3.9. General Synthesis Procedure for Target Compounds 1–30

Compounds 1–30 were synthesized according to [20,21]. Substituted benzamide (5.0 mmol) and 1,2-dichloroethane (10 mL) were added to a 100 mL three-necked flask under N₂. The reaction mixture was cooled to 0 °C and oxalyl chloride (1.27 g, 10.0 mmol) was added dropwise under stirring, then the mixture was stirred at room temperature for 1 h, left standing at 60 ° C for 3 h and refluxed for 1 h. The solvent and excess oxalyl chloride were evaporated under reduced pressure to give a yellow transparent liquid. Anhydrous dichloromethane (5 mL) was added to the residue, then a substituted 2-aminopyrimidine (2.5 mmol) was added to the system and reacted at room temperature for 12 h. The solvent was removed under reduced pressure and the residue was purified by flash column chromatography on silica gel to give compounds 1–30.

N-((4,6-bis(2,2,2-Trifluoroethoxy)pyrimidin-2-yl)carbamoyl)-2,6-difluorobenzamide (1). White solid, mp 163–164 °C, yield = 83%. ¹H-NMR (DMSO-d₆) δ 11.65 (s, 1H, NH), 10.77 (s, 1H, NH), 7.76–7.57 (m, 1H, Ph), 7.26 (t, J = 8.3 Hz, 2H, Ph), 6.40 (s, 1H, ArH), 5.07 (q, J = 8.9 Hz, 4H, OCH₂CF₃). ¹³C-NMR (DMSO-d₆) δ 170.9, 160.6, 156.3, 148.9, 134.2, 125.6, 123.4, 113.2, 113.0, 86.8, 63.7, 63.4, 63.1, 62.8. HRMS (ESI): m/z calcd for C₁₆H₁₀F₈N₄O₄ [M + H]⁺: 475.0652, found 475.0641.

N-((4,6-bis(2,2,2-Trifluoroethoxy)pyrimidin-2-yl)carbamoyl)-2-chlorobenzamide (2). White solid, mp 173–175 °C, yield = 95%. ¹H-NMR (DMSO-d₆) δ 11.47 (s, 1H, NH), 10.96 (s, 1H, NH), 7.65 (dd, J = 7.6, 1.6 Hz, 1H, Ph), 7.61–7.52 (m, 2H, Ph), 7.48 (td, J = 7.3, 1.7 Hz, 1H, Ph), 6.39 (s, 1H, ArH), 5.07 (q, J = 8.9 Hz, 4H, OCH₂CF₃). ¹³C-NMR (DMSO-d₆) δ 170.9, 169.2, 156.3, 149.0, 135.6, 133.1, 130.7, 130.0, 128.2, 125.7, 123.4, 86.8, 63.6, 63.3, 63.0, 62.8. HRMS (ESI): m/z calcd for C₁₆H₁₁ClF₆N₄O₄ [M + H]⁺: 473.0451, found 473.0440.

N-((4,6-bis(2,2,2-Trifluoroethoxy)pyrimidin-2-yl)carbamoyl)-2-bromobenzamide (3). White solid, mp 110–112 °C, yield = 77%. ¹H-NMR (DMSO-d₆) δ 11.46 (s, 1H, NH), 10.96 (s, 1H, NH), 7.73 (d, J = 7.9 Hz, 1H, Ph), 7.62 (dd, J = 7.4, 1.7 Hz, 1H, Ph), 7.57–7.42 (m, 2H, Ph), 6.39 (s, 1H, ArH), 5.07 (q, J = 8.9 Hz, 4H, OCH₂CF₃). ¹³C-NMR (DMSO-d₆) δ 170.8, 170.0, 156.2, 149.0, 137.8, 133.7, 133.0, 129.8, 128.6, 125.6, 119.5, 86.8, 63.6, 63.3, 63.0, 62.7. HRMS (ESI): m/z calcd for C₁₆H₁₁BrF₆N₄O₄ [M + Na]⁺: 538.9766, found 538.9769.

N-((4,6-bis(2,2,2-Trifluoroethoxy)pyrimidin-2-yl)carbamoyl)-2-iodobenzamide (4). White solid, mp 115–116 °C, yield = 88%. ¹H-NMR (DMSO-d₆) δ 11.42 (s, 1H, NH), 11.01 (s, 1H, NH), 7.95 (dd, J = 7.9, 1.0 Hz, 1H, Ph), 7.72–7.38 (m, 2H, Ph), 7.28 (td, J = 7.6, 1.9 Hz, 1H, Ph), 6.39 (s, 1H, ArH), 5.07 (q, J = 8.9 Hz, 4H, OCH₂CF₃). ¹³C-NMR (DMSO-d₆) δ 171.7, 170.9, 156.3, 149.1, 141.7, 140.2, 132.9, 129.2, 129.1, 125.7, 125.4, 93.9, 86.8, 63.6, 63.4, 63.1, 62.8. HRMS (ESI): m/z calcd for C₁₆H₁₁F₆IN₄O₄ [M + Na]⁺: 586.9627, found 586.9603.

N-((4,6-bis(2,2,2-Trifluoroethoxy)pyrimidin-2-yl)carbamoyl)-4-chlorobenzamide (5). White solid, mp 162–163 °C, yield = 94%. ¹H-NMR (DMSO-d₆) δ 11.42 (s, 1H, NH), 11.22 (s, 1H, NH), 8.02 (d, J = 8.5 Hz, 2H, Ph), 7.60 (d, J = 8.6 Hz, 2H, Ph), 6.36 (s, 1H, ArH), 5.07 (q, J = 8.9 Hz, 4H, OCH₂CF₃). ¹³C-NMR (DMSO-d₆) δ 170.8, 168.0, 156.4, 149.4, 139.1, 132.1, 131.1, 129.6, 125.6, 86.4, 63.6, 63.3, 63.0, 62.8. HRMS (ESI): m/z calcd for C₁₆H₁₁ClF₆N₄O₄ [M + H]⁺: 473.0451, found 473.0442.

N-((4,6-bis(2,2,2-Trifluoroethoxy)pyrimidin-2-yl)carbamoyl)-2-(trifluoromethyl)benzamide (6). White solid, mp 51–53 °C, yield = 68%. ¹H-NMR (DMSO-d₆) δ 11.55 (s, 1H, NH), 10.91 (s, 1H, NH), 7.88 (d, J = 7.7 Hz, 1H, Ph), 7.85–7.71 (m, 3H, Ph), 6.40 (s, 1H, ArH), 5.07 (q, J = 8.9 Hz, 4H, OCH₂CF₃). ¹³C-NMR (DMSO-d₆) δ 170.8, 170.0, 156.3, 149.0, 134.8, 133.5, 131.9, 129.3, 127.4, 127.1, 126.8, 126.5, 126.3, 125.6, 123.4, 86.7, 63.6, 63.3, 63.0, 62.8. HRMS (ESI): m/z calcd for C₁₇H₁₁F₉N₄O₄ [M + H]⁺: 507.0715, found 507.0711.

N-((4,6-bis(2,2,2-Trifluoroethoxy)pyrimidin-2-yl)carbamoyl)-4-(trifluoromethyl)benzamide (7). White solid, mp 167–169 °C, yield = 93%. ¹H-NMR (DMSO-d₆) δ 11.61 (s, 1H, NH), 11.15 (s, 1H, NH), 8.17 (d, J = 8.1 Hz, 2H, Ph), 7.90 (d, J = 8.1 Hz, 2H, Ph), 6.38 (s, 1H, ArH), 5.07 (q, J = 8.9 Hz, 4H, OCH₂CF₃). ¹³C-NMR (DMSO-d₆) δ 170.9, 167.9, 156.4, 149.3, 137.4, 133.7, 133.5, 130.1, 126.5, 126.5, 125.8, 125.6, 86.5, 63.7, 63.4, 63.1, 62.8. HRMS (ESI): m/z calcd for C₁₇H₁₁F₉N₄O₄ [M + H]⁺: 507.0715, found 507.0713.

N-((4,6-bis(2,2,2-Trifluoroethoxy)pyrimidin-2-yl)carbamoyl)-5-chloro-2-methoxybenzamide (8). White solid, mp 164–166 °C, yield = 95%. ¹H-NMR (DMSO-d₆) δ 11.04 (s, 1H, NH), 10.98 (s, 1H, NH), 7.65 (d, J = 2.7 Hz, 1H, Ph), 7.61 (dd, J = 8.9, 2.8 Hz, 1H, Ph), 7.23 (d, J = 8.9 Hz, 1H, Ph), 6.39 (s, 1H, ArH), 5.06 (q, J = 8.9 Hz, 4H, OCH₂CF₃), 3.89 (s, 3H, CH₃). ¹³C-NMR (DMSO-d₆) δ 170.9, 167.3, 156.6, 156.3, 148.9, 133.9, 130.1, 125.4, 125.1, 115.3, 86.7, 63.5, 63.3, 63.0, 62.7, 57.5. HRMS (ESI): m/z calcd for C₁₇H₁₃ClF₆N₄O₅ [M + H]⁺: 503.0557, found 503.0535.

N-((4,6-bis(2,2,2-Trifluoroethoxy)pyrimidin-2-yl)carbamoyl)-2,4-dichlorobenzamide (9). White solid, mp 109–110 °C, yield = 92%. ¹H-NMR (DMSO-d₆) δ 11.49 (s, 1H, NH), 10.88 (s, 1H, NH), 7.79 (d, J = 1.9 Hz, 1H, Ph), 7.68 (d, J = 8.2 Hz, 1H, Ph), 7.58 (dd, J = 8.2, 2.0 Hz, 1H, Ph), 6.40 (s, 1H, ArH), 5.06 (q, J = 8.9 Hz, 4H, OCH₂CF₃). ¹³C-NMR (DMSO-d₆) δ 170.8, 168.3, 156.3, 149.0, 136.9, 134.6, 132.0, 131.4, 130.3, 128.5, 125.6, 86.8, 63.6, 63.3, 63.0. HRMS (ESI): m/z calcd for C₁₆H₁₀Cl₂F₆N₄O₄ [M + Na]⁺: 528.9881, found 528.9866.

N-((4,6-bis(2,2,2-Trifluoroethoxy)pyrimidin-2-yl)carbamoyl)-2,6-dichlorobenzamide (10). White solid, mp 62–64 °C, yield = 81%. ¹H-NMR (DMSO-d₆) δ 11.68 (s, 1H, NH), 10.80 (s, 1H, NH), 7.82–7.39 (m, 3H, Ph), 6.41 (s, 1H, ArH), 5.08 (q, J = 8.9 Hz, 4H, OCH₂CF₃). ¹³C-NMR (DMSO-d₆) δ 170.9, 156.2, 148.8, 131.4, 129.2, 127.8, 125.6, 123.4, 121.2, 100.5, 86.9, 63.7, 63.4, 63.1, 62.9. HRMS (ESI): m/z calcd for C₁₆H₁₀Cl₂F₆N₄O₄ [M + Na]⁺: 528.9881, found 528.9866.

2-Chloro-N-((4,6-dimethylpyrimidin-2-yl)carbamoyl)benzamide (11). White solid, mp 186–188 °C, yield = 87%. ¹H-NMR (DMSO-d₆) δ 12.51 (s, 1H, NH), 10.61 (s, 1H, NH), 7.64 (dd, J = 7.6, 1.6 Hz, 1H, Ph), 7.61–7.52 (m, 2H, Ph), 7.47 (td, J = 7.3, 1.5 Hz, 1H, Ph), 6.98 (s, 1H, ArH), 2.33 (s, 6H, Ar-CH₃). ¹³C-NMR (DMSO-d₆) δ 168.8, 167.5, 157.6, 149.8, 136.3, 132.9, 130.8, 130.6, 129.8, 128.3, 116.0, 24.2. HRMS (ESI): m/z calcd for C₁₄H₁₃ClN₄O₂ [M + Na]⁺: 327.0625, found 327.0629.

2-Chloro-N-((4,6-dimethoxypyrimidin-2-yl)carbamoyl)benzamide (12). White solid, mp 155–157 °C, yield = 89%. ¹H-NMR (DMSO-d₆) δ 11.87 (s, 1H, NH), 10.67 (s, 1H, NH), 7.62 (dd, J = 7.6, 1.6 Hz, 1H, Ph), 7.59–7.50 (m, 2H, Ph), 7.46 (td, J = 7.3, 1.5 Hz, 1H, Ph), 5.97 (s, 1H, ArH), 3.82 (s, 6H, Ar-OCH₃). ¹³C-NMR (DMSO-d₆) δ 172.4, 168.4, 156.9, 149.4, 136.3, 132.8, 130.6, 130.5, 129.7, 128.3, 85.1, 55.2. HRMS (ESI): m/z calcd for C₁₄H₁₃ClN₄O₄ [M + Na]⁺: 359.0523, found 359.0524.

2-Chloro-N-((4,6-diethoxypyrimidin-2-yl)carbamoyl)benzamide (13). White solid, mp 113–115 °C, yield = 91%. ¹H-NMR (DMSO-d₆) δ 11.92 (s, 1H, NH), 10.61 (s, 1H, NH), 7.65 (dd, J = 7.6, 1.5 Hz, 1H, Ph), 7.57 (qd, J = 8.1, 4.1 Hz, 2H, Ph), 7.52–7.44 (m, 1H, Ph), 5.87 (s, 1H, ArH), 4.20 (q, J = 7.0 Hz, 4H, OCH₂CH₃), 1.26 (t, J = 7.1 Hz, 6H, OCH₂CH₃). ¹³C-NMR (DMSO-d₆) δ 171.9, 167.9, 156.9, 149.4, 136.3, 135.8, 132.8, 130.6, 129.7, 128.3, 85.3, 64.5, 63.6, 15.2, 15.0. HRMS (ESI): m/z calcd for C₁₆H₁₇ClN₄O₄ [M + Na]⁺: 387.0836, found 387.0851.

2-Chloro-N-((4,6-dichloropyrimidin-2-yl)carbamoyl)benzamide (14). White solid, mp 156–158 °C, yield = 88%. ¹H-NMR (DMSO-d₆) δ 11.52 (s, 1H, NH), 11.24 (s, 1H, NH), 7.69 (s, 1H, ArH), 7.65 (dd, J = 7.6, 1.5 Hz, 1H, Ph), 7.57 (qd, J = 8.1, 1.7 Hz, 2H, Ph), 7.49 (td, J = 7.2, 1.9 Hz, 1H, Ph). ¹³C-NMR (DMSO-d₆) δ 169.0, 162.5, 157.4, 148.8, 133.1, 130.8, 130.8, 130.0, 128.3, 117.0. HRMS (ESI): m/z calcd for C₁₂H₇Cl₃N₄O₂ [M + Na]⁺: 366.9532, found 366.9549.

2-Chloro-N-((4-chloro-6-methylpyrimidin-2-yl)carbamoyl)benzamide (15). White solid, mp 126–128 °C, yield = 93%. ¹H-NMR (DMSO-d₆) δ 11.89 (s, 1H, NH), 10.98 (s, 1H, NH), 7.65 (dd, J = 7.6, 1.6 Hz, 1H, Ph), 7.63–7.51 (m, 2H, Ph), 7.47 (td, J = 7.3, 1.5 Hz, 1H, Ph), 7.32 (s, 1H, ArH), 2.40 (s, 3H, CH₃). ¹³C-NMR (DMSO-d₆) δ 171.4, 169.1, 168.3, 161.4, 157.5, 149.2, 138.1, 131.5, 130.5, 129.6, 127.9, 116.4, 24.2. HRMS (ESI): m/z calcd for C₁₃H₁₀Cl₂N₄O₂ [M + Na]⁺: 347.0079, found 347.0064.

2-Chloro-N-((4-chloro-6-methoxypyrimidin-2-yl)carbamoyl)benzamide (16). White solid, mp 166–167 °C, yield = 87%. ¹H-NMR (DMSO-d₆) δ 11.64 (s, 1H, NH), 10.98 (s, 1H, NH), 7.65 (d, J = 7.5 Hz, 1H, Ph), 7.56 (d, J = 8.5 Hz, 2H, Ph), 7.48 (t, J = 7.3 Hz, 1H, Ph), 6.82 (s, 1H, ArH), 3.91 (s, 3H, OCH₃). ¹³C-NMR (DMSO-d₆) δ 171.9, 168.6, 160.8, 157.2, 149.0, 135.7, 132.9, 130.6, 129.9, 128.2, 102.6, 55.7. HRMS (ESI): m/z calcd for C₁₃H₁₀Cl₂N₄O₃ [M + Na]⁺: 363.0028, found 363.0013.

2-Chloro-N-((4-chloro-6-(2,2,2-trifluoroethoxy)pyrimidin-2-yl)carbamoyl)benzamide (17). White solid, mp 144–146 °C, yield = 88%. ¹H-NMR (DMSO-d₆) δ 11.51 (s, 1H, NH), 11.07 (s, 1H, NH), 7.65 (dd, J = 7.5, 1.5 Hz, 1H, Ph), 7.62–7.51 (m, 2H, Ph), 7.48 (td, J = 7.3, 1.7 Hz, 1H, Ph), 7.09 (s, 1H, ArH), 5.10 (q, J = 8.8 Hz, 2H, OCH₂CF₃). ¹³C-NMR (DMSO-d₆) δ 170.0, 169.1, 161.8, 156.9, 148.9, 135.6, 133.1, 130.8, 130.0, 128.2, 125.5, 123.3, 103.0, 63.8, 63.5, 63.2, 62.9. HRMS (ESI): m/z calcd for C₁₄H₉Cl₂F₃N₄O₃ [M + Na]⁺: 430.9901, found 430.9887.

2-Chloro-N-((4-chloro-6-morpholinopyrimidin-2-yl)carbamoyl)benzamide (18). White solid, mp 147–149 °C, yield = 85%. ¹H-NMR (DMSO-d₆) δ 11.78 (s, 1H, NH), 10.59 (s, 1H, NH), 7.62 (dd, J = 7.6, 1.6 Hz, 1H, Ph), 7.59–7.50 (m, 2H, Ph), 7.46 (td, J = 7.3, 1.5 Hz, 1H, Ph), 6.71 (s, 1H, ArH), 3.58 (dd, J = 23.7, 4.9 Hz, 8H, morpholine). ¹³C-NMR (DMSO-d₆) δ 168.2, 163.6, 157.0, 149.3, 136.1, 132.9, 130.7, 130.6, 129.8, 128.3, 97.9, 66.6, 60.7. HRMS (ESI): m/z calcd for C₁₆H₁₅Cl₂N₅O₃ [M + Na]⁺: 418.0450, found 418.0441.

2-Chloro-N-((4-chloro-6-(diethylamino)pyrimidin-2-yl)carbamoyl)benzamide (19). white solid, mp 151–153 °C, yield = 83%. ¹H-NMR (DMSO-d₆) δ 11.97 (s, 1H, NH), 10.46 (s, 1H, NH), 7.60 (dd, J = 7.6, 1.6 Hz, 1H, Ph), 7.58–7.49 (m, 2H, Ph), 7.45 (td, J = 7.3, 1.6 Hz, 1H, Ph), 6.49 (s, 1H, ArH), 3.44 (s, 4H, CH₂CH₃), 1.19–0.91 (m, 6H, CH₂CH₃). ¹³C-NMR (DMSO-d₆) δ 168.1, 162.1, 159.4, 157.2, 149.6, 136.5, 132.7, 130.5, 130.5, 129.7, 128.3, 97.1, 43.3, 13.4. HRMS (ESI): m/z calcd for C₁₆H₁₇Cl₂N₅O₂ [M + Na]⁺: 404.0657, found 404.0642.

2-Chloro-N-((4-methyl-6-(2,2,2-trifluoroethoxy)pyrimidin-2-yl)carbamoyl)benzamide (20). White solid, mp 56–58 °C, yield = 82%. ¹H-NMR (DMSO-d₆) δ 12.13 (s, 1H, NH), 10.79 (s, 1H, NH), 7.72–7.63 (m, 1H, Ph), 7.63–7.52 (m, 2H, Ph), 7.49 (td, J = 7.3, 1.6 Hz, 1H, Ph), 6.71 (s, 1H, ArH), 5.07 (q, J = 8.9 Hz, 2H, OCH₂CF₃), 2.34 (s, 3H, CH₃). ¹³C-NMR (DMSO-d₆) δ 171.4, 170.3, 169.3, 168.1, 161.4, 157.0, 149.4, 136.0, 132.9, 130.7, 129.9, 128.2, 102.1, 62.8, 62.5, 62.2, 61.9, 24.1. HRMS (ESI): m/z calcd for C₁₅H₁₂ClF₃N₄O₃ [M + Na]⁺: 411.0448, found 411.0442.

2-Chloro-N-((4-(pyrrolidin-1-yl)-6-(2,2,2-trifluoroethoxy)pyrimidin-2-yl)carbamoyl)benzamide (21). White solid, mp 121–122 °C, yield = 81%. ¹H-NMR (DMSO-d₆) δ 12.55 (s, 1H, NH), 10.28 (s, 1H, NH), 7.61 (d, J = 7.4 Hz, 1H, Ph), 7.58–7.50 (m, 2H, Ph), 7.46 (td, J = 7.3, 1.7 Hz, 1H, Ph), 5.62 (s, 1H, ArH), 4.97 (q, J = 9.0 Hz, 2H, OCH₂CF₃), 3.25 (s, 2H, tetrahydropyrrole), 3.02 (s, 2H, tetrahydropyrrole), 1.97–1.82 (m, 2H, tetrahydropyrrole), 1.77–1.60 (m, 2H, tetrahydropyrrole). ¹³C-NMR (DMSO-d₆) δ 168.7, 167.3, 161.8, 156.7, 149.8, 136.9, 132.5, 130.5, 130.3, 129.4, 128.3, 125.9, 81.1, 62.2, 61.9, 61.6, 47.3, 25.7. HRMS (ESI): m/z calcd for C₁₈H₁₇ClF₃N₅O₃ [M + H]⁺: 444.1050, found 444.1047.

2-Chloro-N-((4-(hexylamino)-6-(2,2,2-trifluoroethoxy)pyrimidin-2-yl)carbamoyl)benzamide (22). White solid, mp 126–128 °C, yield = 83%. ¹H-NMR (DMSO-d₆) δ 12.40 (s, 1H, NH), 10.28 (s, 1H, NH), 7.85–7.36 (m, 5H, Ph), 5.62 (s, 1H, ArH), 4.93 (q, J = 9.0 Hz, 2H, OCH₂CF₃), 3.05 (s, 2H, N–CH₂(CH₂)₄CH₃), 1.46–1.07 (m, 8H, N–CH₂(CH₂)₄CH₃), 0.86 (t, J = 6.8 Hz, 3H, N(CH₂)₅CH₃). ¹³C-NMR (DMSO-d₆) δ 168.0, 165.1, 157.1, 151.8, 149.8, 136.7, 132.6, 130.5, 129.6, 128.3, 125.9, 123.6, 82.2, 62.1, 61.8, 41.3, 32.0, 29.6, 27.0, 23.1, 14.9. HRMS (ESI): m/z calcd for C₂₀H₂₃ClF₃N₅O₃ [M + Na]⁺: 496.1339, found 496.1357.

2,4-Dichloro-N-((4,6-dimethylpyrimidin-2-yl)carbamoyl)benzamide (23). White solid, mp 185–186 °C, yield = 81%. ¹H-NMR (DMSO-d₆) δ 12.50 (s, 1H, NH), 10.60 (s, 1H, NH), 7.77 (d, J = 2.0 Hz, 1H, Ph), 7.67 (d, J = 8.2 Hz, 1H, Ph), 7.57 (dd, J = 8.2, 2.0 Hz, 1H, Ph), 6.99 (d, J = 2.7 Hz, 1H, ArH), 2.35 (s, 6H, CH₃). ¹³C-NMR (DMSO-d₆) δ 168.8, 167.0, 157.6, 149.8, 136.5, 135.4, 131.8, 131.1, 130.3, 128.5, 116.1, 24.3. HRMS (ESI): m/z calcd for C₁₄H₁₂Cl₂N₄O₂ [M + Na]⁺: 361.0235, found 361.0208.

2,4-Dichloro-N-((4-methyl-6-(2,2,2-trifluoroethoxy)pyrimidin-2-yl)carbamoyl)benzamide (24). White solid, mp 155–157 °C, yield = 81%. ¹H-NMR (DMSO-d₆) δ 12.14 (s, 1H, NH), 10.77 (s, 1H, NH), 7.76 (d, J = 2.0 Hz, 1H, Ph), 7.70 (d, J = 8.3 Hz, 1H, Ph), 7.64–7.54 (m, 1H, Ph), 6.71 (s, 1H, ArH), 5.07 (q, J = 8.9 Hz, 2H, OCH₂CF₃), 2.37 (s, 3H, CH₃). ¹³C-NMR (DMSO-d₆) δ 170.4, 169.3, 167.5, 157.1, 149.5, 136.7, 135.0, 132.0, 131.2, 130.3, 128.5, 125.7, 102.2, 62.9, 62.6, 62.3, 62.0, 24.2. HRMS (ESI): m/z calcd for C₁₅H₁₁Cl₂F₃N₄O₃ [M + Na]⁺: 445.0058, found 445.0064.

2,6-Dichloro-N-((4-chloro-6-(2,2,2-trifluoroethoxy)pyrimidin-2-yl)carbamoyl)benzamide (25). White solid, mp 125–126 °C, yield = 87%. ¹H-NMR (-DMSO-d₆) δ 11.64 (s, 1H, NH), 10.90 (s, 1H, NH), 7.59 (d, J = 8.9 Hz, 2H, Ph), 7.56–7.48 (m, 1H, Ph), 7.12 (s, 1H, ArH), 5.11 (q, J = 8.9 Hz, 2H, OCH₂CF₃). ¹³C-NMR (DMSO-d₆) δ 170.0, 165.0, 161.8, 156.8, 148.7, 137.7, 132.1, 131.9, 129.0, 125.4, 103.2, 63.6, 63.3, 63.0. HRMS (ESI): m/z calcd for C₁₄H₈Cl₃F₃N₄O₃ [M + Na]⁺: 464.9512, found 464.9502.

2,6-Dichloro-N-((4-chloro-6-(diethylamino)pyrimidin-2-yl)carbamoyl)benzamide (26). White solid, mp 169–171 °C, yield = 81%. ¹H-NMR (DMSO-d₆) δ 12.42 (s, 1H, NH), 10.44 (s, 1H, NH), 7.61–7.47 (m, 3H, Ph), 6.54 (s, 1H, ArH), 3.46 (s, 4H, CH₂CH₃), 1.12 (s, 6H, CH₂CH₃). ¹³C-NMR (DMSO-d₆) δ 165.0, 164.0, 160.9, 158.5, 136.7, 131.1, 130.9, 128.1, 96.2, 42.6, 25.8, 12.4. HRMS (ESI): m/z calcd for C₁₆H₁₆Cl₃N₅O₂ [M + H]⁺: 416.0448, found 416.0444.

2,6-Dichloro-N-((4-(diethylamino)-6-(2,2,2-trifluoroethoxy)pyrimidin-2-yl)carbamoyl)benzamide (27). White solid, mp 140–142 °C, yield = 87%. ¹H-NMR (DMSO-d₆) δ 12.84 (s, 1H, NH), 10.22 (s, 1H, NH), 8.60–6.40 (m, 3H, Ph), 5.84 (s, 1H, ArH), 4.96 (q, J = 9.0 Hz, 2H, OCH₂CF₃), 3.46 (s, 4H, CH₂CH₃), 1.12 (s, 6H, CH₂CH₃). ¹³C-NMR (DMSO-d₆) δ 169.2, 168.2, 163.3, 156.7, 149.8, 138.1, 131.5, 130.6, 129.7, 127.9, 80.4, 62.6, 62.3, 62.0, 61.7, 43.2, 13.4. HRMS (ESI): m/z calcd for C₁₈H₁₈Cl₂F₃N₅O₃ [M + Na]⁺: 502.0636, found 502.0635.

N-((4-(Benzylamino)-6-(2,2,2-trifluoroethoxy)pyrimidin-2-yl)carbamoyl)-2,6-dichlorobenzamide (28). White solid, mp 76–78 °C, yield = 80%. ¹H-NMR (DMSO-d₆) δ 12.46 (d, J = 369.0 Hz, 1H, NH), 10.27 (s, 1H, NH), 8.25 (s, 1H, Ar-NH), 7.82–7.40 (m, 3H, Ph), 7.42–7.14 (m, 5H, Ph), 5.70 (s, 1H, ArH), 4.93 (q, J = 9.0 Hz, 2H, OCH₂CF₃), 4.39 (s, 2H, N–CH₂Ph). ¹³C-NMR (DMSO-d₆) δ 164.0, 155.9, 151.0, 148.6, 138.7, 136.7, 131.1, 130.8, 129.9, 128.3, 128.0, 127.9, 127.0, 126.1, 124.8, 122.6, 120.4, 81.6, 61.6, 61.3, 61.0, 60.7, 44.2, 30.6, 25.7. HRMS (ESI): m/z calcd for C₂₁H₁₆Cl₂F₃N₅O₃ [M + Na]⁺: 536.0480, found 536.0485.

N-((4-(Benzyl(ethyl)amino)-6-(2,2,2-trifluoroethoxy)pyrimidin-2-yl)carbamoyl)-2,6-dichlorobenzamide (29). White solid, mp 61–62 °C, yield = 75%. ¹H-NMR (DMSO-d₆) δ 12.72 (s, 1H, NH), 10.28 (s, 1H, NH), 7.71–7.08 (m, 8H, Ph), 5.85 (s, 1H, ArH), 4.95 (d, J = 9.0 Hz, 2H, OCH₂CF₃), 4.74 (s, 2H, N–CH₂Ph), 3.41 (d, J = 52.6 Hz, 2H, CH₂CH₃), 1.08 (s, 3H, CH₂CH₃). ¹³C-NMR (DMSO-d₆) δ 169.3, 167.5, 166.0, 165.2, 164.7, 156.6, 156.3, 133.7, 131.1, 129.8, 129.5, 129.0, 128.9, 128.1, 125.8, 123.6, 81.1, 62.5, 62.2, 61.9, 60.7, 30.9, 15.0. HRMS (ESI): m/z calcd for C₂₃H₂₀Cl₂F₃N₅O₃ [M + H]⁺: 542.0974, found 542.0971.

N-((5-(Sec-butyl)-4-chloro-6-(2,2,2-trifluoroethoxy)pyrimidin-2-yl)carbamoyl)-2,6-dichlorobenzamide (30). White solid, mp 37–38 °C, yield = 73%. ¹H-NMR (DMSO-d₆) δ 11.64 (s, 1H, NH), 10.81 (s, 1H, NH), 7.76–7.39 (m, 3H, Ph), 5.16 (q, J = 8.8 Hz, 2H, OCH₂CF₃), 3.21 (dt, J = 9.2, 6.8 Hz, 1H, CH), 1.90–1.74 (m, 1H, CHCH₂CH₃), 1.68 (dt, J = 13.8, 6.7 Hz, 1H, CHCH₂CH₃), 1.29 (d, J = 7.1 Hz, 3H, CHCH₃), 0.83 (t, J = 7.4 Hz, 3H, CHCH₂CH₃). ¹³C-NMR (DMSO-d₆) δ 167.7, 166.7, 160.4, 154.0, 148.7, 131.2, 129.1, 125.6, 123.4, 118.3, 63.9, 63.6, 63.3, 63.0, 31.6, 27.4, 18.6, 13.2. HRMS (ESI): m/z calcd for C₁₈H₁₆Cl₃F₃N₄O₃ [M + Na]⁺: 521.0138, found 521.0157.