Reaktion #324388

Reaktionsgleichung

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

Ausbeute 44.4%

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

Ausbeute 44.4%

Lösungsmittel

pyridine

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeprepared above at 0° C.
2. 2
   Temperaturthe mixture was heated
3. 3
   TemperaturAfter cooling to room temperature
4. 4
   Extraktionthe product was extracted with ethyl acetate (200 mL×3)
5. 5
   ExtraktionThe combined organic extract
6. 6
   Waschenwas washed successively with water (200 mL) and brine (200 mL)
7. 7
   Trocknenby drying over anhydrous sodium sulfate
8. 8
   FiltrationAfter filtration and concentration under reduced pressure
9. 9
   Sonstigethe residue was purified by column chromatography (silica gel 50 g, n-hexane/ethyl acetate=3/1)
10. 10
    SonstigeThe resulting solid was recrystallized (n-hexane/ethyl acetate)

Vorschrift

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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