تفاعل #439807
ord-d2dbdee227164ba6a80e7e80234f9332
معادلة التفاعل
الكواشف
المذيبات
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المعالجة
- 1أخرىThe above synthesis
- 2أخرىThe organic layer was separated
- 3أخرىthe solvent was removed in vacuo
- 4أخرىthe residue was chromatographed (ethyl acetate/hexane, 1/19)
الإجراء التجريبي
The above synthesis may be carried out as follows: To a solution of LDA (1.28 g, 12 mmol) in THF (30 mL) at −78° C. was added 2,4-dichloro-6-methylpyrimidine (1.96 g, 12 mmol) in THF (15 mL). After stirring for 15 minutes, 3,3-dimethylallyl bromide (1.79 g, 12 mmol) in THF (5 mL) was added dropwise. After the reaction warmed to ambient temperature, water and ethyl acetate was added. The organic layer was separated, the solvent was removed in vacuo, and the residue was chromatographed (ethyl acetate/hexane, 1/19) to give 2.06 g (74%) of 2,4-dichloro-6-(4-methyl-3-pentenyl)pyrimidine (1H NMR (CDCl3) δ7.15 (s, 1), 5.10 (t, 1), 2.80 (t, 2), 2.45 (m, 21, 1.70 (s, 3), 1.55 (s, 3)). To a solution of NaIO4 (17 g, 81 mmol) and KMnO4 (251 mg, 1.59 mmol) in water was added K2CO3 (1.29 g, 9.38 mmol) and 2,4dichloro-6-(4-methyl-3-pentenyl)pyrimidine (2.06 g, 8.9 mmol) in t-butanol. After stirring for 16 hours, the reaction was acidified to pH 3 and extracted with ethyl acetate. The organic layer was extracted with aqueous NaHCO3. The aqueous layer was acidified to pH 3 and extracted with ethyl acetate. The organic layer was dried and the solvent removed in vacuo to give 980 mg of 3-(2,4-dichloropyrimidin-6-yl)propionic acid (the compound of formula (XIX)), 1H NMR (CDCl3) δ7.30 (s, 1), 3.05 (t, 2), 2.90 (t, 2). The acid was coupled to piperonylamine under standard conditions with isobutyl chloroformate and N-methylmorpholine to give the compound of formula (XX). Imidazole was added under standard conditions (1-trimethylsilylimidazole and CsF in DMF at 60° C.) to give N-[(1,3-benzodioxol-5-yl)ethyl]-6-chloro-2-(1H-imidazol-1-yl)pyrimidine-4-propionamide (the compound of formula (Ihh)); MS: 386 (M+H)+.