The perfect solution is was cooled to ?40 C, and triphosgene (1.61 g, 5.52 mmol) was added portionwise. (specifically, 7-halo) 4-AQs had been shown to screen enhanced actions against extremely resistant strains of cyclization. This cyclization for an aza-aurone part product probably makes up about the diminished produces, since it will not require exterior acidity activation and may take place through the reaction therefore. Additionally, it’s possible that withdrawing electron denseness through substituent results makes ynimines 8 even more vunerable to hydrolysis through the cyclization stage. Gratifyingly, the created conditions demonstrated to tolerate aliphatic alkynes, aswell, as demonstrated from the isolation of 9n and 9o, with somewhat lower yield for 9n as a complete consequence of the volatility of 1-hexyne. Open in another window Structure 4 Alkyne and = 0.19 (cHex/EtOAc/Et3N 4:1:0.05); mp 139 C; 1H NMR (500.23 MHz, CDCl3) 8.10C8.03 (m, 3H), 7.68 (dd, = 1.5, 8.5 Hz, 1H), 7.63 (ddd, = 1.5, 7.0, 8.5 Hz, 1H), 7.51 (t, = 7.5 Hz, 2H), 7.47C7.38 (m, 2H), 7.12 (s, 1H), 5.03 (bs, 1H), 1.60 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 157.9, 148.8, 148.3, 141.2, 130.5, 129.0, 128.8, 128.6, 127.5, 124.3, 118.9, 118.5, 99.1, 51.5, 29.4; HRMS (ESI) calcd for C19H21N2+ [M + H]+ 277.1695, found 277.1707. = 0.33 (cHex/EtOAc/Et3N 4:1:0.05); mp 134 C; 1H NMR (500.23 MHz, CDCl3) 8.05 (dd, = 1.5, 7.5 Hz, 2H), 7.85 (s, 1H), 7.57 (d, = 8.5 Hz, 1H), 7.50 (t, = 7.5 Hz, 2H), 7.47C7.40 (m, 1H), 7.23 (dd, = 7.5, 8.5 Hz, 1H), 7.07 (d, = 1.5 Hz, 1H), 4.99 (bs, 1H), 2.52 (s, 3H), 1.59 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 157.9, 149.0, 148.3, 141.3, 139.0, 129.7, 128.7, 128.6, 127.5, 126.4, 118.6, 116.4, 98.7, 51.4, 29.4, 21.5; HRMS (ESI) calcd for C20H23N2+ [M + H]+ 291.1851, found 291.1854. = 0.44 (cHex/EtOAc/Et3N 4:1:0.05); mp 163 LG-100064 C; 1H NMR (500.23 MHz, CDCl3) 8.14C8.06 (m, 3H), 7.54 (t, = 7.5 Hz, 2H), 7.50C7.44 (m, 1H), 7.48C7.37 (m, 1H), 7.36 (dd, = 2.5, 10.0 Hz, 1H), 7.17 (s, 1H), 4.79 (bs, 1H), 1.57 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 159.5 (d, = 245.0 Hz), 157.3 (d, = 2.5 Hz), 147.9 (d, = 4.5 Hz), 145.8, 140.9, 132.8 (d, = 8.5 Hz), 128.8, 128.6, 127.4, 118.9 (d, = 8.0 Hz), 118.6 (d, = 24.5 Hz), 103.3 (d, = 23.0 Hz), 99.4, 51.6, 29.3; HRMS (ESI) calcd for C19H20N2F+ [M + H]+ 295.1601, Rabbit Polyclonal to SHP-1 (phospho-Tyr564) found 295.1604. = 0.43 (cHex/EtOAc/Et3N 4:1:0.05); mp 155 C; 1H NMR (500.23 MHz, CDCl3) 8.04 (dd, = 5.5, 9.0 Hz, 1H), 7.95 (d, = 8.0 Hz, 2H), 7.42C7.36 (m, 1H), 7.34C7.27 (m, 3H), 7.12 (s, 1H), 4.74 (bs, 1H), 2.43 (s, 3H), 1.59 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 159.5 (d, = 245.0 Hz), 157.3 (d, = 2.5 Hz), 147.8 (d, = 5.0 Hz), 145.8, 138.8, 138.0, 132.7 (d, = 8.5 Hz), 129.4, 127.3, 118.9 (d, = 8.0 Hz), 118.5 (d, = 25.0 Hz), 103.3 (d, = 23.0 Hz), 99.3, 51.5, 29.3, 21.3; HRMS (ESI) calcd for C20H22N2F+ [M + H]+ 309.1757, found 309.1769. = 0.69 (cHex/EtOAc/Et3N 4:1:0.01); mp 166C167 C; 1H NMR (500.23 MHz, CDCl3) 7.98 (dd, = 8.0, 2.0 Hz, 1H), 7.42 (s, 1H), 7.34C7.28 (m, 3H), 7.17 (s, 1H), 4.86 (s, 0H), 2.42 (s, 3H), 1.59 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 159.8, 157.8 (d, = 18.5 Hz), 147.3 (d, = 3.5 Hz), 138.4 (d, = 235.5 Hz), 138.2 (d, = 11.0 Hz), 129.4, 128.5 (d, = 11.0 Hz), 127.37, 120.6 (d, = 3.5 Hz), 114.7 (d, = 23.0 Hz), 114.4 (d, = 4.5 Hz), 100.1, 51.8, 29.3, 21.4; HRMS (ESI) calcd for C20H21N2ClF+ [M + H]+ 343.1368, found 343.1376. = 0.58 (cHex/EtOAc/Et3N 4:1:0.01); mp 51C54 C; 1H NMR (500.23 MHz, CDCl3) 8.08C7.98 (m, 2H), 7.89 (d, = 6.5 Hz, 1H), 7.59 (d, = 9.0 Hz, 1H), 7.47C7.39 LG-100064 (m, 2H), 7.34 (d, = 9.0 Hz, 1H), 7.04 (s, 1H), 5.03 (bs, 1H), 1.59 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 157.3, 149.5, 148.6, 142.5, 135.0, 134.7, 129.9, 129.3, 129.0, 127.6, 125.5, 125.2, 120.5, 117.0, 98.9, 51.7, 29.3; HRMS (ESI) calcd for C19H19N2Cl2+ [M + H]+ 345.0917, found 345.0925. = 0.33 (cHex/EtOAc/Et3N 4:1:0.05); mp 138 C; 1H NMR (500.23 MHz, CDCl3) 8.09C8.01 (m, 3H), 7.68 (d, = 8.5 Hz, 1H), 7.67C7.60 (m, 1H), 7.44C7.37 (m, 1H), 7.19 (t, = 8.5 Hz,.Gratifyingly, the developed conditions demonstrated to tolerate aliphatic alkynes, aswell, as proven by the isolation of 9n and 9o, with somewhat lower produce for 9n due to the volatility of 1-hexyne. Open in another window Scheme 4 Alkyne and = 0.19 (cHex/EtOAc/Et3N 4:1:0.05); mp 139 C; 1H NMR (500.23 MHz, CDCl3) 8.10C8.03 (m, 3H), 7.68 (dd, = 1.5, 8.5 Hz, 1H), 7.63 (ddd, = 1.5, 7.0, 8.5 Hz, 1H), 7.51 (t, = 7.5 Hz, 2H), 7.47C7.38 (m, 2H), 7.12 (s, 1H), 5.03 (bs, 1H), 1.60 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 157.9, 148.8, 148.3, 141.2, 130.5, 129.0, 128.8, 128.6, 127.5, 124.3, 118.9, 118.5, 99.1, 51.5, 29.4; HRMS (ESI) calcd for C19H21N2+ [M + H]+ 277.1695, found 277.1707. = 0.33 (cHex/EtOAc/Et3N 4:1:0.05); mp 134 C; 1H NMR (500.23 MHz, CDCl3) 8.05 (dd, = 1.5, 7.5 Hz, 2H), 7.85 (s, 1H), 7.57 (d, = 8.5 Hz, 1H), 7.50 (t, = 7.5 Hz, 2H), 7.47C7.40 (m, 1H), 7.23 (dd, LG-100064 = 7.5, 8.5 Hz, 1H), 7.07 (d, = 1.5 Hz, 1H), 4.99 (bs, 1H), 2.52 (s, 3H), 1.59 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 157.9, 149.0, 148.3, 141.3, 139.0, 129.7, 128.7, 128.6, 127.5, 126.4, 118.6, 116.4, 98.7, 51.4, 29.4, 21.5; HRMS (ESI) calcd for C20H23N2+ [M + H]+ 291.1851, found out 291.1854. = 0.44 (cHex/EtOAc/Et3N 4:1:0.05); mp 163 C; 1H NMR (500.23 MHz, CDCl3) 8.14C8.06 (m, 3H), 7.54 (t, = 7.5 Hz, 2H), 7.50C7.44 (m, 1H), 7.48C7.37 (m, 1H), 7.36 (dd, = 2.5, 10.0 Hz, 1H), 7.17 (s, 1H), 4.79 (bs, 1H), 1.57 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 159.5 (d, = 245.0 Hz), 157.3 (d, = 2.5 Hz), 147.9 (d, = 4.5 Hz), 145.8, 140.9, 132.8 (d, = 8.5 Hz), 128.8, 128.6, 127.4, 118.9 (d, = 8.0 Hz), 118.6 (d, = 24.5 Hz), 103.3 (d, = 23.0 Hz), 99.4, 51.6, 29.3; HRMS (ESI) calcd for C19H20N2F+ [M + H]+ 295.1601, found out 295.1604. = 0.43 (cHex/EtOAc/Et3N 4:1:0.05); mp 155 C; 1H NMR (500.23 MHz, CDCl3) 8.04 (dd, = 5.5, 9.0 Hz, 1H), 7.95 (d, = 8.0 Hz, 2H), 7.42C7.36 (m, 1H), 7.34C7.27 (m, 3H), 7.12 (s, 1H), 4.74 (bs, 1H), 2.43 (s, 3H), 1.59 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 159.5 (d, = 245.0 Hz), 157.3 (d, = 2.5 Hz), 147.8 (d, = 5.0 Hz), 145.8, 138.8, 138.0, 132.7 (d, = 8.5 Hz), 129.4, 127.3, 118.9 (d, = 8.0 Hz), 118.5 (d, = 25.0 Hz), 103.3 (d, = 23.0 Hz), 99.3, 51.5, 29.3, 21.3; HRMS (ESI) calcd for C20H22N2F+ [M + H]+ 309.1757, found 309.1769. = 0.69 (cHex/EtOAc/Et3N 4:1:0.01); mp 166C167 C; 1H NMR (500.23 MHz, CDCl3) 7.98 (dd, = 8.0, 2.0 Hz, 1H), 7.42 (s, 1H), 7.34C7.28 (m, 3H), 7.17 (s, 1H), 4.86 (s, 0H), 2.42 (s, 3H), 1.59 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 159.8, 157.8 (d, = 18.5 Hz), 147.3 (d, = 3.5 Hz), 138.4 (d, = 235.5 Hz), 138.2 (d, = 11.0 Hz), 129.4, 128.5 (d, = 11.0 Hz), 127.37, 120.6 (d, = 3.5 Hz), 114.7 (d, = 23.0 Hz), 114.4 (d, = 4.5 Hz), 100.1, 51.8, 29.3, 21.4; HRMS (ESI) calcd for C20H21N2ClF+ [M + H]+ 343.1368, found 343.1376. = 0.58 (cHex/EtOAc/Et3N 4:1:0.01); mp 51C54 C; 1H NMR (500.23 MHz, CDCl3) 8.08C7.98 (m, 2H), 7.89 (d, = 6.5 Hz, 1H), 7.59 (d, = 9.0 Hz, 1H), 7.47C7.39 (m, 2H), 7.34 (d, = 9.0 Hz, 1H), 7.04 (s, 1H), 5.03 (bs, 1H), 1.59 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 157.3, 149.5, 148.6, 142.5, 135.0, 134.7, 129.9, 129.3, 129.0, 127.6, 125.5, 125.2, 120.5, 117.0, 98.9, 51.7, 29.3; HRMS (ESI) calcd for C19H19N2Cl2+ [M + H]+ 345.0917, found 345.0925. = 0.33 (cHex/EtOAc/Et3N 4:1:0.05); mp 138 C; 1H NMR (500.23 MHz, CDCl3) 8.09C8.01 (m, 3H), 7.68 (d, = 8.5 Hz, 1H), 7.67C7.60 (m, 1H), 7.44C7.37 (m, 1H), 7.19 (t, = 8.5 Hz, 2H), 7.06 (s, 1H), 5.05 (bs, 1H), 1.60 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 163.4 (d, = 248.0 Hz), 156.8, 148.8, 148.4, 137.3 (d, = 3.0 Hz), 130.4, 129.2 (d, = 8.5 Hz), 129.1, 124.4, 118.9, 118.4, 115.5 (d, = 21.5 Hz), 98.7; HRMS (ESI) calcd for C19H20N2F+ [M + H]+ 295.1601, found out 295.1601. = 0.38 (cHex/EtOAc/Et3N 4:1:0.01); mp 47C49 C; 1H NMR (500.23 MHz, CDCl3) 8.11C7.99 (m, 2H), 7.78C7.57 (m, 2H), 7.13 (t, = 8.5 Hz, 1H), 7.08C6.93 (m, 3H), 4.97 (bs, 1H), 3.88 (s, 3H), 1.59 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 163.0 (d, = 248.0 Hz), 160.5, 158.5, 150.3 (d, = 12 Hz), 148.4, 133.3, 128.8, 121.1 (d, = 10.0 Hz), 114.0, 113.7 (d, = 19.5 Hz), 113.6 (d, = 25.0 Hz), 98.3, 55.4, 51.6, 29.4); HRMS (ESI) calcd for C20H22N2FO+ [M + H]+ 325.1706, found 325.1723. = 0.29 (cHex/EtOAc/Et3N 4:1:0.01); mp 56C61 C; 1H NMR (500.23 MHz, CDCl3) 8.06 (m, 2H), 7.57 (d, = 9.0 Hz, 1H), 7.54C7.47 (m, 2H), 7.46C7.41 (m, 2H), 7.04 (dd, = 2.5, 9.0 Hz, 1H), 7.02 s, 1H), 4.96 (bs, 1H), 3.94 (s, 3H), 1.58 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 160.2, 158.4, 150.7, 148.5, 141.3, 128.7, 128.6, 127.4, 120.2, 116.7, 112.9, 108.6, 98.2, 55.4, 51.5, 29.4; HRMS (ESI) calcd for C20H23N2O+ [M + H]+ 307.1800, found 307.1788. = 0.10 (cHex/EtOAc/Et3N 4:1:0.01); mp 67C69 C; 1H NMR (500.23 MHz, CDCl3) 8.06 (d, = 8.5 Hz, 1H), 7.68 (d, = 8.5 Hz, 1H), 7.63 (t, = 7.5 Hz, 1H), 7.40 (t, = 7.5 Hz, 1H), 7.26 (s, 2H), 7.03 (s, 1H), 5.06 (bs, 1H), 3.99 (s, 6H), 3.90 (s, 3H), 1.59 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 157.8, 153.3, 184.6, 148.6, 148.4, 138.9, 130.3, 129.1, 124.4, 118.9, 118.4, 104.9, 99.1, 60.3, 56.2, 51.5, 29.4; HRMS (ESI) calcd for C22H27N2O3+ [M + H]+ 367.2010, found 367.2026. = 0.28 (cHex/EtOAc/Et3N 4:1:0.01); mp 68C70 C; 1H NMR (500.23 MHz, CDCl3) 8.03 (s, 1H), 7.60 (dd, = 2.0, 9.0 Hz, 1H), 7.33 (dt, = 2.0, 9.0 Hz, 1H), 7.25 (d, = 1.5 Hz, 2H), 7.02 (d, = 1.5 Hz, 1H), 5.00 (bs, 1H), 3.98 (s, 6H), 3.91 (s, 3H), 1.59 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 158.7, 153.3, 149.5, 148.4, 139.1, 136.6, 134.9, 129.2, 124.9, 120.5, 116.9, 104.8, 99.2, 60.9, 56.3, 51.7, 29.3; HRMS (ESI) calcd for C22H26N2O3Cl+ [M + H]+ 401.1621, found 401.1634. Methyl 4-(= 0.38 (cHex/EtOAc/Et3N 4:1:0.01); mp 131C134 C; 1H NMR (500.23 MHz, CDCl3) 8.49 (s, 1H), 8.19 (dd, = 2.0, 8.5 Hz, 1H), 8.11C8.02 (m, 3H), 7.56C7.49 (m, 2H), 7.49C7.45 (m, 1H), 7.15 (s, 1H), 5.27 (bs, 1H), 3.99 (s, 3H), 1.62 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 167.0, 159.8, 151.3, 149.4, 140.7, 130.5, 129.3, 128.7, 128.6, 127.6, 125.2, 122.5, 117.7, 99.5, 52.3, 51.9, 29.3; HRMS (ESI) calcd for C21H23N2O2+ [M + H]+ 335.1749, found 335.1759. 4-(4-(= 0.33 (cHex/EtOAc/Et3N 4:1:0.01); mp 79C81 C; 1H NMR (500.23 MHz, CDCl3) 8.18 (d, = 8.5 Hz, 2H), 8.04 (dd, = 1.5, 8.5 Hz, 1H), 7.79 (d, = 8.5 Hz, 2H), 7.70 (dd, = 1.5, 8.5 Hz, 1H), 7.66 (ddd, = 1.5, 7.0, 8.5 Hz, 1H), 7.45 (ddd, = 1.5, 7.0, 8.5 Hz, 1H), 7.09 (s, 1H), 5.13 (bs, 1H), 1.61 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 155.6, 148.7, 145.4, 132.5, 130.6, 129.4, 128.1, 125.1, 119.0, 118.9, 118.6, 112.2, 98.7, 51.7, 29.3; HRMS (ESI) calcd for C20H20N3+ [M + H]+ 302.1648, found 302.1656. = 0.53 (EtOAc/Et3N 100:1); mp 68C70 C; 1H NMR (500.23 MHz, CDCl3) 7.91 (d, = 8.5 Hz, 1H), 7.62 (d, = 8.5 Hz, 1H), 7.59C7.53 (m, 1H), 7.35 (ddd, = 1.0, 7.0, 8.5 Hz, 1H), 6.57 (s, 1H), 4.91 (bs, 1H), 2.87C2.79 (m, 2H), 1.81C1.72 (m, 2H), 1.54 (s, 9H), 1.51C1.40 (m, 2H), 0.96 (t, = 7.5 Hz, 3H); 13C NMR (125.97 MHz, CDCl3) 163.0, 148.4, 147.8, 129.5, 128.7, 123.7, 118.8, 118.1, 100.8, 51.4, 39.6, 32.4, 29.3, 22.7, 14.1; HRMS (ESI) calcd for C17H25N2+ [M + H]+ 257.2007, found out 257.2023. = 0.62 (EtOAc:Et3N 100:1); 1H NMR (500.23 MHz, CDCl3) 7.92 (d, = 8.5 Hz, 1H), 7.62 (d, = 8.5 Hz, 1H), 7.56 (ddd, = 1.5, 7.0, 8.5 Hz, 1H), 7.34 (t, = 1.5, 7.5, 7.0 Hz, 1H), 6.57 (s, 1H), 4.91 (bs, 1H), 2.82 (t, = 8.0 Hz, 2H), 1.78 (p, = 8.0 Hz, 2H), 1.53 (s, 9H), 1.46C1.38 (m, 2H), 1.38C1.32 (m, 2H), 1.31C1.21 (m, 10H), 0.87 (t, = 7.0 Hz, 3H); 13C NMR (125.97 MHz, CDCl3) 163.0, 148.4, 147.8, 129.5, 128.6, 123.7, 118.8, 118.1, 100.8, 51.3, 39.9, 31.9, 30.2, 29.62, 29.58, 29.56, 29.3, 29.2, 22.6, 14.1; HRMS (ESI) calcd for C23H37N2+ [M + H]+ 341.2943, found 341.2965. = 0.16 (cHex/EtOAc/Et3N 4:1:0.05); mp 176 C; 1H NMR (500.23 MHz, CDCl3) 8.12 (m, 3H), 7.72 (d, = 8.5 Hz, 1H), 7.68C7.61 (m, 1H), 7.51 (t, = 7.5 Hz, 2H), 7.48C7.38 (m, 2H), 6.89 (s, 1H), 4.87 (bd, = 7.0 Hz, 1H), 4.04C3.92 (m, 1H), 1.40 (dd, = 1.5, 6.5 Hz, 6H); 13C NMR (125.97 MHz, CDCl3) 158.4, 149.0, 148.7, 141.1, 130.3, 129.1, 128.7, 128.5, 127.5, 124.2, 119.0, 117.8, 97.0, 43.9, 22.5; HRMS (ESI) calcd for C18H19N2+ [M + H]+ 263.1539, found 263.1556. = 0.50 (cHex/EtOAc/Et3N 4:1:0.01); mp 146C149 C; 1H NMR (500.23 MHz, CDCl3) 8.09C8.06 (m, 1H), 8.04 (d, = 8.0 Hz, 2H), 7.51 (d, = 7.0 Hz, 2H), 7.47C7.37 (m, 2H), 7.34 (dd, = 2.0, 10.0 Hz, 1H), 6.86 (s, 1H), 4.71 (bd, = 7.5 Hz, 1H), 3.66C3.56 (m, 1H), 2.20 (dd, = 4.0, 13.0 Hz, 2H), 1.89C1.81 (m, 2H), 1.76C1.70 (m, 1H), 1.53C1.44 (m, 2H), 1.42C1.30 (m, 3H); 13C NMR (125.97 MHz, CDCl3) 159.5 (d, = 245.0), 157.9 (d, = 2.5 Hz), 148.6 (d, = 5.0 Hz), 145.7, 140.8, 132.5 (d, = 8.5 Hz), 128.9, 128.6, 127.5, 118.8 (d, = 25.0 Hz), 118.2 (d, = 8.0 Hz), 103.4 (d, = 23.0 Hz), 97.3, 51.3, 32.8, 25.7, 24.8; HRMS (ESI) calcd for C21H22N2F+ [M + H]+ 321.1757, found 321.1776. 7-Chloro-= 0.47 (cHex/EtOAc/Et3N 4:1:0.01); mp 147C148 C; 1H NMR (500.23 MHz, CDCl3) 8.11C8.00 (m, 3H), 7.65 (d, = 9.0 Hz, 1H), 7.53C7.48 (m, 2H), 7.47C7.43 (m, 1H), 7.34 (dd, = 2.0, 9.0 Hz, 1H), 6.85 (s, 1H), 4.88 (bs, 1H), 4.04C3.91 (m, 1H), 1.40 (d, = 6.5 Hz, 6H); 13C NMR (125.97 MHz, CDCl3) 159.3, 149.4, 149.2, 140.5, 135.0, 129.1, 129.0, 128.6, 127.5, 124.9, 120.6, 116.2, 97.2, 44.1, 22.5; HRMS (ESI) calcd for C18H18N2Cl+ [M + H]+ 297.1150, found 297.1163. = 0.35 (cHex/EtOAC/Et3N 4:1:0.01); 1H NMR (500.23 MHz, CDCl3) 8.14C8.06 (m, 3H), 7.72 (d, = 8.5 Hz, 1H), 7.65 (t, = 7.5 Hz, 1H), 7.51 (t, = 7.5 Hz, 2H), 7.47C7.38 (m, 2H), 6.86 (s, 1H), 5.00 (bt, = 5.0 Hz, 1H), 3.36 (q, = 6.5 Hz, 2H), 1.79 (p, = 7.5 Hz, 2H), 1.53C1.37 (m, 4H), 0.96 (t, = 7.0 Hz, 3H); 13C NMR (125.97 MHz, CDCl3) 158.4, 150.1, 148.6, 141.0, 130.2, 129.1, 128.8, 128.5, 127.5, 124.3, 119.0, 117.8, 96.6, 43.2, 29.3 28.6, 22.4, 14.0; HRMS (ESI) calcd for C20H23N2+ [M + H]+ 291.1851, found out 291.1846. = 0.39 (cHex/EtOAc/Et3N 4:1:0.01); mp 60C63 C; 1H NMR (500.23 MHz, CDCl3) 8.18 (d, = 8.0 Hz, 2H), 8.07 (d, = 8.5 Hz, 1H), 7.79C7.70 (m, 3H), 7.67 (t, = 7.5 Hz, 1H), 7.44 (t, = 7.5 Hz, 1H), 6.86 (s, 1H), 4.93 (bd, = 7.0 Hz, 1H), 4.05C3.96 (m, 1H), 1.41 (d, = 6.5 Hz, 6H); 13C NMR (125.97 MHz, CDCl3) 156.8, 149.3, 148.7, 144.4, 130.6 (q, = 32.5 Hz), 130.4, 129.4, 127.8, 125.5 (q, = 4.0 Hz), 124.8, 124.3 (q, = 271.5 Hz), 119.0, 117.9, 96.8, 40.0, 22.5; HRMS (ESI) calcd for C19H18N2F3+ [M + H]+ 331.1413, found 331.1429. Methyl 4-(Cyclohexylamino)-2-(3,4,5-trimethoxyphenyl)quinoline-6-carboxylate (9u) Synthesized relative to general procedure 2. response. Additionally, it’s possible that withdrawing electron denseness through substituent results makes ynimines 8 even more vunerable to hydrolysis through the cyclization stage. Gratifyingly, the created conditions demonstrated to tolerate aliphatic alkynes, aswell, as demonstrated from the isolation of 9n and 9o, with relatively lower produce for 9n due to the volatility of 1-hexyne. Open up in another window Structure 4 Alkyne and = 0.19 (cHex/EtOAc/Et3N 4:1:0.05); mp 139 C; 1H NMR (500.23 MHz, CDCl3) 8.10C8.03 (m, 3H), 7.68 (dd, = 1.5, 8.5 Hz, 1H), 7.63 (ddd, = 1.5, 7.0, 8.5 Hz, 1H), 7.51 (t, = 7.5 Hz, 2H), 7.47C7.38 (m, 2H), 7.12 (s, 1H), 5.03 (bs, 1H), 1.60 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 157.9, 148.8, 148.3, 141.2, 130.5, 129.0, 128.8, 128.6, 127.5, 124.3, 118.9, 118.5, 99.1, 51.5, 29.4; HRMS (ESI) calcd for C19H21N2+ [M + H]+ 277.1695, found 277.1707. = 0.33 (cHex/EtOAc/Et3N 4:1:0.05); mp 134 C; 1H NMR (500.23 MHz, CDCl3) 8.05 (dd, = 1.5, 7.5 Hz, 2H), 7.85 (s, 1H), 7.57 (d, = 8.5 Hz, 1H), 7.50 (t, = 7.5 Hz, 2H), 7.47C7.40 (m, 1H), 7.23 (dd, = 7.5, 8.5 Hz, 1H), 7.07 (d, = 1.5 Hz, 1H), 4.99 (bs, 1H), 2.52 (s, 3H), 1.59 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 157.9, 149.0, 148.3, 141.3, 139.0, 129.7, 128.7, 128.6, 127.5, 126.4, 118.6, 116.4, 98.7, 51.4, 29.4, 21.5; HRMS (ESI) calcd for C20H23N2+ [M + H]+ 291.1851, found 291.1854. = 0.44 (cHex/EtOAc/Et3N 4:1:0.05); mp 163 C; 1H NMR (500.23 MHz, CDCl3) 8.14C8.06 (m, 3H), 7.54 (t, = 7.5 Hz, 2H), 7.50C7.44 (m, 1H), 7.48C7.37 (m, 1H), 7.36 (dd, = 2.5, 10.0 Hz, 1H), 7.17 (s, 1H), 4.79 (bs, 1H), 1.57 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 159.5 (d, = 245.0 Hz), 157.3 (d, = 2.5 Hz), 147.9 (d, = 4.5 Hz), 145.8, 140.9, 132.8 (d, = 8.5 Hz), 128.8, 128.6, 127.4, 118.9 (d, = 8.0 Hz), 118.6 (d, = 24.5 Hz), 103.3 (d, = 23.0 Hz), 99.4, 51.6, 29.3; HRMS (ESI) calcd for C19H20N2F+ [M + H]+ 295.1601, found 295.1604. = 0.43 (cHex/EtOAc/Et3N 4:1:0.05); mp 155 C; 1H NMR (500.23 MHz, CDCl3) 8.04 (dd, = 5.5, 9.0 Hz, 1H), 7.95 (d, = 8.0 Hz, 2H), 7.42C7.36 (m, 1H), 7.34C7.27 (m, 3H), 7.12 (s, 1H), 4.74 (bs, 1H), 2.43 (s, 3H), 1.59 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 159.5 (d, = 245.0 Hz), 157.3 (d, = 2.5 Hz), 147.8 (d, = 5.0 Hz), 145.8, 138.8, 138.0, 132.7 (d, = 8.5 Hz), 129.4, 127.3, 118.9 (d, = 8.0 Hz), 118.5 (d, = 25.0 Hz), 103.3 (d, = 23.0 Hz), 99.3, 51.5, 29.3, 21.3; HRMS (ESI) calcd for C20H22N2F+ [M + H]+ 309.1757, found 309.1769. = 0.69 (cHex/EtOAc/Et3N 4:1:0.01); mp 166C167 C; 1H NMR (500.23 MHz, CDCl3) 7.98 (dd, = 8.0, 2.0 Hz, 1H), 7.42 (s, 1H), 7.34C7.28 (m, 3H), 7.17 (s, 1H), 4.86 (s, 0H), 2.42 (s, 3H), 1.59 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 159.8, 157.8 (d, = 18.5 Hz), 147.3 (d, = 3.5 Hz), 138.4 (d, = 235.5 Hz), 138.2 (d, = LG-100064 11.0 Hz), 129.4, 128.5 (d, = 11.0 Hz), 127.37, 120.6 (d, = 3.5 Hz), 114.7 (d, = 23.0 Hz), 114.4 (d, = 4.5 Hz), 100.1, 51.8, 29.3, 21.4; HRMS (ESI) calcd for C20H21N2ClF+ [M + H]+ 343.1368, found 343.1376. = 0.58 (cHex/EtOAc/Et3N 4:1:0.01); mp 51C54 C; 1H NMR.Additionally, it can be done that withdrawing electron denseness through substituent effects makes ynimines 8 more vunerable to hydrolysis through the cyclization stage. to tolerate aliphatic alkynes, aswell, as demonstrated from the isolation of 9n and 9o, with relatively lower produce for 9n due to the volatility of 1-hexyne. Open up in another window Structure 4 Alkyne and = 0.19 (cHex/EtOAc/Et3N 4:1:0.05); mp 139 C; 1H NMR (500.23 MHz, CDCl3) 8.10C8.03 (m, 3H), 7.68 (dd, = 1.5, 8.5 Hz, 1H), 7.63 (ddd, = 1.5, 7.0, 8.5 Hz, 1H), 7.51 (t, = 7.5 Hz, 2H), 7.47C7.38 (m, 2H), 7.12 (s, 1H), 5.03 (bs, 1H), 1.60 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 157.9, 148.8, 148.3, 141.2, 130.5, 129.0, 128.8, 128.6, 127.5, 124.3, 118.9, 118.5, 99.1, 51.5, 29.4; HRMS (ESI) calcd for C19H21N2+ [M + H]+ 277.1695, found 277.1707. = 0.33 (cHex/EtOAc/Et3N 4:1:0.05); mp 134 C; 1H NMR (500.23 MHz, CDCl3) 8.05 (dd, = 1.5, 7.5 Hz, 2H), 7.85 (s, 1H), 7.57 (d, = 8.5 Hz, 1H), 7.50 (t, = 7.5 Hz, 2H), 7.47C7.40 (m, 1H), 7.23 (dd, = 7.5, 8.5 Hz, 1H), 7.07 (d, = 1.5 Hz, 1H), 4.99 (bs, 1H), 2.52 (s, 3H), 1.59 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 157.9, 149.0, 148.3, 141.3, 139.0, 129.7, 128.7, 128.6, 127.5, 126.4, 118.6, 116.4, 98.7, 51.4, 29.4, 21.5; HRMS (ESI) calcd for C20H23N2+ [M + H]+ 291.1851, found 291.1854. = 0.44 (cHex/EtOAc/Et3N 4:1:0.05); mp 163 C; 1H NMR (500.23 MHz, CDCl3) 8.14C8.06 (m, 3H), 7.54 (t, = 7.5 Hz, 2H), 7.50C7.44 (m, 1H), 7.48C7.37 (m, 1H), 7.36 (dd, = 2.5, 10.0 Hz, 1H), 7.17 (s, 1H), 4.79 (bs, 1H), 1.57 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 159.5 (d, = 245.0 Hz), 157.3 (d, = 2.5 Hz), 147.9 (d, = 4.5 Hz), 145.8, 140.9, 132.8 (d, = 8.5 Hz), 128.8, 128.6, 127.4, 118.9 (d, = 8.0 Hz), 118.6 (d, = 24.5 Hz), 103.3 (d, = 23.0 Hz), 99.4, 51.6, 29.3; HRMS (ESI) calcd for C19H20N2F+ [M + H]+ 295.1601, found 295.1604. = 0.43 (cHex/EtOAc/Et3N 4:1:0.05); mp 155 C; 1H NMR (500.23 MHz, CDCl3) 8.04 (dd, = 5.5, 9.0 Hz, 1H), 7.95 (d, = 8.0 Hz, 2H), 7.42C7.36 (m, 1H), 7.34C7.27 (m, 3H), 7.12 (s, 1H), 4.74 (bs, 1H), 2.43 (s, 3H), 1.59 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 159.5 (d, = 245.0 Hz), 157.3 (d, = 2.5 Hz), 147.8 (d, = 5.0 Hz), 145.8, 138.8, 138.0, 132.7 (d, = 8.5 Hz), 129.4, 127.3, 118.9 (d, = 8.0 Hz), 118.5 (d, = 25.0 Hz), 103.3 (d, = 23.0 Hz), 99.3, 51.5, 29.3, 21.3; HRMS (ESI) calcd for C20H22N2F+ [M + H]+ 309.1757, found 309.1769. = 0.69 (cHex/EtOAc/Et3N 4:1:0.01); mp 166C167 C; 1H NMR (500.23 MHz, CDCl3) 7.98 (dd, = 8.0, 2.0 Hz, 1H), 7.42 (s, 1H), 7.34C7.28 (m, 3H), 7.17 (s, 1H), 4.86 (s, 0H), 2.42 (s, 3H), 1.59 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 159.8, 157.8 (d, = 18.5 Hz), 147.3 (d, = 3.5 Hz), 138.4 (d, = 235.5 Hz), 138.2 (d, = 11.0 Hz), 129.4, 128.5 (d, = 11.0 Hz), 127.37, 120.6 (d, = 3.5 Hz), 114.7 (d, = 23.0 Hz), 114.4 (d, = 4.5 Hz), 100.1, 51.8, 29.3, 21.4; HRMS (ESI) calcd for C20H21N2ClF+ [M + H]+ 343.1368, found 343.1376. = 0.58 (cHex/EtOAc/Et3N 4:1:0.01); mp 51C54 C; 1H NMR (500.23 MHz, CDCl3) 8.08C7.98 (m, 2H), 7.89 (d, = 6.5 Hz, 1H), 7.59 (d, = 9.0 Hz, 1H), 7.47C7.39 (m, 2H), 7.34 (d, = 9.0 Hz, 1H), 7.04 (s, 1H), 5.03 (bs, 1H), 1.59 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 157.3, 149.5, 148.6, 142.5, 135.0, 134.7, 129.9, 129.3, 129.0, 127.6, 125.5, 125.2, 120.5, 117.0, 98.9, 51.7, 29.3; HRMS (ESI) calcd for C19H19N2Cl2+ [M + H]+ 345.0917, found 345.0925. = 0.33 (cHex/EtOAc/Et3N 4:1:0.05); mp 138 C; 1H NMR (500.23 MHz, CDCl3) 8.09C8.01 (m, 3H), 7.68 (d, = 8.5 Hz, 1H), 7.67C7.60 (m, 1H), 7.44C7.37 (m, 1H), 7.19 (t, = 8.5 Hz, 2H), 7.06 (s, 1H), 5.05 (bs, 1H), 1.60 (s, 9H); 13C NMR (125.97 MHz, CDCl3) 163.4 (d, = 248.0 Hz), 156.8, 148.8, 148.4, 137.3 (d, = 3.0 Hz), 130.4, 129.2 (d, = 8.5 Hz), 129.1, 124.4, 118.9, 118.4, 115.5 (d, = 21.5 Hz), 98.7; HRMS (ESI) calcd for C19H20N2F+ [M + H]+ 295.1601, found 295.1601. = 0.38 (cHex/EtOAc/Et3N 4:1:0.01); mp 47C49 C; 1H NMR (500.23 MHz, CDCl3) 8.11C7.99 (m, 2H), 7.78C7.57 (m, 2H), 7.13 (t, = 8.5 Hz, 1H), 7.08C6.93 (m, 3H), 4.97 (bs, 1H),.
Posted inTachykinin, Non-Selective
The perfect solution is was cooled to ?40 C, and triphosgene (1
