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

반응식

HRID 21936 반응식
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]

참가 물질

10

반응물 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

생성물 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-one수율 53.1%

시약·촉매·용매 4

HCID 3007855Zincchloride촉매2회HCID 887Methanol용매HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

실험 절차

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%.

후처리

  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

출처 및 근거

ORD 기록
ord-80c590cfcb37482f9074fa3dd6e0caa7
출처 데이터셋
uspto-grants-1995_06
특허 번호
US05426107

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