Reaction Steps
Piperidine (0.45 mL, 4.6 mmol) was added to a suspension of 3-methoxy-4-(pent-1-ynyloxy)benzaldehyde (1.0 g, 4.6 mmol) and 2-[(carboxyacetyl)amino]benzoic acid (0.93 g, 4.2 mmol) in toluene (10 mL) and treated according to Procedure 2, acidifying with 1 M HCl. The crude product was recrystallised from EtOH/water providing (E)-2-[[3-(3-methoxy-4-(pent-4-ynyloxy)phenyl)-1-oxo-2-propenyl]amino]benzoic acid (1.2 g, 75%) as a pale yellow crystalline solid; mp 166.5-167.5° C.; δH (400 MHz, DMSO-d6) 1.89 (p, J=7.6 Hz, 2H, CH2), 2.32 (dt, J=7.6, 2.4 Hz, 2H, CH2CCH), 2.81 (t, J=2.4 Hz, 1H, CCH), 3.84 (s, 3H, OCH3), 4.06 (t, J=7.6 Hz, 2H, OCH2), 6.78 (d, J=15.6 Hz, 1H, CH═CHCO), 6.99 (d, J5′,6′=8.0 Hz, 1H, H5′), 7.17 (t, J3,4=J4,5=8.0 Hz, 1H, H4), 7.22 (dd, J5′,6′=8.0, J2′,6′=2.0 Hz, 1H, H6′), 7.37 (d, J2′,6′=2.0 Hz, 1H, H2′), 7.55 (d, J=15.6 Hz, 1H, CH═CHCO), 7.60 (t, J4,5=J5,6=8.0 Hz, 1H, H5), 8.00 (d, J3,4=8.0 Hz, 1H, H3), 8.62 (d, J5,6=8.0 Hz, 1H, H6), 11.27 (s, 1H, NH), 13.56 (br s, 1H, CO2H); δC (100 MHz, DMSO-d6) 14.5, 27.7, 55.7, 66.7, 71.7, 83.6, 110.7, 112.7, 116.6, 120.0, 120.3, 122.6, 122.7, 127.4, 131.1, 134.0, 141.1, 141.6, 149.2, 149.8, 164.1, 169.4; HRMS (ESI) calculated for C22H21NO5 [M+H]+ 380.1492. found 380.1493; vmax 755, 1257, 1506, 1584, 1657, 2929, 3266, 3519 cm−1.
