反应详情

Add oxalyl chloride (0.20 mL, 2.30 mmol) and 4 drops of DMF to a stirring suspension of 4′-fluoro-biphenyl-4-carboxylic acid (0.243 g, 1.13 mmol) in CH2Cl2 (5.0 mL). Stir the reaction mixture at room temperature for 2 h. Concentrate the mixture in vacuo, add n-hexane, re-concentrate, and re-dissolve in CH2Cl2. Add the resultant 4′-fluoro-biphenyl-4-carbonyl chloride solution to a mixture of rac-N-{2-[(6-amino-benzothiazol-2-yl)-methyl-amino]-ethyl}-N-methyl-acetamide (0.146 g, 0.524 mmol) and pyridine (0.06 mL) in CH2Cl2 (10 mL). Shake the reaction mixture overnight at room temperature. Subject the residue to silica gel flash column chromatography (3×4 g columns, eluting with 5-10% ethyl acetate/n-hexane to remove impurities, then flushing off product with 2N NH3/MeOH). Triturate the residue with CH2Cl2 to yield the desired product as a white solid (0.110 g, 44%). mass spectrum (m/e): 477.0 (M+1).

1. concentrationConcentrate the mixture in vacuo
2. additionadd n-hexane
3. concentrationre-concentrate
4. dissolutionre-dissolve in CH2Cl2
5. additionAdd the resultant 4′-fluoro-biphenyl-4-carbonyl chloride solution
6. customthe reaction mixture overnight
7. customat room temperature
8. washeluting with 5-10% ethyl acetate/n-hexane
9. customto remove impurities
10. customflushing off product with 2N NH3/MeOH)
11. customTriturate the residue with CH2Cl2