Reaction Steps
3-Bromomethylpyridine (0.30 mg, 1.2 mmol) was added to a suspension of vanillin (0.12 g, 0.79 mmol), potassium carbonate (0.33 g, 2.4 mmol) in acetone (5.0 mL) and treated according to Procedure 3. 3-Methoxy-4-(pyridin-3-ylmethoxy)benzaldehyde (88 mg, 46%) was obtained as a brown oil. Piperidine (36 μL, 0.36 mmol) was added to a suspension of 3-methoxy-4-(pyridin-3-ylmethoxy)benzaldehyde (0.88 mg, 0.36 mmol) and 2-[(carboxyacetyl)amino]benzoic acid (73 mg, 0.33 mmol) in toluene (5 mL) and treated according to Procedure 2, acidifying with 20% AcOH. (E)-2-[[3-(3-Methoxy-4-(pyridin-3-ylmethoxy)phenyl)-1-oxo-2-propenyl]amino]benzoic acid (58 mg, 44%) was obtained as a pure brown crystalline solid; mp 245-251° C.; δH (400 MHz, DMSO-d6) 3.84 (s, 3H, OCH3), 5.18 (s, 2H, OCH2), 6.80 (d, J=15.6 Hz, 1H, CH═CHCO), 7.12 (d, J5′,6′=8.0 Hz, 1H, H5′), 7.16 (t, J3,4=J4,5=8.0 Hz, 1H, H4), 7.24 (d, J5′,6′=8.0 Hz, 1H, H6′), 7.40-7.45 (m, 2H, H2′, Ar—H), 7.56 (d, J=15.6 Hz, 1H, CH═CHCO), 7.60 (t, J4,5=J5,6=8.0 Hz, 1H, H5), 7.87 (d, J=8.0 Hz, 1H, Ar—H), 8.00 (d, J3,4=8.0 Hz, 1H, H3), 8.55-8.67 (m, 3H, H6, Ar—H), 11.32 (s, 1H, NH); δC (100 MHz, DMSO-d6) 55.7, 67.6, 110.8, 113.4, 116.7, 120.2, 120.3, 122.4, 122.7, 123.6, 127.9, 131.1, 132.4, 133.9, 135.9, 141.0, 141.5, 149.1, 149.2, 149.3, 164.2, 169.5; HRMS (ESI) calculated for C23H20N2O5 [M+H]+ 404.1445 found 404.1445; vmax 758, 1257, 1509, 1586, 1671, 2931 cm−1.
