Water → 4-[5-[[3-methyl-2-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]-5-(2-trimethylsilylethoxycarbonylamino)phenyl]carbamoylamino]pentoxy]benzoic acid

Participants

Reaction Steps

Lithium hydroxide (45.8 mg, 2.08 mmol) was added to a solution of 4-(5-{3-[3′-[5-(tert-butoxycarbonylamino-imino-methyl)-2-methylsulfanyl-thiophene-3-sulfonyl]-6-methyl-4-(2-trimethylsilanyl-ethoxycarbonylamino)-biphenyl-2-yl]-ureido}-pentyloxy)-benzoic acid methyl ester (280 mg, 0.298 mmol, Example 283: step c) in 1,4-dioxane:water (10 mL, 2:1) over 2 days at rt. The solvents were removed in vacuo. The residue was diluted in water, acidified to pH˜5 with acetic acid, and extracted with EtOAc. The organic layer was washed with brine and dried over magnesium sulfate. The solvents were removed in vacuo to afford the title compound as a yellow solid (276 mg, quantitative). 1H-NMR (CDCl3/CD3OD): δ 7.93–7.99 (m, 3H), 7.83–7.86 (m, 2H), 7.52–7.59 (m, 2H), 7.15–7.20 (m, 2H), 6.85–6.89 (m, 2H), 4.21–4.26 (m, 2H), 3.99 (t, 2H, J=6.43 Hz), 3.13–3.24 (m, 2H), 2.61 (s, 3H), 2.02 (s, 3H), 1.75–1.83 (m, 2H), 1.43–1.56 (m, 13H), 1.02–1.08 (m, 2H), 0.07 (s, 9H).

Provenance & Evidence