2.1.5. General Procedure for the Preparation of the Target Compounds 6a1-a32Substituted quinazolinone (1 mmol, 5a1-a32) was added to 10 mL DMF and stirred to dissolve. KOH (59 mg, 1.05) was added and left to react for 40 min, after which 4 (299 mg, 1 mmol) was added. The reaction was carried out at room temperature for 1–3 h. The reaction was detected by TLC, followed by the addition and stirring of 20 mL of saturated ammonium chloride solution for 5 min. It was then extracted with dichloromethane (20 mL × 3), dried over anhydrous sodium sulfate, filtered, concentrated, and purified (Scheme 3).

3-(difluoromethyl)-1-methyl-N-(2-((4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1H-pyrazole-4-carboxamide (6a1), pale white powder, yield 83%, m.p. 172.8–174.7 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.21 (s, 1H, NH), 8.54 (s, 1H, pyrazol-H5), 8.50 (s, 1H, H2), 8.17 (dd, J = 8.0, 1.5 Hz, 1H, H5), 7.84 (ddd, J = 8.4, 7.1, 1.5 Hz, 1H, H7), 7.70 (dd, J = 8.1, 1.1 Hz, 1H, H8), 7.55 (ddd, J = 8.2, 7.1, 1.2 Hz, 1H, H6), 7.49 (dd, J = 8.0, 1.3 Hz, 1H, Ar-H2), 7.35 (td, J = 7.6, 1.8 Hz, 1H, Ar-H3), 7.31 (t, J = 54.3 Hz, 1H, CF2H), 7.28 (dd, J = 7.8, 1.8 Hz, 1H, Ar-H5), 7.23 (dd, J = 7.6, 1.4 Hz, 1H, Ar-H4), 5.23 (s, 2H,CH2), 4.01 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.63, 160.22, 147.93, 147.90, 145.18 (t, J = 23.1 Hz), 135.36, 134.59, 132.90, 131.20, 128.48, 128.22, 127.28, 127.25, 126.40, 126.20, 126.17, 121.40, 115.91 (t, J = 3.7 Hz), 109.64 (t, J = 234.6 Hz), 59.77, 45.87. HRMS (ESI): calculated for C21H17F2N5O2 [M+Na]+: 432.12425, found: 432.12577.

3-(difluoromethyl)-1-methyl-N-(2-((5-methyl-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1H-pyrazole-4-carboxamide (6a2), white powder, yield 71%, m.p. 223.1–224.2 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.22 (s, 1H,NH), 8.55 (s, 1H, pyrazol-H5), 8.44 (s, 1H, H2), 7.65 (t, J = 7.7 Hz, 1H, H7), 7.53–7.47 (m, 2H, H8, Ar-H2), 7.35 (td, J = 7.6, 1.7 Hz, 1H, Ar-H3), 7.32–7.26 (m, 3H, CF2H, H6, Ar-H5), 7.22 (td, J = 7.5, 1.3 Hz, 1H, Ar-H4), 5.17 (s, 2H, CH2), 3.99 (s, 3H, pyrazol-CH3), 2.73 (s, 3H, 5-CH3). 13C NMR (100 MHz, DMSO-d6) δ 161.20, 160.14, 149.54, 147.58, 145.15 (t, J = 23.1 Hz), 140.22, 135.44, 133.67, 132.93, 131.23, 129.60, 128.62, 128.20, 126.15, 126.07, 125.49, 119.85, 115.94 (t, J = 3.7 Hz), 109.61 (t, J =234.7 Hz), 45.60, 39.48, 22.73. HRMS (ESI): calculated for C22H19F2N5O2 [M+Na]+: 446.13990, found: 446.13964.

3-(difluoromethyl)-1-methyl-N-(2-((6-methyl-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1H-pyrazole-4-carboxamide (6a3), white powder, yield 72%, m.p. 258.8–260.1 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.21 (s, 1H, NH), 8.54 (s, 1H, pyrazol-H5), 8.43 (s, 1H, H2), 7.99–7.90 (m, 1H, H5), 7.66 (dd, J = 8.4, 2.1 Hz, 1H, H7), 7.60 (d, J = 8.3 Hz, 1H, H8), 7.49 (dd, J = 8.0, 1.2 Hz, 1H, Ar-H2), 7.38–7.31 (m, 1H, Ar-H3), 7.31 (t, J = 54.3 Hz, 1H, CF2H), 7.25 (dd, J = 7.8, 2.0 Hz, 1H, Ar-H5), 7.23–7.18 (m, 1H, Ar-H4), 5.22 (s, 2H, CH2), 4.01 (s, 3H, pyrazol-CH3), 2.44 (s, 3H, 6-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.54, 160.16, 147.06, 145.96, 145.15 (t, J = 23.1 Hz), 137.11, 135.88, 135.31, 132.87, 131.20, 128.37, 128.17, 127.12, 126.36, 126.14, 125.48, 121.12, 115.89 (t, J = 3.7 Hz), 109.62 (t, J = 234.7 Hz), 45.73, 39.52, 20.82. HRMS (ESI): calculated for C22H19F2N5O2 [M+Na]+: 446.13975, found: 446.13990.

3-(difluoromethyl)-1-methyl-N-(2-((7-methyl-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1H-pyrazole-4-carboxamide (6a4), white powder, yield 61%, m.p. 246.5–246.8 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.24 (s, 1H, NH), 8.55 (s, 1H, pyrazol-H5), 8.48 (s, 1H, H2), 8.06 (d, J = 8.1 Hz, 1H, H5), 7.54–7.47 (m, 2H, H6,Ar-H2), 7.38 (dd, J = 8.4, 1.8 Hz, 1H, H8), 7.36–7.32 (m, 1H, Ar-H3), 7.31 (t, J = 54.3 Hz, 1H, CF2H), 7.27 (dd, J = 7.8, 1.7 Hz, 1H, Ar-H5), 7.21 (td, J = 7.5, 1.3 Hz, 1H, Ar-H4), 5.21 (s, 2H, CH2), 4.01 (s, 3H, pyrazol-CH3), 2.46 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.54, 160.16, 148.08, 147.94, 145.25, 145.16 (t, J = 23.3 Hz), 135.36, 132.87, 131.10, 128.70, 128.50, 128.21, 126.85, 126.27, 126.09, 126.06, 118.97, 115.91 (t, J = 3.7 Hz), 109.63 (t, J = 234.5 Hz), 45.71, 39.52, 21.31. HRMS (ESI): calculated for C22H19F2N5O2 [M+Na]+: 446.13990, found: 446.13975.

3-(difluoromethyl)-1-methyl-N-(2-((8-methyl-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1H-pyrazole-4-carboxamide (6a5), white powder, yield 76%, m.p. 215.8–216.6 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.22 (s, 1H, NH), 8.54 (s, 1H, pyrazol-H5), 8.53 (s, 1H, H2), 8.01 (ddd, J = 8.0, 1.6, 0.7 Hz, 1H, H5), 7.70 (ddd, J = 7.3, 1.6, 0.9 Hz, 1H, H7), 7.49 (dd, J = 8.0, 1.3 Hz, 1H, H6), 7.47–7.42 (m, 1H, Ar-H2), 7.38–7.32 (m, 1H, Ar-H3), 7.31 (t, J = 54.16 Hz, 1H, CF2H), 7.26 (dd, J = 7.8, 1.9 Hz, 1H, Ar-H5), 7.24–7.18 (m, 1H, Ar-H4), 5.21 (s, 2H, CH2), 4.01 (s, 3H, pyrazol-CH3), 2.54 (s, 3H, 8-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.85, 160.19, 146.95, 146.41, 145.15 (t, J = 23.2 Hz), 135.52, 135.31, 134.94, 132.89, 131.16, 128.39, 128.19, 126.82, 126.32, 126.15, 123.87, 121.33, 115.89 (t, J = 3.4 Hz), 109.63 (t, J = 234.4 Hz), 45.82, 39.31, 17.03. HRMS (ESI): calculated for C22H19F2N5O2 [M+Na]+: 446.13990, found: 446.13975.

3-(difluoromethyl)-N-(2-((7,8-dimethyl-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1-methyl-1H-pyrazole-4-carboxamide (6a6), white powder, yield 61%, m.p. 269.0–270.4 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.25 (s, 1H, NH), 8.54 (s, 1H, pyrazol-H5), 8.51 (s, 1H, H2), 7.93 (d, J = 8.1 Hz, 1H, H5), 7.50 (dd, J = 8.0, 1.3 Hz, 1H, H6), 7.37 (d, J = 8.2 Hz, 1H, Ar-H2), 7.33 (dd, J = 7.9, 1.8 Hz, 1H, Ar-H3), 7.30 (t, J = 54.1 Hz, 1H, CF2H), 7.26 (dd, J = 7.8, 1.7 Hz, 1H, Ar-H5), 7.24–7.18 (m, 1H, Ar-H4), 5.20 (s, 2H, CH2), 4.01 (s, 3H, pyrazol-CH3), 2.48 (s, 3H, 8-CH3), 2.40 (s, 3H, 7-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.92, 160.15, 146.71, 146.12, 145.15 (t, J = 23.5 Hz), 143.28, 135.33, 133.50, 132.87, 131.06, 128.99, 128.44, 128.19, 126.20, 126.08, 123.05, 119.24, 115.92 (t, J = 3.6 Hz), 109.63 (t, J = 234.7 Hz), 45.62, 39.52, 20.46, 12.77. HRMS (ESI): calculated for C23H21F2N5O2 [M+Na]+: 460.15555, found: 460.15515.

3-(difluoromethyl)-N-(2-((5-fluoro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1-methyl-1H-pyrazole-4-carboxamide (6a7), white powder, yield 66%, m.p. 243.1–244.5 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.11 (s, 1H, NH), 8.52 (s, 1H, pyrazol-H5), 8.45 (s, 1H, H2), 7.81 (td, J = 8.2, 5.5 Hz, 1H, H7), 7.50 (dd, J = 8.3, 1.0 Hz, 1H, H8), 7.44 (dd, J = 8.0, 1.3 Hz, 1H, H6), 7.38–7.29 (m, 2H, Ar-H2, Ar-H3), 7.28 (t, J = 54.1 Hz, 1H, CF2H), 7.27–7.20 (m, 2H, Ar-H4, Ar-H5), 5.17 (s, 2H, CH2), 3.99 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) 160.34 (d, J = 263.6 Hz, 1H), 160.26, 159.03, 157.54 (d, J = 3.8 Hz, 1H), 157.52, 150.09, 148.88, 145.13 (t, J = 23.0 Hz), 135.33, 135.24 (d, J = 10.6 Hz, 1H), 132.22 (d, J = 153.8 Hz, 1H), 128.40, 128.17, 126.45, 123.36 (d, J = 33.7 Hz, 1H), 115.81 (t, J = 3.6 Hz), 113.60 (d, J = 20.6 Hz, 1H), 111.11 (d, J = 5.8 Hz, 1H), 109.60 (t, J = 235.3 Hz), 45.73, 39.49. HRMS (ESI): calculated for C21H16F3N5O2 [M+Na]+: 450.11483, found: 450.11509.

3-(difluoromethyl)-N-(2-((6-fluoro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1-methyl-1H-pyrazole-4-carboxamide (6a8), white powder, yield 59%, m.p. 235.4–237.4 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.19 (s, 1H, NH), 8.53 (s, 1H, pyrazol-H5), 8.48 (s, 1H, H2), 7.84 (dd, J = 8.7, 2.8 Hz, 1H, H5), 7.81–7.70 (m, 2H, H7), 7.46 (dd, J = 8.0, 1.3 Hz, 1H, Ar-H2), 7.39–7.31 (m, 2H, H8, Ar-H3), 7.27 (t, J = 54.1 Hz, 1H, CF2H), 7.26–7.18 (m, 2H, Ar-H4, Ar-H5), 5.22 (s, 2H, CH2), 4.01 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.35 (d, J = 245.6 Hz), 160.22, 159.97 (d, J = 3.2 Hz), 159.13, 154.86, 147.38, 145.15 (t, J = 23.0 Hz), 144.83, 135.36, 132.91, 131.14, 130.8 (d, J = 8.4 Hz), 128.41 (d, J = 28.2 Hz), 126.39 (d, J = 32.0 Hz), 123.10 (d, J = 24.1 Hz), 122.71 (d, J = 8.7 Hz), 115.83 (t, J = 3.7 Hz), 110.86 (d, J = 23.5 Hz), 109.60 (t, J = 235.3 Hz), 45.98, 39.49. HRMS (ESI): calculated for C21H16F3N5O2 [M+Na]+: 450.11483, found: 450.11509.

3-(difluoromethyl)-N-(2-((7-fluoro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1-methyl-1H-pyrazole-4-carboxamide (6a9), white powder, yield 62%, m.p. 229.8–230.4 °C. 1H NMR (400 MHz, DMSO) δ 10.18 (s, 1H, NH), 8.53 (s, 1H, pyrazol-H5), 8.52 (s, 1H, H2), 8.24–8.11 (m, 2H, H5,H6), 7.51–7.45 (m, 1H, H8), 7.42 (d, J = 2.6 Hz, 1H, Ar-H2), 7.36–7.32 (m, 1H, Ar-H3), 7.29 (t, J = 54.1 Hz, 1H, CF2H), 7.27 (dd, J = 7.7, 1.8 Hz, 1H, Ar-H5), 7.22 (td, J = 7.4, 1.3 Hz, 1H, Ar-H4), 5.21 (s, 2H, CH2), 4.01 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 165.71 (d, J = 251.6 Hz), 160.22, 159.92, 150.11 (d, J = 13.2 Hz), 149.32, 146.94, 145.16 (t, J = 23.2 Hz), 135.34, 132.91, 131.22, 129.40 (d, J = 10.9 Hz), 128.36(d, J = 24.3 Hz), 126.54, 126.23, 118.49, 115.88 (d, J = 23.6 Hz), 115.85 (t, J = 3.6 Hz), 112.30 (d, J = 21.5 Hz),109.61 (t, J = 234.7 Hz), 45.93, 39.48. HRMS (ESI): calculated for C21H16F3N5O2 [M+Na]+: 450.11483, found: 450.11509.

3-(difluoromethyl)-N-(2-((8-fluoro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1-methyl-1H-pyrazole-4-carboxamide (6a10), white powder, yield 69%, m.p. 274.8–276.2 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.13 (s, 1H, NH), 8.51 (s, 1H, pyrazol-H5), 8.50 (s, 1H, H2), 7.95 (dd, J = 8.5, 1.3 Hz, 1H, H5), 7.76–7.69 (m, 1H, H7), 7.57–7.52 (m, 1H, Ar-H6), 7.44 (dd, J = 7.8, 1.2 Hz, 1H, Ar-H2), 7.38–7.31 (m, 1H, Ar-H3), 7.27(t, J = 54.1 Hz, 1H, CF2H), 7.27–7.20 (m, 2H, Ar-H4, Ar-H5), 5.22 (s, 2H, CH2), 4.00 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.25, 159.69 (d, J = 3.3 Hz), 156.41 (d, J = 254.3 Hz), 148.56, 145.15 (t, J = 23.2 Hz), 137.16 (d, J = 12.3 Hz), 135.29, 132.92, 131.32, 128.34, 128.24, 127.65 (d, J = 7.9 Hz), 126.63, 126.32, 123.49, 121.95 (d, J = 4.2 Hz), 119.97 (d, J = 16.0 Hz), 115.82 (t, J = 3.6 Hz), 109.61 (t, J = 234.7 Hz), 46.12, 39.72. HRMS (ESI): calculated for C21H16F3N5O2 [M+Na]+: 450.11483, found: 450.11509.

3-(difluoromethyl)-N-(2-((6,7-difluoro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1-methyl-1H-pyrazole-4-carboxamide (6a11), white powder, yield 69%, m.p. 243.1–244.5 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.15 (s, 1H, NH), 8.52 (s, 1H, pyrazol-H5), 8.52 (s, 1H, H2), 8.06 (dd, J = 10.4, 8.6 Hz, 1H, H5), 7.78 (dd, J = 11.3, 7.3 Hz, 1H, H8), 7.46 (dd, J = 8.1, 1.3 Hz, 1H, Ar-H2), 7.35 (td, J = 7.5, 1.7 Hz, 1H, Ar-H3), 7.32–7.28 (m, 1H, Ar-H5), 7.28(t, J = 54.1 Hz, 1H, CF2H), 7.23 (td, J = 7.5, 1.3 Hz, 1H, Ar-H4), 5.21 (s, 2H, CH2), 4.01 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.22, 159.37 (d, J = 2.9 Hz), 153.89 (dd, J = 54.6, 14.6 Hz), 148.89 (dd, J = 249.1, 14.2 Hz), 148.80 (d, J = 2.0 Hz), 145.16 (t, J = 23.1 Hz), 135.37, 132.88, 131.05, 128.61, 128.33, 126.59, 126.24, 118.81 (dd, J = 6.7, 2.0 Hz), 115.80 (t, J = 3.6 Hz), 115.31 (d, J = 17.7 Hz), 113.78 (d, J = 19.4 Hz), 109.59 (t, J = 234.7 Hz), 46.09, 39.72. HRMS (ESI): calculated for C21H16F4N5O2 [M+Na]+: 468.10541, found: 468.10521.

N-(2-((5-chloro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (6a12), white powder, yield 58%, m.p. 172.8–174.7 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.14 (s, 1H, NH), 8.53 (s, 1H, pyrazol-H5), 8.49 (s, 1H, H2), 7.78–7.70 (m, 1H, H7), 7.62 (dt, J = 8.2, 1.4 Hz, 1H, H6), 7.56 (dq, J = 7.8, 1.2 Hz, 1H, H8), 7.46 (dt, J = 8.0, 1.4 Hz, 1H, Ar-H2), 7.42–7.29 (m, 2H, CF2H, Ar-H3), 7.28–7.11 (m, 2H, Ar-H4, Ar-H5), 5.16 (s, 2H, CH2), 3.99 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.22, 158.57, 150.42, 148.65, 145.14 (t, J = 23.0 Hz), 135.44, 134.37, 132.98, 132.50, 131.25, 129.71, 128.69, 128.27, 126.92, 126.44, 126.21, 118.50, 115.83 (t, J = 3.7 Hz), 109.59 (t, J = 234.7 Hz), 46.08, 39.70. HRMS (ESI): calculated for C21H16ClF2N5O2 [M+Na]+: 446.08528, found: 466.08523.

N-(2-((6-chloro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (6a13), white powder, yield 66%, m.p. 259.1–260.4 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.36 (s, 1H, NH), 8.69 (s, 1H, pyrazol-H5), 8.52 (s, 1H, H2), 8.07 (d, J = 2.5 Hz, 1H, H5), 7.85 (dd, J = 8.8, 2.5 Hz, 1H, H7), 7.71 (d, J = 8.7 Hz, 1H, H8), 7.43 (dd, J = 8.0, 1.3 Hz, 1H, Ar-H2), 7.36–7.31 (m, 1H, Ar-H3), 7.26(t, J = 54.1 Hz, 1H, CF2H), 7.25–7.18 (m, 2H, Ar-H4, Ar-H5), 5.26 (s, 2H, CH2), 4.00 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.29, 159.56, 148.40, 146.63, 145.15 (t, J = 23.0 Hz), 135.39, 134.63, 133.15, 131.52, 131.31, 130.98, 128.51, 128.16, 126.86, 126.20, 125.13, 122.72, 115.81 (t, J = 3.7 Hz), 109.59 (t, J = 234.7 Hz), 46.14, 39.52. HRMS (ESI): calculated for C21H16ClF2N5O2 [M+Na]+: 446.08528, found: 466.08523.

N-(2-((7-chloro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (6a14), white powder, yield 63%, m.p. 250.3–252.3 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.14 (s, 1H, NH), 8.51 (s, 1H, pyrazol-H5), 8.50 (s, 1H, H2), 8.14 (d, J = 8.6 Hz, 1H, H5), 7.76 (d, J = 2.1 Hz, 1H, H8), 7.59 (dd, J = 8.5, 2.1 Hz, 1H, H6), 7.45 (dd, J = 7.9, 1.3 Hz, 1H, Ar-H2), 7.35 (td, J = 7.5, 1.9 Hz, 1H, Ar-H3),7.28 (t, J = 54.1 Hz, 1H, CF2H), 7.27–7.19 (m, 2H, Ar-H4, Ar-H5), 5.20 (s, 2H, CH2), 4.00 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.22, 160.00, 149.38, 149.01, 145.13 (t, J = 23.2 Hz), 139.21, 135.31, 132.88, 131.24, 128.45, 128.29, 128.26, 127.55, 126.59, 126.42, 126.27, 120.29, 115.82(t, J = 3.6 Hz), 109.60 (t, J = 234.6 Hz), 46.02, 39.75. HRMS (ESI): calculated for C21H16ClF2N5O2 [M+Na]+: 446.08528, found: 466.08523.

N-(2-((8-chloro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (6a15), white powder, yield 68%, m.p. 231.8–233.0 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.13 (s, 1H, NH), 8.58 (s, 1H, pyrazol-H5), 8.50 (s, 1H, H2), 8.10 (dd, J = 7.7, 1.2 Hz, 1H, H5), 7.99 (dd, J = 7.8, 1.4 Hz, 1H, H7), 7.56–7.50 (m, 1H, H6), 7.44 (dd, J = 7.9, 1.3 Hz, 1H, Ar-H2), 7.35 (ddd, J = 8.1, 6.7, 2.2 Hz, 1H, Ar-H3), 7.29(t, J = 54.1 Hz, 1H, CF2H), 7.28–7.20 (m, 2H, Ar-H4, Ar-H5), 5.22 (s, 2H, CH2), 4.00 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.25, 160.01, 148.86, 145.24, 145.15 (t, J = 23.2 Hz), 144.40, 135.27, 134.62, 132.93, 131.28, 128.31, 128.23, 127.65, 126.62, 126.33, 125.37, 123.20, 115.80 (t, J = 3.7 Hz), 109.61 (t, J = 235.4 Hz), 46.17, 39.72. HRMS (ESI): calculated for C21H16ClF2N5O2 [M+Na]+: 446.08528, found: 466.08523.

N-(2-((6,8-dichloro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (6a16), white powder, yield 77%, m.p. 294.1–294.7 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.22 (s, 1H, NH), 8.60 (s, 1H, pyrazol-H5), 8.59 (s, 1H, H2), 8.12 (d, J = 2.4 Hz, 1H, H5), 7.41 (dd, J = 8.1, 1.5 Hz, 1H, H7), 7.34 (td, J = 7.4, 2.0 Hz, 1H, Ar-H2), 7.27–7.20 (m, 3H, CF2H, Ar-H4, Ar-H5) 5.23 (s, 2H, CH2), 4.00 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.29, 159.61, 150.97, 149.19, 147.16, 146.02 (t, J = 23.2 Hz), 144.33, 133.86, 132.30, 131.21, 130.53, 128.41, 128.23, 127.44, 125.02, 124.43, 124.15, 116.16 (t, J = 3.7 Hz), 108.33 (t, J = 235.7 Hz), 55.69, 39.52. HRMS (ESI): calculated for C21H15Cl2F2N5O2 [M+Na]+: 500.04631, found: 500.04620.

N-(2-((6-chloro-8-methyl-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (6a17), white powder, yield 69%, m.p. >310 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.29 (s, 1H, NH), 8.62 (s, 1H, pyrazol-H5), 8.55 (s, 1H, H2), 7.92 (dd, J = 2.6, 0.7 Hz, 1H, H5), 7.76 (dd, J = 2.5, 1.0 Hz, 1H, H7), 7.44 (dd, J = 8.0, 1.2 Hz, 1H, Ar-H2), 7.36–7.31 (m, 1H, Ar-H3),7.27 (t, J = 54.1 Hz, 1H, CF2H), 7.26–7.18 (m, 2H, Ar-H4, Ar-H5), 5.23 (s, 2H, CH2), 3.99 (s, 3H, pyrazol-CH3), 2.51 (s, 3H, 8-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.25, 159.82, 147.45, 145.27, 145.14 (t, J = 23.2 Hz), 138.57, 135.33, 134.54, 133.07, 131.24, 130.98, 128.43, 128.17, 126.73, 126.22, 122.65, 122.57, 115.81 (t, J = 3.4 Hz), 109.60 (t, J = 235.3 Hz), 46.10, 39.73. 16.77. HRMS (ESI): calculated for C22H18ClF2N5O2 [M+Na]+: 480.10093, found:480.10045.

N-(2-((5-bromo-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (6a18), gray powder, yield 69%, m.p. 274.8–276.2 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.17 (s, 1H, NH), 8.55 (s, 1H, pyrazol-H5), 8.52 (s, 1H, H2), 7.78 (dd, J = 6.6, 2.3 Hz, 1H, H6), 7.70–7.62 (m, 2H, H7, H8), 7.47 (dd, J = 7.9, 1.4 Hz, 1H, Ar-H2), 7.38–7.31 (m, 2H, Ar-H3, Ar-H5),7.27 (t, J = 54.1 Hz, 1H, CF2H), 7.24 (td, J = 7.5, 1.4 Hz, 1H, Ar-H4), 5.16 (s, 2H, CH2), 3.99 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.18, 158.72, 150.26, 148.43, 145.13 (t, J = 23.2 Hz), 135.46, 134.68, 133.52, 132.94, 131.07, 128.78, 128.31, 127.61, 126.33, 126.16, 120.15, 119.37, 115.84 (t, J = 3.6 Hz), 109.59 (t, J = 234.7 Hz), 46.21, 39.54. HRMS (ESI): calculated for C21H16BrF2N5O2 [M+Na]+: 510.03476, found: 510.03443.

N-(2-((6-bromo-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (6a19), white powder, yield 41%, m.p. 281.6–282.3 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.13 (s, 1H, NH), 8.51 (s, 1H, pyrazol-H5), 8.50 (s, 1H, H2), 8.23 (d, J = 2.4 Hz, 1H, H5), 7.99 (dd, J = 8.7, 2.4 Hz, 1H, H7), 7.65 (d, J = 8.7 Hz, 1H, H8), 7.44 (dd, J = 8.0, 1.3 Hz, 1H, Ar-H2), 7.35 (td, J = 7.5, 2.0 Hz, 1H, Ar-H3), 7.27 (t, J = 54.1 Hz, 1H, CF2H), 7.26–7.20 (m, 2H, Ar-H4, Ar-H5), 5.21 (s, 2H, CH2), 4.01 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.22, 159.46, 148.50, 146.92, 145.13 (t, J = 23.0 Hz), 144.90, 137.42, 135.30, 132.88, 131.23, 129.67, 128.45, 128.26, 126.65, 126.29, 123.05, 119.77, 115.79(t, J = 3.4 Hz), 109.59(t, J = 235.3 Hz), 46.08, 39.73. HRMS (ESI): calculated for C21H16BrF2N5O2 [M+Na]+: 510.03476, found: 510.03443.

N-(2-((7-bromo-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (6a20), grey powder, yield 67%, m.p. 262.8–263.9 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.14 (s, 1H, NH), 8.50 (s, 1H, pyrazol-H5), 8.49 (s, 1H, H2), 8.05 (dd, J = 8.5, 1.1 Hz, 1H, H5), 7.95–7.87 (m, 1H, H6), 7.75–7.67 (m, 1H, H8), 7.45 (dd, J = 8.0, 1.9 Hz, 1H, Ar-H2), 7.38–7.31 (m, 1H Ar-H3), 7.30–7.12 (m, 3H, CF2H, Ar-H4, Ar-H5), 5.20 (s, 2H, CH2), 4.00 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.22, 160.14, 149.32, 149.05, 145.14 (t, J = 23.2 Hz), 135.31, 132.89, 131.22, 130.30, 129.51, 128.46, 128.26, 128.26, 128.18, 126.59, 126.28, 120.58, 115.85 (d, J = 3.7 Hz), 109.60 (t, J = 234.6 Hz), 46.04, 39.73. HRMS (ESI): calculated for C21H16BrF2N5O2 [M+Na]+: 510.03476, found: 510.03443.

N-(2-((8-bromo-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (6a21), white powder, yield 59%, m.p. 263.7–266.1 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.13 (s, 1H, NH), 8.58 (s, 1H, pyrazol-H5), 8.50 (s, 1H, H2), 8.18–8.13 (m, 2H, H5, H7), 7.49–7.43 (m, 2H, H6, Ar-H2), 7.39–7.31 (m, 1H, Ar-H3), 7.27 (t, J = 54.1 Hz, 1H, CF2H), 7.28–7.20 (m, 2H, Ar-H4, Ar-H5), 5.21 (s, 2H, CH2), 4.00 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.26, 160.00, 148.93, 145.42 (t, J = 23.2 Hz), 145.14, 137.95, 135.27, 132.93, 131.28, 128.30, 128.23, 128.12, 126.61, 126.33, 126.07, 123.10, 121.81, 115.80(t, J = 3.6 Hz), 109.61 (t, J = 234.7 Hz), 46.18, 39.73. HRMS (ESI): calculated for C21H16BrF2N5O2 [M+Na]+: 510.03476, found: 510.03443.

N-(2-((6,8-dibromo-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (6a22), white powder, yield 57%, m.p. >310 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.08 (s, 1H, NH), 8.60 (s, 1H, pyrazol-H5), 8.48 (s, 1H, H2), 8.38 (d, J = 2.2 Hz, 1H, H5), 8.20 (d, J = 2.2 Hz, 1H, H7), 7.41 (dd, J = 8.0, 1.3 Hz, 1H, Ar-H2), 7.35 (ddd, J = 8.0, 6.7, 2.0 Hz, 1H, Ar-H3), 7.27 (t, J = 54.1 Hz, 1H, CF2H), 7.26–7.20 (m, 2H, Ar-H4, Ar-H5), 5.20 (s, 2H, CH2), 4.00 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.24, 158.95, 149.35, 145.12 (t, J = 23.2 Hz), 144.70, 139.68, 135.24, 132.91, 131.22, 128.36, 128.28, 128.15, 126.80, 126.39, 124.05, 123.33, 119.55, 115.72 (t, J = 3.7 Hz), 109.57 (t, J = 235.7 Hz), 46.39, 39.72. HRMS (ESI): calculated for C21H16Br2F2N5O2 [M+Na]+: 587.94528, found: 587.94462.

3-(difluoromethyl)-N-(2-((5-methoxy-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1-methyl-1H-pyrazole-4-carboxamide (6a23), white powder, yield 68%, m.p. 212.9–214.8 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.24 (s, 1H, NH), 8.57 (s, 1H, pyrazol-H5), 8.42 (s, 1H, H2), 7.72 (t, J = 8.2 Hz, 1H, H7), 7.50 (dd, J = 8.0, 1.4 Hz, 1H, Ar-H2), 7.34 (td, J = 7.6, 1.7 Hz, 1H, Ar-H3), 7.30 (t, J = 54.1 Hz, 1H, CF2H), 7.29–7.26 (m, 1H, Ar-H5), 7.24–7.17 (m, 2H, H8, Ar-H4), 7.05 (dd, J = 8.4, 1.0 Hz, 1H, H6), 5.12 (s, 2H, CH2), 4.01 (s, 3H, pyrazol-CH3), 3.85 (s, 3H, 5-CH3O). 13C NMR (100 MHz, DMSO-d6) δ 160.16, 159.71, 158.51, 150.49, 148.22, 145.37 (t, J = 23.2 Hz), 135.44, 135.01, 132.96, 131.14, 128.66, 128.15, 125.99, 124.39, 119.00, 115.92 (t, J = 3.7 Hz), 109.78 (t, J = 235.4 Hz), 56.13, 45.57, 39.72. HRMS (ESI): calculated for C22H19F2N5O3 [M+Na]+: 439.14560, found: 462.13426.

3-(difluoromethyl)-N-(2-((6-methoxy-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1-methyl-1H-pyrazole-4-carboxamide (6a24), white powder, yield 70%, m.p. 259.8–260.2 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.30 (s, 1H, NH), 8.64 (s, 1H, pyrazol-H5), 8.38 (s, 1H, H2), 7.64 (d, J = 8.9 Hz, 1H, H5), 7.52 (d, J = 3.0 Hz, 1H, H8), 7.50–7.43 (m, 2H, H6 Ar-H2), 7.38–7.31 (m, 1H, Ar-H3), 7.30 (t, J = 54.1 Hz, 1H, CF2H), 7.27–7.17 (m, 2H, Ar-H4, Ar-H5), 5.25 (s, 2H, CH2), 4.00 (s, 3H, pyrazol-CH3), 3.86 (s, 3H, 6-CH3O). 13C NMR (100 MHz, DMSO-d6) δ 160.32, 160.22, 158.12, 145.67, 145.15 (t, J = 23.2 Hz), 135.35, 133.07, 131.34, 128.96, 128.40, 128.11, 126.56, 126.13, 124.04, 122.28, 115.89 (t, J = 3.7 Hz), 109.63 (t, J = 235.4 Hz), 106.10, 55.66, 45.84, 39.52. HRMS (ESI): calculated for C22H19F2N5O3 [M+Na]+: 439.14560, found: 462.13426.

3-(difluoromethyl)-N-(2-((7-methoxy-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1-methyl-1H-pyrazole-4-carboxamide (6a25), white powder, yield 69%, m.p. 254.1–276.3 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.43 (s, 1H, NH), 8.70 (s, 1H, pyrazol-H5), 8.50 (s, 1H, H2), 8.07 (d, J = 9.6 Hz, 1H, H5), 7.49 (dd, J = 8.0, 1.3 Hz, 1H, Ar-H2), 7.33 (td, J = 7.5, 1.8 Hz, 1H, Ar-H3), 7.30 (t, J = 54.1 Hz, 1H, CF2H), 7.26 (dd, J = 7.8, 1.7 Hz, 1H, Ar-H5), 7.20 (td, J = 7.5, 1.3 Hz, 1H, Ar-H4), 7.15–7.11 (m, 2H, H6, H8), 5.23 (s, 2H, CH2), 4.00 (s, 3H, pyrazol-CH3), 3.89 (s, 3H, 7-CH3O). 13C NMR (100 MHz, DMSO-d6) δ 164.15, 160.20, 160.18, 150.26, 148.52, 145.16 (t, J = 23.2 Hz), 135.41, 133.09, 131.18, 128.55, 128.11, 127.85, 126.42, 126.01, 116.86, 115.93 (t, J = 3.7 Hz), 114.80, 109.64 (t, J = 235.4 Hz), 108.29, 55.82, 45.66, 39.52. HRMS (ESI): calculated for C22H19F2N5O3 [M+Na]+: 439.14560, found: 462.13426.

3-(difluoromethyl)-N-(2-((8-methoxy-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1-methyl-1H-pyrazole-4-carboxamide (6a26), white powder, yield 70%, m.p. 268.8–270.4 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.22 (s, 1H, NH), 8.54 (s, 1H, pyrazol-H5), 8.44 (s, 1H, H2), 7.71 (dd, J = 8.0, 1.3 Hz, 1H, H5), 7.52–7.43 (m, 2H, H6, Ar-H2), 7.41–7.32 (m, 2H, H7, Ar-H3), 7.31 (t, J = 54.1 Hz, 1H, CF2H), 7.29–7.17 (m, 2H, Ar-H4, Ar-H5), 5.22 (s, 2H, CH2), 4.01 (s, 3H, pyrazol-CH3), 3.90 (s, 3H, 8-CH3O). 13C NMR (100 MHz, DMSO-d6) δ 160.51, 160.17, 154.53, 146.49, 145.16 (t, J = 23.2 Hz), 138.45, 135.33, 132.90, 131.14, 128.35, 128.18, 127.68, 126.34, 126.14, 122.46, 117.07, 115.89 (t, J = 3.7 Hz), 115.08, 109.65 (t, J = 235.4 Hz), 56.01, 45.82, 39.52. HRMS (ESI): calculated for C22H19F2N5O3 [M+Na]+: 439.14560, found: 462.13426.HRMS (ESI): calculated for C22H19F2N5O3 [M+Na]+: 439.14560, found: 462.13426.

3-(difluoromethyl)-N-(2-((6,7-dimethoxy-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1-methyl-1H-pyrazole-4-carboxamide (6a27), white powder, yield 77%, m.p. 290.3–292.5 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.26 (s, 1H, NH), 8.55 (s, 1H, pyrazol-H5), 8.41 (s, 1H, H2), 7.51 (dd, J = 8.0, 1.3 Hz, 1H, Ar-H2), 7.46 (s, 1H, H5), 7.34 (td, J = 7.6, 1.8 Hz, 1H, Ar-H3), 7.31 (t, J = 54.1 Hz, 1H, CF2H), 7.26 (dd, J = 7.8, 1.8 Hz, 1H, Ar-H5), 7.21 (ddd, J = 7.8, 7.1, 1.3 Hz, 1H, Ar-H4), 7.16 (s, 1H, H8), 5.21 (s, 2H, CH2), 4.01 (s, 3H, pyrazol-CH3), 3.91 (s, 3H, 7-CH3O), 3.87 (s, 3H, 6-CH3O). 13C NMR (100 MHz, DMSO-d6) δ 160.13, 159.94, 154.80, 149.00, 146.37, 145.15 (t, J = 23.2 Hz), 144.22, 135.36, 132.90, 131.05, 128.54, 128.20, 126.17, 126.03, 115.95 (t, J = 3.7 Hz), 114.40, 109.64 (t, J = 235.7 Hz), 107.92, 105.12, 56.05, 55.76, 45.68, 39.72. HRMS (ESI): calculated for C23H21F2N5O4 [M+Na]+: 492.14538, found: 492.14539.

3-(difluoromethyl)-1-methyl-N-(2-((5-nitro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1H-pyrazole-4-carboxamide (6a28), white powder, yield 75%, m.p. 278.1–279.2 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.09 (s, 1H, NH), 8.61 (s, 1H, H2), 8.43 (s, 1H, pyrazol-H5), 8.02–7.98 (m, 1H, H6), 7.94–7.91 (m, 1H, H8), 7.83–7.79 (m, 1H, H7), 7.46 (dd, J = 7.9, 1.3 Hz, 1H, Ar-H2), 7.39–7.32 (m, 2H, Ar-H3, Ar-H5), 7.27 (t, J = 54.1 Hz, 1H, CF2H), 7.24 (td, J = 7.5, 1.4 Hz, 1H, Ar-H4), 5.18 (s, 2H, CH2), 4.01 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.24, 157.45, 157.18, 149.69, 148.15, 145.15(t, J = 23.2 Hz), 135.50, 134.99, 132.91, 130.75, 130.15, 130.04, 128.92, 128.48, 126.42, 126.24, 120.99, 115.76(t, J = 3.6 Hz), 109.58 (t, J = 234.7 Hz), 46.17, 39.47. HRMS (ESI): calculated for C21H16F2N6O4 [M+Na]+: 477.10933, found: 477.10936.

3-(difluoromethyl)-1-methyl-N-(2-((6-nitro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1H-pyrazole-4-carboxamide (6a29), light yellow powder, yield 64%, m.p. 233.9–234.7 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.07 (s, 1H, NH), 8.77 (d, J = 2.7 Hz, 1H, H5), 8.63 (s, 1H, pyrazol-H5), 8.55 (dd, J = 9.0, 2.7 Hz, 1H, H7), 8.49 (s, 1H, H2), 7.88 (d, J = 9.0 Hz, 1H, H8), 7.40 (dd, J = 7.9, 1.6 Hz, 1H, Ar-H2), 7.36 (td, J = 7.2, 1.8 Hz, 1H, Ar-H3), 7.31–7.27 (m, 1H, Ar-H5), 7.27 (t, J = 54.1 Hz, 1H, CF2H), 7.27–7.22 (m, 1H, Ar-H4), 5.25 (s, 2H, CH2), 4.00 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.29, 159.73, 151.97, 151.22, 145.31, 145.11 (t, J = 23.2 Hz), 135.28, 132.92, 131.45, 129.15, 128.45, 128.39, 128.33, 127.07, 126.48, 122.22, 121.64, 115.68 (t, J = 3.7 Hz), 109.53 (t, J = 235.7 Hz), 46.35, 39.52. HRMS (ESI): calculated for C21H16F2N6O4 [M+Na]+: 477.10933, found: 477.10936.

3-(difluoromethyl)-1-methyl-N-(2-((7-nitro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1H-pyrazole-4-carboxamide (6a30), orange powder, yield 61%, m.p. 253.8–256.1 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.09 (s, 1H, NH), 8.60 (s, 1H, pyrazol-H5), 8.48 (s, 1H, H2), 8.41 (d, J = 2.2 Hz, 1H, H8), 8.34 (dd, J = 8.8, 0.5 Hz, 1H, H5), 8.26 (dd, J = 8.8, 2.3 Hz, 1H, H6), 7.41 (dd, J = 7.9, 1.4 Hz, 1H, Ar-H2), 7.36 (td, J = 7.4, 1.9 Hz, 1H, Ar-H3), 7.28 (dd, J = 7.8, 1.9 Hz, 1H, Ar-H5), 7.26–7.21 (m, 2H, CF2H, Ar-H4), 5.23 (s, 2H, CH2), 4.00 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.29, 159.59, 151.14, 150.16, 148.27, 145.12 (t, J = 23.2 Hz), 135.30, 132.91, 131.35, 128.53, 128.43, 128.31, 126.88, 126.42, 125.81, 122.33, 120.83, 115.78 (t, J = 3.7 Hz), 109.57 (t, J = 235.7 Hz), 46.35, 39.72. HRMS (ESI): calculated for C21H16F2N6O4 [M+Na]+: 477.10933, found: 477.10936.

3-(difluoromethyl)-1-methyl-N-(2-((8-nitro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1H-pyrazole-4-carboxamide (6a31), yellow powder, yield 60%, m.p. 226.8–208.0 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.09 (s, 1H, NH), 8.59 (s, 1H, pyrazol-H5), 8.48 (s, 1H, H2), 8.36 (d, J = 8.0 Hz, 1H, H5), 8.33 (d, J = 7.9 Hz, 1H, H7), 7.69 (t, J = 7.9 Hz, 1H, H6), 7.46–7.38 (m, 1H, Ar-H2), 7.37–7.32 (m, 1H, Ar-H3), 7.31–7.20 (m, 3H, CF2H, Ar-H4, Ar-H5), 5.22 (s, 2H, CH2), 4.00 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.29, 159.13, 150.56, 146.48, 145.14 (t, J = 23.2 Hz), 139.66, 135.26, 132.95, 131.35, 129.96, 128.39, 128.28, 127.98, 126.94, 126.83, 126.44, 122.96, 115.74 (t, J = 3.7 Hz), 109.59 (t, J = 235.7 Hz), 46.43, 39.52. HRMS (ESI): calculated for C21H16F2N6O4 [M+Na]+: 477.10933, found: 477.10936.

3-(difluoromethyl)-N-(2-((6-iodo-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1-methyl-1H-pyrazole-4-carboxamide (6a32), white powder, yield 74%, m.p. 261.8–263.1 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.12 (s, 1H, NH), 8.49 (s, 1H, pyrazol-H5), 8.49 (s, 1H, H2), 8.41 (d, J = 2.1 Hz, 1H, H5), 8.14–8.07 (m, 1H, H7), 7.50–7.44 (m, 2H, H8, Ar-H2), 7.39–7.30 (m, 1H, Ar-H3), 7.27 (t, J = 54.1 Hz, 1H, CF2H), 7.26–7.19 (m, 2H, Ar-H5, Ar-H5), 5.20 (s, 2H, CH2), 4.01 (s, 3H, pyrazol-CH3). 13C NMR (100 MHz, DMSO-d6) δ 160.21, 159.26, 148.53, 147.19, 145.13(t, J = 23.2 Hz), 142.92, 135.27, 134.40, 132.88, 131.27, 129.40, 128.39, 128.24, 126.65, 126.29, 123.20, 115.80 (t, J = 3.7 Hz), 109.59 (t, J = 235.7 Hz), 92.48, 46.06, 39.73. HRMS (ESI): calculated for C21H16F2IN5O2 [M+Na]+: 558.02090, found: 558.02095.