HRMS (ESI) m/z calcd for C27H29N6O5 [M + H]+ 517.2199, found 517.2207; IR (KBr) .max/cm-1: 3447, 2980, 1740, 1663, 1518, 1298, 1193, 1021, 818; HPLC: 100 %, tr 15.3 min; Anal. Calcd. for C27H28N6O5 . . H2O: C, 61.91; H, 5.48; N, 15.99. Found: C, 61.70; H, 5.56; N, 15.99%.
Ethyl 2-((2-(([1,2,4]triazolo[4,3-b]pyridazin-6-yloxy)methyl)-2,4-dimethyl-3,4-dihydro-2H- 1,4-benzoxazin-7-yl)(4-fluorobenzyl)amino)-2-oxoacetate (14b). White powder, yield 2.6 g (52%); mp 73-75 °C; 1H NMR (400 MHz, DMSO-d6): . 0.72 (t, J 7.1 Hz, 3H, CH2CH3), 1.32 (s, 3H, 2-CH3), 2.78 (s, 3H, N-CH3), 3.01 (d, J 11.9 Hz, 1H, 3-H), 3.27 (d, overlapped with water, 1H, 3-H), 3.84 (q, J 7.1 Hz, 2H, CH2CH3), 4.22 (d, J 11.1 Hz, 1H, CH2O), 4.26 (d, h 11.1 Hz, 1H, CH2O), 4.76 (s, 2H, Ph-CH2), 6.44-6.51 (m, 2H, Ar-H5, Ar-H6), 6.60 (d, J 8.3 Hz, 1H, Ar- H8), 7.02-7.11 (m, 3H, Ph-H3, H5, Ar-H7'), 7.11-7.17 (m, 2H, Ph-H2, H6), 8.22 (d, J 9.8 Hz, 1H, Ar-H8'), 9.34 (s, 1H, Ar-H3'); 13C NMR (DMSO-d6): . 162.5, 161.7, 160.4, 142.5, 141.9, 138.9, 135.2, 132.6, 132.5, 130.0, 129.9, 128.7, 126.6, 120.6, 116.6, 115.4, 115.2, 114.8, 111.8, 73.9, 69.8, 61.0, 53.3, 50.1, 38.0, 20.5, 13.3; HRMS (ESI) m/z calcd for C27H28FN6O5 [M + H]+ 535.2105, found 535.2118; IR (KBr) .max/cm-1: 3447, 2981, 1741, 1664, 1509, 1219, 1022, 820; HPLC: 100 %, tr 15.6 min; Anal. Calcd. for C27H27FN6O5 . . H2O: C, 59.87; H, 5.14; N, 15.21. Found: C, 59.66; H, 5.19; N, 15.46%.
Ethyl 2-((2-(([1,2,4]triazolo[4,3-b]pyridazin-6-yloxy)methyl)-2,4-dimethyl-3,4-dihydro-2H- 1,4-benzoxazin-7-yl)(3,5-difluorobenzyl)amino)-2-oxoacetate (14c). White powder, yield 2.7 g (56%); mp 71-73 °C; 1H NMR (400 MHz, DMSO-d6): . 0.81 (t, J 7.1 Hz, 3H, CH2CH3), 1.40 (s, 3H, 2-CH3), 2.86 (s, 3H, N-CH3), 3.10 (d, J 11.9 Hz, 1H, 3-H), 3.35 (d, overlapped with water, 1H, 3-H), 3.94 (q, J 7.1 Hz, 2H, CH2CH3), 4.29 (d, J 11.1 Hz, 1H, CH2O), 4.34 (d, J 11.1 Hz, 1H, CH2O), 4.88 (s, 2H, Ph-CH2), 6.58-6.64 (m, 2H, Ar-H5, Ar-H6), 6.70 (d, J 8.4 Hz, 1H, Ar-H8), 6.86-6.92 (m, 2H, Ph), 7.13 (d, J 9.9 Hz, 1H, Ar-H7'), 7.12-7.19 (m, 1H, Ph), 8.30 (dd, J 9.9, 0.8 Hz, 1H, Ar-H8'), 9.43 (d, J 0.7 Hz, 1H, Ar-H3'); 13C NMR (DMSO-d6): . 162.4, 161.8, 160.4, 142.5, 142.0, 139.0, 135.3, 128.7, 126.6, 120.4, 116.6, 114.5, 111.9, 111.0, 110.9, 110.9, 110.8, 74.0, 69.8, 64.9, 61.2, 53.3, 50.1, 38.0, 20.5, 15.2, 13.3; HRMS (ESI) m/z calcd for C27H27 F2N6O5 [M + H]+ 553.2011, found 553.2036; IR (KBr) .max/cm-1: 3445, 2980, 1733, 1653, 1510, 1300, 1189, 1025, 818; HPLC: 97.1 %, tr 16.5 min. Anal. Calcd. for C27H26F2N6O5 . 1/3 H2O: C, 58.09; H, 4.75; N, 14.90. Found: C, 58.06; H, 4.81; N, 15.05%.
Ethyl 2-(benzyl(2,4-dimethyl-2-(((3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)oxy)methyl) -3,4-dihydro-2H-1,4-benzoxazin-7-yl)amino)-2-oxoacetate (15a). White powder, yield 2.9 g (60%); mp 75-77 °C; 1H NMR (400 MHz, DMSO-d6): . 0.84 (t, J 7.1 Hz, 3H, CH2CH3), 1.38 (s, 3H, 2-CH3), 2.57 (s, 3H, 3'-CH3), 2.84 (s, 3H, N-CH3), 3.09 (d, J 11.9 Hz, 1H, 3-H), 3.33 (d, overlapped with water, 1H, 3-H), 3.95 (q, J 7.1 Hz, 2H, CH2CH3), 4.36 (d, J 11.1 Hz, 1H, CH2O), 4.33 (d, J 11.0 Hz, 1H, CH2O), 4.84 (s, 2H, Ph-CH2), 6.52-6.60 (m, 2H, Ar-H5, Ar-H6), 6.68 (d, J 8.5 Hz, 1H, Ar-H8), 7.05 (d, J 9.8 Hz, 1H, Ar-H7'), 7.12-7.37 (m, 5H, Ph), 8.22 (d, J 9.8 Hz, 1H, Ar-H8'); 13C NMR (DMSO-d6): . 162.6, 161.7, 159.9, 146.0, 142.7, 141.9, 136.3, 135.2, 129.0, 128.5, 127.8, 127.4, 126.7, 120.5, 115.5, 114.7, 111.9, 74.1, 69.5, 61.0, 53.2, 50.8, 38.1, 20.7, 13.3, 9.2 (two more peaks overlapped with DMSO); HRMS (ESI) m/z calcd for C28H31N6O5 [M + H]+ 531.2356, found 531.2345; IR (KBr) .max/cm-1: 3435, 2980, 1741, 1664,
