Reaction #324414

Reaction equation

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

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

water

→

Compound 11s

Yield 74.8%

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

Yield 74.8%

Solvents

pyridine

Conditions

Workup

1. 1
   Otherprepared above at 0° C.
2. 2
   Temperaturethe mixture was heated
3. 3
   TemperatureAfter cooling to room temperature
4. 4
   Extractionthe product was extracted with ethyl acetate (200 mL×3)
5. 5
   ExtractionThe combined organic extract
6. 6
   Washwas washed successively with water (200 mL) and brine (200 mL)
7. 7
   Dryingby drying over anhydrous sodium sulfate
8. 8
   FiltrationAfter filtration and concentration under reduced pressure
9. 9
   Otherthe residue was purified by column chromatography (silica gel 50 g, n-hexane/ethyl acetate=7/1)

Procedure

Under an argon atmosphere, to a mixture of 5-[4-(tert-butyldimethylsilyloxy)phenyl]pyrazin-2-amine (7s) (350 mg, 1.16 mmol) and 4-(dimethylamino)pyridine (15.0 mg, 123 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 20 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=7/1) to give Compound 11s (478 mg, 869 μmol, 74.8%) as a yellow foamy solid. Rf=0.19 (n-hexane/ethyl acetate=6/1); 1H NMR (400 MHz, DMSO-d6) δ 0.14 (s, 6H), 0.19 (s, 6H), 0.91 (s, 9H), 0.94 (s, 9H), 3.66 (s, 2H), 6.75-6.82 (AA′BB′, 2H), 6.91-6.97 (AA′BB′, 2H), 7.17-7.24 (AA′BB′, 2H), 7.93-8.00 (AA′BB′, 2H), 8.90 (d, 1H, J=1.4 Hz), 9.28 (d, 1H, J=1.4 Hz), 10.99 (s, 1H); 13C NMR (75.5 MHz, DMSO-d6) δ −4.6 (4C), 17.8, 17.9, 25.46 (3C), 25.47 (3C), 41.8, 119.6 (2C), 120.2 (2C), 127.5 (2C), 128.2, 129.2, 130.4 (2C), 134.9, 138.7, 146.3, 147.0, 153.8, 156.2, 170.3; IR (KBr, cm−1) 417, 517, 575, 638, 681, 708, 781, 806, 839, 914, 1009, 1051, 1103, 1167, 1260, 1354, 1416, 1468, 1508, 1545, 1605, 1670, 2857, 2886, 2930, 2955, 3034, 3063; HRMS (ESI+) m/z 550.2930 ([M+H]+, C30H44N3O3Si2+ requires 550.2916).

Source