Реакция #324388

Уравнение реакции

5-[4-(tert-butyldimethylsilyloxy)phenyl]-3-(thiophen-2-yl)pyrazin-2-amine

5-[4-(tert-Butyldimethylsilyloxy)phenyl]-3-(thiophen-2-yl)pyrazin-2-amine

2-[4-(tert-butyldimethylsilyloxy)phenyl]acetyl chloride

water

→

Compound 11f

Выход 44.4%

2-[4-(tert-Butyldimethylsilyloxy)phenyl]-N-[5-{4-(tert-butyldimethylsilyloxy)phenyl}-3-(thio phen-2-yl)pyrazin-2-yl]acetamide

Выход 44.4%

Растворители

pyridine

Условия реакции

Обработка

1. 1
   Другоеprepared above at 0° C.
2. 2
   Температураthe mixture was heated
3. 3
   ТемператураAfter cooling to room temperature
4. 4
   Экстракцияthe product was extracted with ethyl acetate (200 mL×3)
5. 5
   ЭкстракцияThe combined organic extract
6. 6
   Промывкаwas washed successively with water (200 mL) and brine (200 mL)
7. 7
   Сушкаby drying over anhydrous sodium sulfate
8. 8
   ФильтрацияAfter filtration and concentration under reduced pressure
9. 9
   Другоеthe residue was purified by column chromatography (silica gel 50 g, n-hexane/ethyl acetate=3/1)
10. 10
    ДругоеThe resulting solid was recrystallized (n-hexane/ethyl acetate)

Методика

Under an argon atmosphere, to a mixture of 5-[4-(tert-butyldimethylsilyloxy)phenyl]-3-(thiophen-2-yl)pyrazin-2-amine (7f) (600 mg, 1.59 mmol) and 4-(dimethylamino)pyridine (19.8 mg, 162 μmol) dissolved in anhydrous pyridine (20 mL) was added 2-[4-(tert-butyldimethylsilyloxy)phenyl]acetyl chloride (10) prepared above at 0° C. and the mixture was heated with stirring at 50° C. for 15 hours. After cooling to room temperature, to this was added water and the product was extracted with ethyl acetate (200 mL×3). The combined organic extract was washed successively with water (200 mL) and brine (200 mL), followed by drying over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was purified by column chromatography (silica gel 50 g, n-hexane/ethyl acetate=3/1). The resulting solid was recrystallized (n-hexane/ethyl acetate) to give Compound 11f (446 mg, 706 μmol, 44.4%) as a colorless solid. Rf=0.26 (n-hexane/diethyl ether=2/3); 1H NMR (400 MHz, DMSO-d6) δ 0.18 (s, 6H), 0.23 (s, 6H), 0.94 (s, 9H), 0.97 (s, 9H), 3.65 (s, 2H), 0.678-6.86 (AA′BB′, 2H), 6.97-7.06 (m, 3H, includes AA′BB′), 7.19-7.27 (AA′BB′, 2H), 7.51 (dd, 1H, J=0.9, 3.7 Hz), 7.69 (dd, 1H, J=0.9, 5.0 Hz), 8.06-8.14 (AA′BB′, 2H), 8.93 (s, 1H), 10.60 (s, 1H); 13C NMR (75.5 MHz, DMSO-d6) δ −4.6 (4C), 17.9, 18.0, 25.50 (3C), 25.54 (3C), 41.9, 119.6 (2C), 120.4 (2C), 127.8, 127.9, 128.0, 128.2 (2C), 128.4, 129.5, 130.5 (2C), 137.3, 140.5, 140.6, 142.5, 148.0, 153.9, 157.0, 170.3; IR (KBr, cm−1) 419, 519, 673, 704, 741, 781, 802, 839, 916, 1169, 1265, 1335, 1362, 1373, 1414, 1439, 1472, 1510, 1605, 1667, 2857, 2887, 2930, 2955, 3221; HRMS (ESI) m/z 654.2617 ([M+Na]+, C34H45N3NaO3Si2+ requires 654.2612).

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