4-Methylmorpholine → 4-(2'-Methyl-6'-morpholin-4-ylmethyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophene-2-carboxamidine

Participants

Reaction Conditions

Reaction Steps

Methanesulfonyl chloride (100 μL) was added over 1 min to a 0° C. solution of {[4-(6′-hydroxymethyl-2′-methyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester (Example 5: step c) (30 mg)) and diisopropylethylamine (0.25 mL) in DCM (10 mL). The solution was stirred for 1 h at 0° C. and warmed to rt. 4-Methylmorpholine (0.5 mL) was added and the solution was stirred for 3 h at rt. The volatile components were removed in vacuo and the residue was treated with 1:1 TFA/DCM (10 mL) for 2 h at rt. The solvent was removed in vacuo and the residue was purified by preparative HPLC (C18-column, 10–70% CH3CN over 30 min) which yielded the title compound as a opaque glass (6.8 mg). 1H-NMR (CD3OD): δ 8.40 (s, 1H), 8.13 (ddd, 1H, J=1.2, 1.9, 7.9 Hz), 7.97 (t, 1H, J=1.6 Hz), 7.82 (t, 1H, J=7.9 Hz), 7.61 (m, 2H), 7.49 (m, 2H), 4.15 (d, 1H, J=13.5 Hz), 4.07 (d, 1H, J=13.5 Hz), 3.82 (br s, 4H), 2.75 (s, 3H), 2.18 (s, 2H), 2.03 (s, 3H), 1.31 (s, 2H). ESI-MS (m/z): Calcd. for C24H27N3O3S3 (M+H): 502.1; found: 502.1.

Provenance & Evidence