Реакция #70576

Уравнение реакции

5-bromo-2-phenylpyrimidine

4-Iodo-1-trityl-1H-imidazole

ethylmagnesium bromide

→

2-phenyl-5-(1-trityl-1H-imidazol-4-yl)pyrimidine

Растворители

dichloromethane

THF

Условия реакции

Обработка

1. 1
   workup.STIRRINGAfter stirring for an additional 90 minutes
2. 2
   ТемператураUpon cooling
3. 3
   Промывкаwashed with 0.5 M EDTA buffer (at pH ˜9) (2×250 mL)
4. 4
   СушкаThe organics were dried over sodium sulfate
5. 5
   Фильтрацияfiltered
6. 6
   Концентрированиеconcentrated
7. 7
   ДругоеThe crude product was purified by flash silica column chromatography
8. 8
   Промывкаan 80 g Silicycle® column (elution with 10-30% ethyl acetate in hexane) which

Методика

To a solution of 4-Iodo-1-trityl-1H-imidazole (Synthonix, 2.0 g, 4.58 mmol) in THF (50 mL) at room temperature was added ethylmagnesium bromide (Aldrich, 1.0 M solution in THF, 5.5 mL, 5.50 mmol) under dry conditions. After stirring for 90 minutes, zinc chloride (Aldrich, 0.749. g, 5.50 mmol) was added to the reaction mixture. After stirring for an additional 90 minutes, tetrakis(triphenyl)phosphine)palladium (Strem, 0.529 g, 0.46 mmol) and 5-bromo-2-phenylpyrimidine (as prepared in Example 1, step A, 1.29 g, 5.50 mmol) were added to the reaction mixture. The reaction mixture was heated in a 70° C. oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane and washed with 0.5 M EDTA buffer (at pH ˜9) (2×250 mL) followed by brine (150 mL). The organics were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by flash silica column chromatography using an 80 g Silicycle® column (elution with 10-30% ethyl acetate in hexane) which afforded the desired intermediate, 2-phenyl-5-(1-trityl-1H-imidazol-4-yl)pyrimidine, as a white solid (1.38 g, 65%). Rf 0.87 with 95:5 v/v dichloromethane-methanol; 1H-NMR (400 MHz; DMSO-d6) δ 9.29 (s, 2H), 8.42 (m, 2H), 7.92 (d, 1H), 7.62 (d, 1H), 7.56-7.43 (m, 13H), 7.24-7.22 (m, 6H); MS (ESI−) m/z 463.0 (M−1); H-PGDS FPBA IC50: >20 μM.

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