A series of novel 6-(pyrazolylmethyl)-4-oxo-4activity features, it does not influence binding

A series of novel 6-(pyrazolylmethyl)-4-oxo-4activity features, it does not influence binding ability, which can be seen by comparing the strand transfer inhibition IC50 values of GS-9137 and its 7-demethoxy derivative (7. recorded on a Bruker Esquire 6000 mass spectrometer. HRMS spectra were recorded in the positive ion mode using APEX IV FT-ICRMS of Bruker Daltonics Inc. Purities of target compounds 11aCc, 12aCc, 13aCc, 14aCc, 15aCc, 16aCc were determined by an Agilent 1260 HPLC system equipped with a Agilent Zorbax SB-C18 column (5 m, 4.4 25mm), UV detector at 254 nm, mobile phase CH3OH/H2O (70%C100% or 80%) and flow rate of 1 1 mL/min. All solvents were of commercial quality and were purified and dried by standard methods. 3.2. General Process of the formation of Ethyl 1-Substitued-6-(pyrazolylmethyl)-4-oxo-4H-quinoline-3-carboxylates (6a). Produce: 33%; mp: 162C165 C; 1H-NMR (CDCl3, ppm) 1.43 (t, 3H, = 7.2 Hz, -CH2= 4.4 Hz, = 4.4 Hz, = 5.6 and 15.6 Hz, CH2OCH= 7.2 Hz, -= 2.0 and 15.6 Hz, CH2OCH= 2.4 and 8.8 Hz, H7), 7.50 (d, 1H, = 8.8 Hz, H8), 8.32 (d, 1H, = 2.0 Hz, H5), 8.43 (s, 1H, H2). (6b). Produce: 33%; mp: 200C202 C; 1H-NMR (CDCl3, ppm) 1.42 (t, 3H, = 6.8 Hz, -CH2= 4.8 Hz, = 4.4 Hz, = 6.0 and 15.6 Hz, CH2OCH= 7.0 Hz, -= 2.0 and 15.6 Hz, CH2OCH= 2.4 and 8.8 Hz, H7), 7.51 (d, 1H, = 8.8 Hz, H8), 8.33 (d, 1H, = 2.0 Hz, H5), 8.43 (s, 1H, H2). (6c). Produce: 47%; mp: 199C201 C; Endoxifen supplier 1H-NMR (CDCl3, ppm) 1.42 (t, 3H, = 7.2 Hz, -CH2= 4.4 Hz, = 4.4 Hz, = 6.0 and 15.6 Hz, CH2OCH= 7.2 Hz, -= 2.4 and 15.6 Hz, CH2OCH= 2.0 and 8.8 Hz, H7), 7.50 (d, 1H, = 8.8 Hz, H8), 8.31 (d, 1H, = 2.0 Hz, H5), 8.42 (s, 1H, H2); 13C-NMR (CDCl3, 100 MHz, ppm) 10.4, 12.3, 14.4, 45.2, 49.6, 53.1, 54.8, 60.9, 94.8, 111.6, 116.7, 125.9, 128.8, 131.5, 133.9, 137.4, 138.8, 146.6, 149.4, 165.4, 173.8; ESI-MS: 459.9, 461.9 [M+H]+. (7a). Produce: 53%; mp: 225C228 C; Endoxifen supplier 1H-NMR (CDCl3, ppm) 1.41 (t, 3H, = 7.2 Hz, -CH2= 7.0 Hz, -= 8.8 Hz, H8), 7.40 (dd, 1H, = 2.0 and 8.4 Hz, H7), 8.28 (d, 1H, = 2.0 Hz, H5), 8.39 (s, 1H, H2). (7b). Produce: 43%; mp: 235C237 C; 1H-NMR (CDCl3, ppm) 1.43 (t, 3H, = 7.2 Hz, -CH2= 7.2 Hz, -= 8.4 Hz, H8), 7.40 (dd, 1H, = 2.4 and 8.8 Hz, H7), 8.32 (d, 1H, = 2.0 Hz, H5), 8.39 (s, 1H, H2). (7c). Produce: 55%; mp: 239C242 C; 1H-NMR (CDCl3, ppm) 1.43 (t, 3H, = 7.2 Hz, -CH2= 7.2 Hz, -= 8.8 Hz, H8), 7.40 (dd, 1H, = 2.0 and 8.4 Hz, H7), 8.33 (d, 1H, = 2.0 Hz, H5), 8.41 (s, 1H, H2); ESI-MS: 476, 478 [M+H]+, 498, 500 [M+Na]+, 514, 516 [M+K]+. (8a). Produce: 49%; mp: 125C128 C; 1H-NMR (CDCl3, ppm) 1.43 (t, 3H, = 7.2 Hz, -CH2= 6.4 Hz, -CH2CH2= 7.6 Hz, -= 7.0 Hz, -= 8.4 Hz, H2); 13C-NMR (CDCl3, ppm) 11.1, 13.5, 14.4, 25.7, 28.9, 30.6, 51.9, 52.4, 60.9, 105.8, 111.4, 116.2, 126.1, 129.2, 131.5, 134.7, 138.1, 139.3, 147.9, 148.8, 165.7, 173.9, 194.9; ESI-MS: 441.9 [M+H]+, 463.9 [M+Na]+, 479.8 [M+K]+. (8b). Produce: 51%; Endoxifen supplier mp: 122C125 C; 1H-NMR (CDCl3, ppm) 1.43 (t, 3H, = 7.2 Hz, -CH2= 6.8 Hz, -CH2CH2= 7.6 Hz, -= 7.2 Hz, -= 2.0 Hz, H5), 8.45 (s, 1H, H2). (8c). Produce: 46%; mp: 141C143 C; 1H-NMR (CDCl3, ppm) 1.43 (t, 3H, = 7.2 Hz, -CH2= 6.8 Hz, -CH2CH2= 7.6 Hz, -= 7.2 Hz, -= 1.6 Hz, H5), 8.46 (s, 1H, H2). (9a). Produce: 50%; mp: 209C211 C; 1H-NMR (CDCl3, ppm) 1.43 (t, 3H, = 7.2 Hz, -CH2= 7.0 Hz, -= 6.4 Hz, Ar-= 8.8 Hz, Ar-= 8.8 Hz, H8), 7.29 (dd, 1H, = 2.0 and 8.8 Hz, H7), 8.30 (d, 1H, = 2.0 Hz, H5), 8.57 (s, 1H, H2); ESI-MS: 433.9 [M+H]+, 455.9 [M+Na]+, 471.8 [M+K]+. (9b). Produce: 51%; mp: 226C228 C; 1H-NMR (CDCl3, ppm) 1.44 (t, 3H, = 7.2 Hz, -CH2= 7.2 Hz, -= 6.8 Hz, Ar-= 8.0 Hz, Ar-= 8.8 Hz, H8), 7.30 (dd, 1H, = 2.4 and 8.8 Hz, H7), 8.32 (d, 1H, = 1.6 Hz, H5), 8.58 (s, 1H, H2); ESI-MS: 467.9 [M+H]+. (9c). Produce: 55%; mp: 219C221 Endoxifen supplier C; 1H-NMR (CDCl3, ppm) 1.44 (t, 3H, = 7.2 Hz, -CH2= 7.0 Hz, -= 8.4 Hz, Ar-= 9.2 Hz, Ar-= 8.8 Hz, H8), 7.31 (dd, Rabbit Polyclonal to TGF beta Receptor II 1H, = 2.0 and 8.8 Hz, H7), 8.30 (d, 1H,= 1.2 Hz, H5), 8.59 (s, 1H, H2); ESI-MS: 521, 514 [M+H]+, 534, 536 [M+Na]+, 550, 552 [M+K]+. (10a). Produce: 49%; mp: 194C196 C; 1H-NMR (CDCl3, ppm) 1.43 (t, 3H, = 7.2 Hz, -CH2= 7.2 Hz, -= 8.8 Hz, H8), 7.24 (dd, 1H, = 2.4 and 8.8 Hz, H7), 7.31 (d, 2H, = 8.8 Hz, Ar-= 6.0.