All chemicals and reagents were procured form Sigma Aldrich, Spectrochem and CDH, India and utilized without any further purification. All yield mentioned are refer to the isolated compounds after purification process. Characterization of synthesized compounds was done via spectroscopic techniques such as 1H and 13C NMR along with elemental analysis. NMR spectra were recorded on Avance III HD 500 MHz Bruker Biospin and JOEL 400 MHz using DMSO-d6. Chemical shifts in 1H NMR were reported in δ values relative to TMS as internal standard (0.00 ppm). Splitting patter in obtained 1H NMR spectra are reported as s: singlet, d: doublet, m: multiplet, br: broad peak and coupling constants (J) in hertz (Hz).
4.1.3. Procedure for synthesis of morpholinated isatin-quinoline hybrids (AS-1 to AS-18)
1-(2-morpholinoalkyl)indoline-2,3-dione (1 equiv) and 7-chloro-4hydarzinylquinoline (1 equiv) were dissolved in absolute ethanol and few drops of glacial acetic acid was added to it. Reaction mixture was allowed to reflux until both reactants are not completely consumed (monitored by TLC). On completion, reaction mixture was cooled down to room temperature and kept overnight for precipitation. Precipitates so obtained were filtered, washed with ethanol (10 mL) twice and further recrystallized using ethanol to get desired morpholinated isatin-quinoline hybrids. Characterization data of all synthesized morpholinated isatin-quinoline hybrids is as follows:
( Z )-3-(2-(7-chloroquinolin-4-yl)hydrazono)-1-(2-morpholinoethyl)indolin-2-one (AS-1): Yield 76%, 1H NMR (DMSO-d6, 500 MHz, δ, TMS = 0): 12.21 (1H, br), 8.53 (1H, J = 10, d), 8.43–8.41 (1H, m), 7.90 (1H, J = 10, d), 7.85 (1H, m), 7.50–7.47 (1H, m), 7.32–7.28 (1H, m), 7.15 (1H, J = 10, d), 7.08–7.04 (2H, m), 3.85–3.82 (2H, m), 3.50–3.48 (4H, m), 2.53–2.50 (2H, m), 2.42 (4H, s). 13C NMR (DMSO-d6, 125 MHz, δ, TMS = 0): 165.35, 143.48, 142.30, 140.17, 138.64, 136.77, 130.67, 127.45, 125.52, 120.93, 117.96, 109.18, 100.53, 66.71, 55.89, 55.83, 36.99. Anal. Calcd for C23H22ClN5O2: C, 63.37; H, 5.09; N, 16.07; Found: C, 63.34; H, 5.06; N, 16.05.
( Z )-5-bromo-3-(2-(7-chloroquinolin-4-yl)hydrazono)-1-(2-morpholinoethyl)indolin-2-one (AS-2): Yield 68%, 1H NMR (DMSO-d6, 400 MHz, δ, TMS = 0): 12.94 (1H, br), 8.82–8.80 (1H, m), 8.06–8.05 (1H, m), 7.86–7.82 (3H, m), 7.73–7.72 (1H, m), 7.62–7.60 (1H, m), 7.33–7.31 (2H, m) 4.29–4.27 (2H, m), 3.80–3.78 (4H, m), 2.08–2.07 (4H, m), 1.94(2H, s). 13C NMR (DMSO-d6, 100 MHz, δ, TMS = 0): 154.02, 153.89, 152.67, 152.41, 143.33, 139.53, 138.64, 138.60, 128.61, 126.70, 119.50, 115.74, 113.84, 63.53, 58.58, 55.29, 51.88, 19.31. Anal. Calcd for C23H21 BrClN5O2: C, 53.66; H, 4.11; N, 13.60; Found: C, 53.65; H, 4.08; N, 13.57.
( Z )-5-chloro-3-(2-(7-chloroquinolin-4-yl)hydrazono)-1-(2-morpholinoethyl)indolin-2-one (AS-3): Yield 81%, 1H NMR (DMSO-d6, 400 MHz, δ, TMS = 0): 13.63 (1H, br), 8.86–8.85 (1H, m), 8.09 (1H, s), 7.95–7.94 (1H, m), 7.81–7.80 (3H, m), 7.52–7.50 (1H, m), 7.34–7.33 (1H, m), 3.76 (2H, s), 3.54 (4H, s), 2.65 (4H, s), 2.38–2.37 (2H, m). 13C NMR (DMSO-d6, 100 MHz, δ, TMS = 0): 155.16, 154.18, 151.32, 151.04, 142.83, 138.13, 138.05, 137.83, 127.31, 126.10, 118.91, 115.14, 113.14, 62.93, 58.02, 54.79, 51.17, 18.97. Anal. Calcd for C23H21Cl2N5O2: C, 58.73; H, 4.50; N, 14.89; Found: C, 58.69; H, 4.46; N, 14.85.
( Z )-3-(2-(7-chloroquinolin-4-yl)hydrazono)-5-fluoro-1-(2-morpholinoethyl)indolin-2-one (AS-4): Yield 73%, 1H NMR (DMSO-d6, 400 MHz, δ, TMS = 0): 13.64 (1H, br), 8.85 (1H, s), 8.09 (1H, s), 7.95–7.93 (1H, m), 7.81–7.79 (1H, m), 7.76–7.75 (1H, m), 7.63–7.61 (1H, m), 7.34–7.33 (2H, m), 4.07–4.06 (2H, m), 3.63 (4H, s), 2.57–2.53 (2H, s), 2.50 (4H, m). 13C NMR (DMSO-d6, 100 MHz, δ, TMS = 0): 157.13, 155.12, 152.66, 152.14, 143.27, 139.32, 139.13, 138.43, 129.12, 125.16, 119.07, 115.22, 114.23, 62.83, 58.62, 54.89, 51.78, 19.22. Anal. Calcd for C23H21ClFN5O2: C, 60.86; H, 4.66; N, 15.43; Found: C, 60.83; H, 4.62; N, 15.41.
( Z )-3-(2-(7-chloroquinolin-4-yl)hydrazono)-5-methyl-1-(2-morpholinoethyl)indolin-2-one (AS-5): Yield 83%, 1H NMR (DMSO-d6, 400 MHz, δ, TMS = 0): 13.65 (1H, br), 8.84–8.83 (1H, m), 8.08 (1H, s), 7.93–7.92 (1H, m), 7.80–7.78 (1H, m), 7.71–7.70 (1H, m), 7.58 (1H, s), 7.29–7.27 (1H, m), 7.20–7.18 (1H, m), 4.12 (2H, s), 3.61 (4H, s), 2.55 (5H, s), 2.38 (4H, s). 13C NMR (DMSO-d6, 100 MHz, δ, TMS = 0): 157.22, 155.36, 152.64, 152.48, 143.87, 139.22, 138.79, 138.04, 128.79, 125.11, 119.16, 115.94, 114.29, 62.46, 58.36, 54.97, 51.49, 19.82, 18.23. Anal. Calcd for C24H24ClN5O2: C, 64.07; H, 5.38; N, 15.57; Found: C, 64.04; H, 5.36; N, 15.55.
( Z )-3-(2-(7-chloroquinolin-4-yl)hydrazono)-5-methoxy-1-(2-morpholinoethyl)indolin-2-one (AS-6): Yield 86%, 1H NMR (DMSO-d6, 400 MHz, δ, TMS = 0): 13.68 (1H, br), 8.84 (1H, m), 8.09 (1H, s), 7.96–7.92 (1H, m), 7.82–7.76 (2H, m), 7.36 (1H, s), 7.25–7.24 (1H, m), 7.06-7.00 (2H, m), 4.00 (3H, s), 3.77 (2H, s), 3.63 (4H, s), 2.65–2.64 (2H, m), 2.60–2.57 (4H, m). 13C NMR (DMSO-d6, 100 MHz, δ, TMS = 0): 157.16, 155.59, 152.49, 152.47, 143.49, 139.34, 138.47, 138.49, 128.99, 125.46, 119.49, 115.74, 114.97, 62.32, 58.49, 54.22, 51.79, 19.58, 21.64. Anal. Calcd for C24H24ClN5O3: C, 61.87; H, 5.19; N, 15.03; Found: C, 61.85; H, 5.16; N, 15.06.
( Z )-3-(2-(7-chloroquinolin-4-yl)hydrazono)-1-(3-morpholinopropyl)indolin-2-one (AS-7): Yield 76%, 1H NMR (DMSO-d6, 500 MHz, δ, TMS = 0): 12.22 (1H, br), 8.54 (1H, J = 10, d), 8.44–8.40 (1H, m), 7.91 (1H, J = 10, d), 7.86 (1H, m), 7.49–7.46 (1H, m), 7.31–7.26 (1H, m), 7.12 (1H, J = 10, d), 7.06–7.02 (2H, m), 3.88–3.84 (2H, m), 3.52–3.50 (4H, m), 2.51–2.48 (2H, m), 2.10 (4H, s), 1.95–1.93 (2H, m). 13C NMR (DMSO-d6, 125 MHz, δ, TMS = 0): 165.33, 143.47, 142.22, 140.37, 138.49, 136.79, 130.32, 126.51, 125.18, 120.95, 116.22, 109.79, 100.48, 66.39, 55.27, 55.66, 36.41, 24.16. Anal. Calcd for C24H24ClN5O2: C, 64.07; H, 5.38; N, 15.57; Found: C, 64.04; H, 5.34; N, 15.53.
( Z )-5-bromo-3-(2-(7-chloroquinolin-4-yl)hydrazono)-1-(3-morpholinopropyl)indolin-2-one (AS-8): Yield 68%, 1H NMR (DMSO-d6, 400 MHz, δ, TMS = 0): 12.98 (1H, br), 8.81–8.83 (1H, m), 8.05–8.04 (1H, m), 7.85–7.81 (3H, m), 7.75–7.73 (1H, m), 7.60–7.58 (1H, m), 7.31–7.29 (2H, m) 4.28–4.26 (2H, m), 3.82–3.80 (4H, m), 2.10–2.08 (4H, m), 1.96–1.94 (2H, m), 1.92 (2H, s). 13C NMR (DMSO-d6, 100 MHz, δ, TMS = 0): 155.18, 156.32, 153.98, 151.49, 141.22, 139.16, 137.12, 136.27, 128.62, 126.80, 119.92, 115.22, 113.84, 63.32, 58.49, 55.19, 51.17, 24.41, 19.32. Anal. Calcd for C24H23BrClN5O2: C, 54.51; H, 4.38; N, 13.24; Found: C, 54.47; H, 4.35; N, 13.20.
( Z )-5-chloro-3-(2-(7-chloroquinolin-4-yl)hydrazono)-1-(3-morpholinopropyl)indolin-2-one (AS-9): Yield 81%, 1H NMR (DMSO-d6, 400 MHz, δ, TMS = 0): 13.62 (1H, br), 8.85–8.84 (1H, m), 8.09 (1H, s), 7.91–7.89 (1H, m), 7.77–7.76 (3H, m), 7.51–7.49 (1H, m), 7.33–7.32 (1H, m), 3.74 (2H, s), 3.56 (4H, s), 2.63 (4H, s), 2.35–2.33 (2H, m), 1.93–1.91 (2H, m). 13C NMR (DMSO-d6, 100 MHz, δ, TMS = 0): 154.89, 154.12, 152.22, 151.32, 141.53, 137.93, 137.25, 136.83, 127.51, 126.19, 118.53, 115.59, 113.32, 62.22, 58.49, 53.21, 51.49, 23.16, 18.32. Anal. Calcd for C24H23Cl2N5O2: C, 59.51; H, 4.79; N, 14.64; Found: C, 59.47; H, 4.75; N, 14.60.
( Z )-3-(2-(7-chloroquinolin-4-yl)hydrazono)-5-fluoro-1-(3-morpholinopropyl)indolin-2-one (AS-10): Yield 72%, 1H NMR (DMSO-d6, 400 MHz, δ, TMS = 0): 13.64 (1H, br), 8.87 (1H, s), 8.08 (1H, s), 7.95–7.93 (1H, m), 7.81–7.79 (1H, m), 7.76–7.75 (1H, m), 7.61–7.59 (1H, m), 7.31–7.29 (2H, m), 4.15–4.13 (2H, m), 3.51 (4H, s), 2.55–2.53 (2H, s), 2.50 (4H, m), 1.96–1.94 (2H, m). 13C NMR (DMSO-d6, 100 MHz, δ, TMS = 0): 158.22, 155.79, 152.63, 152.05, 143.17, 139.49, 139.02, 138.65, 129.32, 125.27, 118.22, 115.37, 114.21, 62.49, 58.57, 54.34, 51.27, 24.59, 18.36. Anal. Calcd for C24H23ClFN5O2: C, 61.60; H, 4.95; N, 14.97; Found: C, 61.57; H, 4.92; N, 14.93.
( Z )-3-(2-(7-chloroquinolin-4-yl)hydrazono)-5-methyl-1-(3-morpholinopropyl)indolin-2-one (AS-11): Yield 86%, 1H NMR (DMSO-d6, 400 MHz, δ, TMS = 0): 13.63 (1H, br), 8.82–8.80 (1H, m), 8.09 (1H, s), 7.94–7.93 (1H, m), 7.81–7.79 (1H, m), 7.73–7.71 (1H, m), 7.57 (1H, s), 7.28–7.26 (1H, m), 7.21–7.19 (1H, m), 4.14 (2H, s), 3.63 (4H, s), 2.54 (5H, s), 2.35 (4H, s), 1.98–1.96 (2H, m). 13C NMR (DMSO-d6, 100 MHz, δ, TMS = 0): 156.26, 155.17, 152.18, 152.07, 143.22, 139.36, 138.21, 138.17, 128.51, 125.22, 119.37, 115.51, 114.41, 62.37, 58.16, 54.32, 51.48, 24.46, 19.32, 18.26. Anal. Calcd for C25H26ClN5O2: C, 64.72; H, 5.65; N, 15.09; Found: C, 64.69; H, 5.61; N, 15.05.
( Z )-3-(2-(7-chloroquinolin-4-yl)hydrazono)-5-methoxy-1-(3-morpholinopropyl)indoli n-2-one (AS-12): Yield 81%, 1H NMR (DMSO-d6, 400 MHz, δ, TMS = 0): 13.62 (1H, br), 8.82 (1H, m), 8.07 (1H, s), 7.96–7.94 (1H, m), 7.80–7.78 (2H, m), 7.39 (1H, s), 7.23–7.21 (1H, m), 7.12–7.08 (2H, m), 4.12 (3H, s), 3.71 (2H, s), 3.65 (4H, s), 2.64–2.63 (2H, m), 2.59–2.57 (4H, m), 1.95–1.93 (2H, m). 13C NMR (DMSO-d6, 100 MHz, δ, TMS = 0): 157.29, 155.78, 152.23, 152.17, 143.32, 140.29, 138.49, 138.13, 128.31, 125.42, 119.65, 116.41, 114.47, 62.79, 58.34, 54.47, 52.75, 24.87, 21.34, 19.35. Anal. Calcd for C25H26ClN5O3: C, 62.56; H, 5.46; N, 14.59; Found: C, 62.52; H, 5.43; N, 14.57.
( Z )-3-(2-(7-chloroquinolin-4-yl)hydrazono)-1-(4-morpholinobutyl)indolin-2-one (AS-13): Yield 74%, 1H NMR (DMSO-d6, 500 MHz, δ, TMS = 0): 12.23 (1H, br), 8.51 (1H, J = 10, d), 8.45–8.43 (1H, m), 7.88 (1H, J = 10, d), 7.85 (1H, m), 7.46–7.45 (1H, m), 7.32–7.29 (1H, m), 7.14 (1H, J = 10, d), 7.07–7.03 (2H, m), 3.81–3.79 (2H, m), 3.49–3.47 (4H, m), 2.86–2.83 (2H, m), 2.22 (4H, s), 1.75–1.73 (2H, m), 1.51–1.49 (2H, m). 13C NMR (DMSO-d6, 125 MHz, δ, TMS = 0): 165.47, 143.32, 142.41, 140.47, 139.28, 135.51, 132.17, 127.32, 126.22, 121.17, 116.26, 109.69, 100.12, 66.51, 55.23, 55.47, 36.12, 25.27, 24.37. Anal. Calcd for C25H26ClN5O2: C, 64.72; H, 5.65; N, 15.09; Found: C, 64.69; H, 5.63; N, 15.07.
( Z )-5-bromo-3-(2-(7-chloroquinolin-4-yl)hydrazono)-1-(4-morpholinobutyl)indolin-2-one (AS-14): Yield 71%, 1H NMR (DMSO-d6, 400 MHz, δ, TMS = 0): 12.95 (1H, br), 8.86–8.84 (1H, m), 8.07–8.06 (1H, m), 7.83–7.80 (3H, m), 7.76–7.74 (1H, m), 7.62–7.60 (1H, m), 7.33–7.31 (2H, m) 4.29–4.27 (2H, m), 3.80–3.79 (4H, m), 2.11–2.09 (4H, m), 1.95–1.93 (2H, m), 1.90 (2H, s), 1.55–1.53 (2H, m). 13C NMR (DMSO-d6, 100 MHz, δ, TMS = 0): 155.32, 156.27, 153.41, 151.56, 141.37, 139.57, 137.48, 136.42, 128.63, 126.71, 119.64, 115.32, 113.59, 63.41, 58.79, 54.32, 51.48, 25.27, 24.63, 19.47. Anal. Calcd for C25H25 BrClN5O2: C, 55.31; H, 4.64; N, 12.90; Found: C, 55.29; H, 4.63; N, 12.87.
( Z )-5-chloro-3-(2-(7-chloroquinolin-4-yl)hydrazono)-1-(4-morpholinobutyl)indolin-2-one (AS-15): Yield 79%, 1H NMR (DMSO-d6, 400 MHz, δ, TMS = 0): 13.64 (1H, br), 8.82–8.80 (1H, m), 8.09 (1H, s), 7.92–7.91 (1H, m), 7.76–7.73 (3H, m), 7.52–7.51 (1H, m), 7.34–7.33 (1H, m), 3.73 (2H, s), 3.57 (4H, s), 2.63 (4H, s), 2.35–2.33 (2H, m), 1.94–1.92 (2H, m), 1.53–1.50 (2H, m). 13C NMR (DMSO-d6, 100 MHz, δ, TMS = 0): 154.93, 154.22, 152.49, 151.24, 141.47, 137.95, 137.32, 136.48, 127.12, 126.49, 118.27, 115.16, 113.41, 62.32, 58.10, 53.25, 51.47, 25.53, 23.36, 18.32. Anal. Calcd for C25H25Cl2N5O2: C, 60.25; H, 5.06; N, 14.05; Found: C, 60.22; H, 4.99; N, 13.98.
( Z )-3-(2-(7-chloroquinolin-4-yl)hydrazono)-5-fluoro-1-(4-morpholinobutyl)indolin-2-one (AS-16): Yield 76%, 1H NMR (DMSO-d6, 400 MHz, δ, TMS = 0): 13.66 (1H, br), 8.85 (1H, s), 8.09 (1H, s), 7.96–7.94 (1H, m), 7.83–7.81 (1H, m), 7.73–7.71 (1H, m), 7.63–7.61 (1H, m), 7.32–7.30 (2H, m), 4.27–4.25 (2H, m), 3.56 (4H, s), 2.56–2.51 (2H, s), 2.50 (4H, m), 1.95–1.93 (2H, m), 1.49–1.47 (2H, m). 13C NMR (DMSO-d6, 100 MHz, δ, TMS = 0): 158.36, 155.47, 152.32, 152.49, 143.34, 139.97, 139.43, 138.46, 129.05, 125.49, 118.34, 115.61, 114.34, 62.32, 58.49, 54.79, 51.18, 25.69, 24.63, 18.01. Anal. Calcd for C25H25ClFN5O2: C, 62.30; H, 5.23; N, 14.53; Found: C, 62.34; H, 2.19; N, 14.47.
( Z )-3-(2-(7-chloroquinolin-4-yl)hydrazono)-5-methyl-1-(4-morpholinobutyl)indolin-2-one (AS-17): Yield 75%, 1H NMR (DMSO-d6, 400 MHz, δ, TMS = 0): 13.34 (1H, br), 8.81–8.80 (1H, m), 8.08 (1H, s), 7.95–7.94 (1H, m), 7.81–7.80 (1H, m), 7.72–7.70 (1H, m), 7.58 (1H, s), 7.25–7.23 (1H, m), 7.20–7.18 (1H, m), 4.32 (2H, s), 3.59 (4H, s), 2.67 (5H, s), 2.32 (4H, s), 1.95–1.93 (2H, m), 1.54–1.52 (2H, m). 13C NMR (DMSO-d6, 100 MHz, δ, TMS = 0): 155.32, 154.87, 152.11, 152.37, 143.37, 139.47, 138.41, 138.64, 128.48, 125.11, 119.57, 115.48, 114.34, 62.32, 58.49, 54.11, 51.37, 25.57, 24.63, 19.27, 18.41. Anal. Calcd for C26H28ClN5O2: C, 65.33; H, 5.90; N, 14.65; Found: C, 65.29; H, 5.95; N, 14.61.
( Z )-3-(2-(7-chloroquinolin-4-yl)hydrazono)-5-methoxy-1-(4-morpholinobutyl)indolin-2-one (AS-18): Yield 82%, 1H NMR (DMSO-d6, 400 MHz, δ, TMS = 0): 13.60 (1H, br), 8.84 (1H, m), 8.09 (1H, s), 7.98–7.96 (1H, m), 7.81–7.79 (2H, m), 7.40 (1H, s), 7.24–7.22 (1H, m), 7.11–7.07 (2H, m), 4.14 (3H, s), 3.73 (2H, s), 3.61 (4H, s), 2.65–2.64 (2H, m), 2.61–2.59 (4H, m), 1.96–1.94 (2H, m), 1.53–1.51 (2H, m). 13C NMR (DMSO-d6, 100 MHz, δ, TMS = 0): 157.41, 155.38, 152.11, 152.02, 143.37, 140.41, 138.57, 138.49, 128.36, 125.12, 119.31, 116.47, 114.12, 62.37, 58.45, 54.31, 52.23, 25.75, 24.47, 21.21, 19.58. Anal. Calcd for C26H28ClN5O3: C, 63.22; H, 5.71; N, 14.18; Found: C, 62.19; H, 5.66; N, 14.15.