Reaction Steps
Sodium ascorbate (5.4 mg, 27 μmol), tris-(benzyltriazolylmethyl)amine (2.9 mg, 5.5 μmol) and copper sulfate (0.88 mg, 5.5 μmol) were added to a solution of (E)-2-[[3-(3,4-dimethoxyphenyl)-1-oxo-2-propenyl]amino]-N-(prop-2-ynyl)benzamide (100 mg, 0.27 mmol) and 2-azido-N-phenylacetamide (48 mg, 0.27 mmol) in DMSO (4.0 mL) and water (1.0 mL). The solution was stirred at rt for 16 h and diluted with water. The suspension was filtered and the filter cake was washed with water and dried. The product was recrystallised from acetonitrile and (E)-2-(3-(3,4-dimethoxyphenyl)acrylamido)-N-((1-(2-oxo-2-(phenylamino)ethyl)-1H-1,2,3-triazol-4-yl)methyl)benzamide (127 mg, 86%) was obtained as a colourless solid; mp 189-191° C.; δH (400 MHz, DMSO-d6) 3.77 (s, 3H, OCH3), 3.81 (s, 3H, OCH3), 4.59 (d, J=6.8 Hz, 2H, CH2NH), 5.30 (s, 2H, CH2N), 6.79 (d, J=15.6 Hz, 1H, CH═CHCO), 6.96 (d, J5′,6′=8.4 Hz, 1H, H5′), 7.06 (t, J3″,4″=J4″,5″=8.0 Hz, 1H, H4″), 7.15 (t, J3,4=J4,5=8.4 Hz, 1H, H4), 7.23 (dd, J5′,6′=8.4, J2′,6′=1.6 Hz, 1H, H6′), 7.28 (t, J2″,3″=J3″,4″=J4″,5″=J5″,6″=8.0 Hz, 2H, H3″, H5″), 7.37 (d, J2′,6′=1.6 Hz, 1H, H2′), 7.50-7.56 (m, 4H, CH═CHCO, H5, H2″, H6″), 7.78 (d, J3,4=8.0 Hz, 1H, H3), 8.08 (s, 1H, C═CH), 8.57 (d, J5,6=8.0 Hz, 1H, H6), 9.37 (t, J=5.6 Hz, 1H, CH2NH), 10.43 (s, 1H, NHPh), 11.40 (s, 1H, NH); δC (100 MHz, DMSO-d6) 34.9, 40.4, 52.2, 55.5, 55.6, 110.4, 111.5, 119.2, 119.9, 120.7, 120.8, 122.6, 122.7, 123.7, 124.6, 127.3, 128.1, 128.9, 131.9, 138.4, 139.2, 141.5, 144.5, 148.9, 150.6, 164.0, 164.2, 168.3; HRMS (ESI) calculated for C29H28N6O5 [M+Na]+ 563.2013. found 516.2015; vmax 755, 1023, 1259, 1516, 1671, 3262 cm−1.
