Cl[S:2]([N:5]=[C:6]=[O:7])(=[O:4])=[O:3].Br[CH2:9][CH2:10][OH:11].C(N(CC)CC)C.Cl.[C:20]1([C@@H:26]2[CH2:28][C@H:27]2[NH2:29])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(Cl)Cl>[C:20]1([CH:26]2[CH2:28][CH:27]2[NH:29][S:2]([N:5]2[CH2:9][CH2:10][O:11][C:6]2=[O:7])(=[O:4])=[O:3])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
To a round bottom flask was added chlorosulfonyl isocyanate (0.4 mL, 4.64 mmol) and methylene chloride (5 mL) under an atmosphere of argon. The mixture was cooled in an ice bath and 2-bromoethanol (0.535 mL, 7.55 mmol) in methylene chloride (1 mL) was added dropwise. After stirring for 30 minutes at 0° C., triethylamine (2.28 mL, 16.4 mmol) and trans-2-phenylcyclopropylamine hydrochloride (0.867 g, 5.11 mmol), 6a, in methylene chloride (5 mL) was added at such a rate that the reaction temperature was maintained between 0° C. and 10° C. The resulting solution was stirred at rt for 5 h and then partitioned between 1N HCl and water. The organic layer was dried with sodium sulfate, filtered and concentrated. The crude was purified by chromatography to give 569 mg of a waxy solid, 8a. 1H NMR (300 MHz, DMSO-d6): δ 7.34-7.22 (m, 3H), 7.12 (d, J=7.0 Hz, 2H), 6.00 (s, 1H), 4.50-4.33 (m, 2H), 4.16-3.95 (m, 2H), 2.66-2.61 (m, 1H), 2.43-2.37 (m, 1H), 1.48-1.41 (m, 1H), 1.30 (q, J=6.5 Hz, 1H). MS m/z: 283 (M+1).
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