0153 mol) was added and the resulting mixture heated under reflux for a further 60 hours, then cooled; methanol (2 ml) was added and the solvent removed by evaporation under vacuum. The residue was heated with a solution of disodium ethylenediaminetetraacetic acid dihydrate (23.0 g, 0.0618 mol) in water (100 ml) to 100° C. for 0.2 hour, then the resulting solution basified to pH 8 with saturated aqueous sodium carbonate solution and extracted with dichloromethane (6×100 ml). The organic extracts were combined, dried (Na2SO4) and evaporated under vacuum to give a yellow solid, purification of which by chromatography on silica gel (13 g), using a methanol-dichloromethane elution gradient (0-3% methanol), followed by crystallisation from ethyl acetate, gave the title compound as an off-white solid (0.542 g, 53%), m.p. 199°-202° C. Found: C,64.45; H,6.27; N,21.56. C21H24N6O2 requires C,64.27; H,6.16; N,21.42%.

Aufarbeitung

  1. temperaturethe mixture heated
  2. temperatureunder reflux for 18 hours
  3. temperaturethe resulting mixture heated
  4. temperatureunder reflux for a further 60 hours
  5. temperaturecooled
  6. customthe solvent removed by evaporation under vacuum
  7. extractionextracted with dichloromethane (6×100 ml)
  8. dry with materialdried (Na2SO4)
  9. customevaporated under vacuum
  10. customto give
  11. customa yellow solid, purification of which by chromatography on silica gel (13 g)
  12. washa methanol-dichloromethane elution gradient (0-3% methanol)
  13. customfollowed by crystallisation from ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-80c590cfcb37482f9074fa3dd6e0caa7
Quelldatensatz
uspto-grants-1995_06
Patentnummer
US05426107

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