反应 #324398

ord-18bba774a3814f2d8a9f4a7d72ee16cd

反应方程式

CC(C)(C)[Si](C)(C)Oc1ccc(-c2cnc(N)c(-c3cc4sccc4s3)n2)cc1
5-[4-(tert-butyldimethylsilyloxy)phenyl]-3-(thieno[3,2-b]thiophen-2-yl)pyrazin-2-amine
CC(C)(C)[Si](C)(C)Oc1ccc(-c2cnc(N)c(-c3cc4sccc4s3)n2)cc1
5-[4-(tert-Butyldimethylsilyloxy)phenyl]-3-(thieno[3,2-b]thiophen-2-yl)pyrazin-2-amine
CC(C)(C)[Si](C)(C)Oc1ccc(CC(=O)Cl)cc1
2-[4-(tert-butyldimethylsilyloxy)phenyl]acetyl chloride
O
water
CC(C)(C)[Si](C)(C)Oc1ccc(CC(=O)Nc2ncc(-c3ccc(O[Si](C)(C)C(C)(C)C)cc3)nc2-c2cc3sccc3s2)cc1
Compound 11k
收率 58.2%
CC(C)(C)[Si](C)(C)Oc1ccc(CC(=O)Nc2ncc(-c3ccc(O[Si](C)(C)C(C)(C)C)cc3)nc2-c2cc3sccc3s2)cc1
2-[4-(tert-Butyldimethylsilyloxy)phenyl]-N-[5-{4-(tert-butyldimethylsilyloxy)phenyl}-3-(thieno[3,2-b]thiophen-2-yl)pyrazin-2-yl]acetamide
收率 58.2%

溶剂

反应条件

温度
50°CELSIUS
详细条件
See reaction.notes.procedure_details.

后处理

  1. 1
    其他prepared above at 0° C.
  2. 2
    温度the mixture was heated
  3. 3
    温度After cooling to room temperature
  4. 4
    萃取the product was extracted with ethyl acetate (100 mL×3)
  5. 5
    萃取The combined organic extract
  6. 6
    洗涤was washed successively with water (200 mL) and brine (200 mL)
  7. 7
    干燥by drying over anhydrous sodium sulfate
  8. 8
    过滤After filtration and concentration under reduced pressure
  9. 9
    其他the residue was purified by column chromatography (silica gel 30 g, n-hexane/ethyl acetate=3/1)

实验过程

Under an argon atmosphere, to a mixture of 5-[4-(tert-butyldimethylsilyloxy)phenyl]-3-(thieno[3,2-b]thiophen-2-yl)pyrazin-2-amine (7k) (250 mg, 569 μmol and 4-(dimethylamino)pyridine (12.3 mg, 101 μmol) dissolved in anhydrous pyridine (15 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 13 hours. After cooling to room temperature, to this was added water and the product was extracted with ethyl acetate (100 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 30 g, n-hexane/ethyl acetate=3/1) to give Compound 11k (228 mg, 331 μmol, 58.2%) as a yellow solid. Rf=0.26 (n-hexane/ethyl acetate=3/1); 1H NMR (400 MHz, DMSO-d6) δ 0.17 (s, 6H), 0.22 (s, 6H), 0.93 (s, 9H), 0.95 (s, 9H), 3.67 (s, 2H), 6.78-6.86 (AA′BB′, 2H), 6.96-7.04 (AA′BB′, 2H), 7.20-7.30 (AA′BB′, 2H), 7.41 (d, 1H, J=5.2 Hz), 7.57 (s, 1H), 7.73 (d, 1H, J=5.2 Hz), 8.04-8.13 (AA′BB′, 2H), 8.92 (s, 1H), 10.69 (s, 1H); IR (KBr, cm−1) 527, 635, 702, 779, 837, 918, 1007, 1074, 1169, 1256, 1362, 1445, 1508, 1603, 1655, 2857, 2886, 2928, 2955, 3211.

来源

DOI: 10.6084/m9.figshare.5104873.v1专利: US08642281B2uspto-grants-2014_02