Triethylamine → tert-butyl N-[4-[3-[4-amino-2-methyl-6-(4-methylsulfonylbutanoylamino)phenyl]phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

Participants

Reaction Steps

The procedure in Example 261: step b was followed using 4-methanesulfonyl-butyryl chloride (Example 209: step a (53 mg, 0.29)), {[4-(6′-amino-2′-methyl-4′-nitro-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester ((Example 295: step h) 130 mg, 0.23 mmol), and Et3N (192 μL, 1.38 mmol) in DCM (5 mL). After stirring for 1 h, starting material remained and an additional 20 mg of acid chloride was added. The solution was partitioned between EtOAc (70 mL) and aq NH4Cl (30 mL) and the layers were separated. The organic layer was washed with NaHCO3 (20 mL) and brine (30 mL) and was dried over sodium sulfate. The solution was concentrated and the residue was purified by SiO2 flash column chromatography to yield 126 mg of the amide product. The residue dissolved in EtOH (5 mL). Saturated aqueous NH4Cl (1.5 mL) was added followed by iron powder (110 mg, 2 mmol). The mixture was vigorously stirred at 80° C. for 30 min. The solution was filtered through a 0.22 μm filter and was then partitioned between EtOAc (70 mL) and water (20 mL). The layers were separated, the organic solution was dried over sodium sulfate, and the solution was concentrated to give the crude title compound which was used without further purification. 1HMR (CDCl3): δ 7.99 (s, 1H), 7.96 (m, 2H), 7.77 (s, 1H), 7.57 (t, 1H, J=7.9 Hz), 7.43 (dt, 1H, J=1.3, 7.7 Hz), 7.10 (br s, 1H), 7.04 (br s, 1H), 6.43 (br s, 1H), 3.85 (br s, 2H), 2.92 (m, 2H), 2.88 (s, 3H), 2.56 (s, 3H), 2.20 (t, 2H, J=6.7 Hz), 1.98 (m, 2H), 1.90 (s, 3H), 1.50 (s, 9H).

Provenance & Evidence