反応 #50214

反応方程式

disodium ethylenediaminetetraacetic acid dihydrate

sodium carbonate

n-Butyllithium

1-methylimidazole

5-(5-bromo-2-ethoxyphenyl)-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one

→

title compound

収率 53.1%

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

収率 53.1%

溶媒

water

methanol

tetrahydrofuran

tetrahydrofuran

反応条件

後処理

1. 1
   温度the mixture heated
2. 2
   温度under reflux for 18 hours
3. 3
   温度the resulting mixture heated
4. 4
   温度under reflux for a further 60 hours
5. 5
   温度cooled
6. 6
   その他the solvent removed by evaporation under vacuum
7. 7
   抽出extracted with dichloromethane (6×100 ml)
8. 8
   乾燥dried (Na2SO4)
9. 9
   その他evaporated under vacuum
10. 10
    その他to give
11. 11
    その他a yellow solid, purification of which by chromatography on silica gel (13 g)
12. 12
    洗浄a methanol-dichloromethane elution gradient (0-3% methanol)
13. 13
    その他followed by crystallisation from ethyl acetate

実験手順

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%.

出典