反应详情

To a solution of Boc-Asn(Trt)-OH (100.4 mg, 0.2116 mmol) in acetonitrile (2.0 mL) cooled in an ice water bath was added 4-methylmorpholine (0.059 mL, 0.53 mmol) and isobutyl chloroformate (0.027 mL, 0.21 mmol). After stirring for 60 minutes, 3′,4′-diamino-3-fluoro-[1,1-biphenyl]-4-carbonitrile (Preparation 81, 42.7 mg, 0.188 mmol) was added and the mixture allowed to warm to room temperature. After stirring for 18 hours the reaction mixture was concentrated in vacuo and redissolved in acetic acid. After stirring at room temperature for 6.5 hours, the mixture was concentrated in vacuo, redissolved in ethyl acetate, washed with water, 0.5M HCl, and brine. The organic layer was dried over anhydrous magnesium sulphate, filtered, and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with a 0-100% ethyl acetate/hexanes gradient to afford the title compound (75 mg, 60%).

1. stirringAfter stirring for 18 hours the reaction mixture
2. concentrationwas concentrated in vacuo
3. dissolutionredissolved in acetic acid
4. stirringAfter stirring at room temperature for 6.5 hours
5. concentrationthe mixture was concentrated in vacuo
6. dissolutionredissolved in ethyl acetate
7. washwashed with water, 0.5M HCl, and brine
8. dry with materialThe organic layer was dried over anhydrous magnesium sulphate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe residue was purified
12. washeluting with a 0-100% ethyl acetate/hexanes gradient