[5-(2-Amino-phenyl)-thiophen-2-yl]-acetic acid methyl ester → (5-{2-[(3',4',5'-Trimethoxy-biphenyl-2-carbonyl)-amino]-phenyl}-thiophen-2-yl)-acetic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

Add a solution of 3′,4′,5′-Trimethoxy-biphenyl-2-carbonyl chloride (57) (0.18 mmol) in DCM (1.0 mL) to an ice cooled solution of [5-(2-Amino-phenyl)-thiophen-2-yl]-acetic acid methyl ester (36) (46 mg, 0.18 mmol) in anhydrous DCM (2.0 mL) and anhydrous pyridine (0.5 mL). Stir the reaction mixture for 1 h at 0° C. and additional 20 h at rt. Pour the reaction mixture into ice cooled 1M aqu. HCl, extract with EtOAc (2×) and DCM (2×), wash the combined organic layer with brine and dry with Na2SO4. Purify the crude product by preparative radial chromatography (silica gel, EtOAc/CyH 1+2) to obtain (5-{2-[(3′,4′,5′-Trimethoxy-biphenyl-2-carbonyl)-amino]-phenyl}-thiophen-2-yl)-acetic acid methyl ester (58) as a light brown solid (58 mg, 59%). 1H NMR (400 MHz, CDCl3): 3.70 (s, 3H); 3.76 (s, 6H); 3.78 (s, 2H); 3.80 (s, 3H); 6.29 (d, 1H, J=3.4 Hz); 6.60 (s, 2H); 6.75 (d, 1H, J=3.4 Hz); 7.07 (t, 1H, J=7.6 Hz); 7.23 (d, 1H, J=7.6 Hz); 7.31 (t, 1H, J=8.0 Hz); 7.37-7.43 (m, 2H); 7.48 (t, 1H, J=7.6 Hz); 7.52 (s, 1H); 7.69 (d, 1H, J=8.0 Hz); 8.45 (d, 1H, J=8.0 Hz).

Provenance & Evidence