反应详情

4-[[4-(aminoiminomethyl)phenyl]amino]-4-oxobutanoic acid hydrochloride prepared in Example 1, Step 1(3.0 g, 11.3 mmol) was added to dry DMF (200 ml) followed by N-methylmorpholine (1.2 g, 11.3 mmol) and isobutyl chloroformate (1.5 g, 17 mmol) at 25° C. The mixture was stirred for 5 min. 3-Amino-4-phenylsulfonyl butanoic acid (4.0 g, 11.3 mmol) was added followed by triethylamine (2.7 g) and dimethylaminopyridine. After 1 hr, the solvent was removed under reduced pressure and the solid mass was dissolved into a mixture of acetic acid:H2O:H2O2 30% (2:2:1) and stirred at 25° C. for 48 hr. The reaction mixture was concentrated in vacuo and the residue purified by reverse phase chromatography (0.05% TFA water/acetonitrile) to result in 3.5 g of a white solid: 1H NMR (d6-DMSO) 2.25 (m, 2H), 2.53 (m, 4H), 3.55 (m, 2H), 4.33 (m, 1H), 7.44 (m, 5H), 7.79 (s, 4H), 7.99 (d, 1H,J=8.1 Hz), 9.1 (bs, 2H), 9.19 (bs, 2H), 10.42 (s, 1H); MS (FAB) m/z 461.2 (MH+).

1. waitAfter 1 hr
2. customthe solvent was removed under reduced pressure
3. dissolutionthe solid mass was dissolved into a mixture of acetic acid
4. stirringH2O:H2O2 30% (2:2:1) and stirred at 25° C. for 48 hr
5. concentrationThe reaction mixture was concentrated in vacuo
6. customthe residue purified by reverse phase chromatography (0.05% TFA water/acetonitrile)