General procedure for the synthesis of the target compounds 12a-12w and 15
To a solution of cinnamic acid 10a-10w or 13 (0.84 mmol) in methylene chloride (15 mL), oxalyl chloride (1 mmol) was added. The reaction mixture was stirred for 2-3 h at room temperature, and then evaporated to dryness in vacuo. The cinnamoyl chloride or 14 yielded was dissolved in methylene chloride (5 mL) and used in the subsequent reaction. To a solution of 6-methyl-N1-(4-pyridin-3-yl- pyrimidin-2-yl)benzene-1,3-diamine (8, 0.21 g, 0.76 mmol) and triethylamine (0.25g, 2.48 mmol) in methylene chloride (15 mL) cooled at 0 °C, the above methylene chloride solution of the cinnamoyl chloride or 14 was added dropwise and the reaction mixture was then stirred for 2-8 h at room temperature. The precipitate was collected by filtration, washed with methylene chloride and water, and air-dried to afford the corresponding cinnamamide derivatives.
(E)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]-3-phenylacrylamide (12a): yield: 74.5%; mp:181-182 °C. 1H-NMR δ: 10.12 (s, 1H, NHCO), 9.27 (d, 1H, J = 1.8, Py-2-H), 8.92 (s, 1H, NH), 8.69 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H ), 8.51 (d, 1H, J = 5.2, pyrimidinyl-6-H), 8.46 (dt, 1H, J1 = 8.0, J2 = 1.8, Py-4-H), 7.99 (d, 1H, J = 1.6), 7.61 (d, 2H, J = 7.1), 7.57 (d, 1H, J = 15.8, COCH=CH), 7.54 (dd, 1H, J1 = 7.9, J2 = 4.8, Py-5-H), 7.46-7.39 (m, 5H), 7.19 (d, 1H, J = 8.3), 6.84 (d, 1H, J = 15.8, COCH=CH), 2.21 (s, 3H, CH3); HRMS m/z calcd. for C25H21N5ONa [M+Na]+ 430.16438, found: 430.21130.
(E)-3-(2-fluoropheny)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acrylamide (12b): yield: 76.8%; mp: 243-245 °C. 1H-NMR δ: 10.26 (s, 1H, NHCO), 9.28 (d, 1H, J = 1.6, Py-2-H), 8.95 (s, 1H, NH), 8.69 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H), 8.52 (d, 1H, J = 5.1, pyrimidinyl-6-H), 8.48 (dt, 1H, J1 = 8.0, J2 = 1.9, Py-4-H), 8.04 (d, 1H, J = 1.9), 7.84 (d, 1H, J = 15.6, COCH=CH ), 7.76-7.71 (m, 2H), 7.54 (dd, 1H, J1 = 7.9, J2 = 4.8, Py-5-H), 7.50 (t, 1H, J = 8.4), 7.44 (d, 2H, J = 5.2), 7.37-7.34 (m, 1H), 7.21 (d, 1H, J = 8.3), 6.87 (d, 1H, J = 15.6, COCH=CH), 2.21 (s, 3H, CH3); HRMS m/z calcd. for C25H21FN5O [M+H] + 426.17301, found: 426.20733.
(E)-3-(2-chlorophenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acrylamide (12c): yield: 77.8%; mp: 270-272 °C. 1H-NMR δ: 10.24 (s, 1H, NHCO), 9.27 (d, 1H, J = 1.8, Py-2-H), 8.92 (s, 1H, NH), 8.69 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H), 8.52 (d, 1H, J = 5.2, pyrimidinyl-6-H), 8.48 (dt, 1H, J1 = 8.0, J2 = 1.9, Py-4-H), 8.01 (d, 1H, J = 1.6), 7.87 (d, 1H, J = 15.5, COCH=CH), 7.78-7.76 (m, 1H), 7.56-7.51 (m, 2H), 7.45-7.42 (m, 4H), 7.20 (d, 1H, J = 8.3), 6.90 (d, 1H, J = 15.5, COCH=CH), 2.21 (s, 3H, CH3); HRMS m/z calcd. for C25H21ClN5O [M+H] + 442.14346, found: 442.14943.
(E)-3-(2-bromophenyl)-N-[4-methyl-3-(4-(pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acrylamide (12d): yield: 80.8%; mp: 268-269 °C. 1H-NMR δ: 10.26 (s, 1H, NHCO), 9.28 (d, 1H, J = 1.7, Py-2-H), 8.95 (s, 1H, NH), 8.69 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H), 8.52 (d, 1H, J = 5.1, pyrimidinyl-6-H), 8.49 (dd, 1H, J1 = 8.0, J2 = 1.8, Py-4-H), 8.04 (d, 1H, J = 1.9), 7.84 (d, 1H, J = 15.6, COCH=CH ), 7.76-7.71 (m, 2H), 7.54 (dd, 1H, J1 = 7.9, J2 = 4.8, Py-5-H), 7.50 (t, 1H, J = 5.2), 7.44 (d, 2H, J = 5.2), 7.37-7.34 (m, 1H), 7.21 (d, 1H, J = 8.3), 6.87 (d, 1H, J = 15.6, COCH=CH), 2.21 (s, 3H, CH3); HRMS m/z calcd. for C25H21BrN5O [M+H] + 486.09295, found: 486.09298.
(E)-N-[4-methyl-3-(4-(pyridin-3-yl-pyrimidin-2-ylamino)phenyl]-3-(2-nitrophenyl)acrylamide (12e): yield: 78.8%; mp: 270-272 °C. 1H-NMR δ: 10.26 (s, 1H, NHCO), 9.27 (d, 1H, J = 1.8, Py-2-H), 8.92 (s, 1H, NH), 8.68 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H), 8.52 (d, 1H, J = 5.1, pyrimidinyl-6-H), 8.49 (dt, 1H, J1 = 8.0, J2 = 1.8, Py-4-H), 8.08 (d, 1H, J = 7.9), 8.01 (d, 1H, J = 1.8), 7.84 (d, 1H, J = 15.8, COCH=CH), 7.82-7.80 (m, 2H), 7.68-7.65 (m, 1H), 7.53 (dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.44-7.40 (m, 2H), 7.21 (d, 1H, J = 8.4), 6.83 (d, 1H, J = 15.5, COCH=CH), 2.22 (s, 3H, CH3); HRMS m/z calcd. for C25H20N6O3Na [M+Na]+ 475.14946, found: 475.16374.
(E)-3-(2-methoxyphenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acrylamide (12f): yield: 66.3%; mp: 246-247 °C. 1H-NMR δ: 10.08 ( s, 1H, NHCO), 9.26 (d, 1H, J = 1.7, Py-2-H), 8.92 (s, 1H, NH), 8.69 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H ), 8.51 (d, 1H, J = 5.2, pyrimidinyl-6-H), 8.46 (dt, 1H, J1 = 8.0, J2 = 1.9, Py-4-H), 7.99 (d, 1H, J = 1.8), 7.79 (d, 1H, J = 15.8, COCH=CH), 7.56 (dd, 1H, J1 = 7.8, J2 = 1.5), 7.53(dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.43-7.37 (m, 3H), 7.18 (d, 1H, J = 8.3), 7.10 (d, 1H, J = 8.2), 7.01 (t, 1H, J = 7.5), 6.87 (d, 1H, J = 15.8, COCH=CH), 3.89 (s, 3H, OCH3) 2.21(s, 3H, CH3); HRMS m/z calcd. for C26H23N5O2Na [M+Na]+ 460.17494, found: 460.16676.
(E)-3-(2-ethoxyphenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acrylamide (12g): yield: 66.6%; mp: 255-257 °C. 1H-NMR δ: 10.09 ( s, 1H, NHCO), 9.26 (d, 1H, J = 1.8, Py-2-H), 8.92 ( s,1H, NH), 8.69 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H ), 8.51 (d, 1H, J = 5.1, pyrimidinyl-6-H), 8.48 (dt, 1H, J1 = 8.0, J2 = 1.9, Py-4-H), 8.01 (d, 1H, J = 1.6), 7.84 (d, 1H, J = 15.8, COCH=CH), 7.57 (dd, 1H, J1 = 7.8, J2 = 1.3), 7..53 (dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.43-7.40 (m, 2H), 7.38-7.35 (m, 1H), 7.18 (d, 1H, J = 8.3), 7.08 (d, 1H, J = 8.3), 7.01 (t, 1H, J = 7.5), 6.85 (d, 1H, J = 15.8, COCH=CH), 4.15 (q, 2H, J = 7.0, OCH2CH3).), 2.22 (s, 3H, CH3), 1.41(t, 3H, J = 7.0, OCH2CH3); HRMS m/z calcd. for C27H26N5O2 [M+H]+ 452.20865, found: 452.24296.
(E)-3-(4-fluorophenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acrylamide (12h): yield: 70.6%; mp: 194-198 °C. 1H-NMR δ: 10.28 (s, 1H, NHCO), 9.26 (d, 1H, J = 1.8, Py-2-H), 8.92 (s, 1H, NH), 8.68 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H ), 8.51 (d, 1H, J = 5.1, pyrimidinyl-6-H), 8.47 (dt, 1H, J1 = 8.0, J2 = 1.9, Py-4-H), 7.97(d, 1H, J = 1.9), 7.68 (dd, 2H, J1 = 8.5, J2 = 5.5), 7.56 (d, 1H, J = 15.8, COCH=CH), 7.53 (dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.43 (d, 1H, J = 5.3), 7.40 (d, 1H, J = 2.0), 7.28 (t, 2H, J1 = 8.5), 7.19 (d, 1H, J = 8.4), 6.78 (d, 1H, J = 15.8, COCH=CH), 2.22 (s, 3H, CH3); HRMS m/z calcd. for C25H20FN5ONa [M+Na]+ 448.15496, found: 448.13271.
(E)-3-(4-chlorophenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acrylamide (12i): yield: 65.8%; mp:268-269 °C. 1H-NMR δ: 10.14 (s, 1H, NHCO), 9.26 (d, 1H, J = 1.8, Py-2-H), 8.92 (s, 1H, NH), 8.69 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H), 8.51 (d, 1H, J = 5.2, pyrimidinyl-6-H), 8.46 (dt, 1H, J1 = 8.0, J2 = 2.0, Py-4-H), 7.98 (d, 1H, J = 1.6), 7.64 (d, 2H, J = 8.6), 7.56 (d, 1H, J = 15.6, COCH=CH), 7.53 (dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.50 (t, 2H, J1 = 8.5), 7.43 (d, 1H, J = 5.2), 7.41 (d, 1H, J = 1.9), 7.19 (d, 1H, J = 8.3), 6.84 (d, 1H, J = 15.6, COCH=CH ), 2.21 (s, 3H, CH3); HRMS m/z calcd. for C25H21ClN5O [M+H] + 442.14346, found: 442.14943.
(E)-3-(4-bromophenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acrylamide (12j): yield: 49.6%; mp:124-125 °C. 1H-NMR δ: 10.14 (s, 1H, NHCO), 9.26 (d, 1H, J = 1.8, Py-2-H), 8.92 (s, 1H, NH), 8.69 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H), 8.52 (d, 1H, J = 5.1, pyrimidinyl-6-H), 8.46 (dt, 1H, J1 = 8.0, J2 = 1.9, Py-4-H), 7.98 (d, 1H, J = 1.5), 7.64 (d, 2H, J = 8.5), 7.59 (d, 1H, J = 15.6, COCH=CH), 7.53 (dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.50 (t, 2H, J1 = 8.5), 7.43 (d, 1H, J = 5.2), 7.41 (d, 1H, J = 1.9), 7.19 (d, 1H, J = 8.3), 6.86 (d, 1H, J = 15.7, COCH=CH ), 2.21 (s, 3H, CH3); HRMS m/z calcd. for C25H20BrN5ONa [M+Na]+ 508.07489, found: 508.05714.
(E)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]-3-(4-nitrophenyl)acrylamide (12k): yield: 70.0%; mp: 252-254 °C. 1H-NMR δ: 10.28 (s, 1H, NHCO), 9.27 (d, 1H, J = 1.8, Py-2-H), 8.94 (s, 1H, NH), 8.69 (dd, 1H, J1 = 4.8, J2 = 1.7, Py-6-H), 8.52 (d, 1H, J = 5.2, pyrimidinyl-6-H), 8.47 (dt, 1H, J1 = 8.0 Hz, J2 = 1.9, Py-4-H), 8.29-8.27 (m, 2H), 8.00 (d, 1H, J = 1.9) 7.89 (d, 2H, J = 8.9), 7.67 (d, 1H, J = 15.8, COCH=CH), 7.53 (dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.44-7.42 (m, 2H), 7.21 (d,1H, J = 8.4), 7.02 (d, 1H, J = 15.8, COCH=CH), 2.22 (s, 3H, CH3); HRMS m/z calcd. for C25H20N6O3Na [M+Na]+ 475.14946, found: 475.13600.
(E)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]-3-p-tolylacrylamide (12l): yield: 68.8%; mp: 205-208 °C. 1H-NMR δ: 10.07 (s, 1H, NHCO), 9.26 (d, 1H, J = 1.8, Py-2-H), 8.92 (s, 1H, NH), 8.68 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H), 8.51 (d, 1H, J = 5.1, pyrimidinyl-6-H), 8.47 (dt, 1H, J1 = 8.1, J2 = 1.9, Py-4-H), 7.97 (d, 1H, J = 1.9), 7.53 (dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.52 (d, 1H, J = 15.6, COCH=CH), 7.50 (d, 2H, J = 8.0), 7.42 (d, 1H, J = 5.2), 7.40 (d, 1H, J = 2.0), 7.25 (d, 2H, J = 8.0), 7.18 (d, 1H, J = 8.4), 6.78 (d, 1H, J = 15.7, COCH=CH), 2.33 (s, 3H, CH3), 2.22 (s, 3H, CH3); HRMS m/z calcd. for C25H24N5O [M+H]+ 442.19809, found: 422.19907
(E)-3-(4-methoxyphenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acrylamide (12m): yield: 63.3%; mp: 115-117 °C. 1H-NMR δ: 10.03 (s, 1H, NHCO), 9.27 (d, 1H, J = 1.8, Py-2-H), 8.92 (s,1 H, NH), 8.69 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H ), 8.51 (d, 1H, J = 5.1, pyrimidinyl-6-H), 8.46 (dt, 1H, J1 = 8.0, J2 = 1.9, 1H, Py-4-H), 7.97 (d, 1H, J = 1.7), 7.56 (d, 2H, J = 8.8), 7.53 (dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.52 (d, 1H, J = 15.6, COCH=CH), 7.42 (d, 1H, J = 5.2), 7.40 (d, 1H, J = 2.0), 7.18 (d, 1H, J = 8.4), 7.01 (d, 2H, J = 8.8), 6.69 (d, 1H, J = 15.7, COCH=CH), 3.80 (s, 3H, OCH3), 2.21 (s, 3H, CH3); HRMS m/z calcd. for C26H24N5O2 [M+H]+ 438.19300, found: 438.17750.
(E)-3-(4-benzyloxyphenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acrylamide (12n): yield: 51.4%; mp: 221-222 °C. 1H-NMR δ: 10.02 (s, 1H, NHCO), 9.26 (d, 1H, J = 1.8, Py-2-H), 8.91 (s, 1H, NH), 8.69 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H ), 8.49 (d, 1H, J = 5.1, pyrimidinyl-6-H), 8.45 (dt, 1H, J1 = 8.1, J2 = 1.9, Py-4-H), 7.97 (d, 1H, J = 1.7), 7.56 (d, 2H, J = 8.7), 7.53 (dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.51 (d, 1H, J = 15.7, COCH=CH), 7.45 (d, 2H, J = 7.3), 7.43-7.39 (m, 4H), 7.35-7.32 (m, 1H), 7.18 (d, 1H, J = 8.4), 7.08 (d, 2H, J = 8.7), 6.70 (d, 1H, J = 15.6, COCH=CH), 5.20 (s, 2H, OCH2Ph), 2.20 (s, 3H, CH3); HRMS m/z calcd. for C32H28N5O2 [M+H]+ 514.22430, found: 514.23057.
(E)-3-(2,3-dimethoxyphenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acrylamide (12o): yield: 33.9%; mp: 146-147 °C. 1H-NMR δ: 10.13 (s, 1H, NHCO), 9.27 (d, 1H, J = 1.8, Py-2-H ), 8.91(s, 1H, NH), 8.69 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H ), 8.52 (d, 1H, J = 5.1, pyrimidinyl-6-H), 8.46 (dt, 1H, J1 = 8.0, J2 = 1.9, Py-4-H), 8.00 (d, 1H, J = 1.5), 7.76 (d, 1H, J = 15.8, COCH=CH), 7.53 (dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.43 (d, 1H, J = 5.1), 7.41 (d, 1H, J = 1.9), 7.20-7.18 (m, 2H), 7.14 (t, 1H, J = 8.0), 7.10 (dd, 1H, J1 = 8.1, J2 = 1.7), 6.87 (d, 1H, J = 15.8, COCH=CH ), 3.84 (s, 3H, OCH3), 3.78 (s, 3H, OCH3), 2.21 (s, 3H, CH3); HRMS m/z calcd. for C27H25N5O3Na [M+Na]+ 490.18551, found: 490.19200.
(E)-3-(2,4-dimethoxyphenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acrylamide (12p): yield: 65.1%; mp:154-156 °C. 1H-NMR δ: 9.98 (s, 1H, NHCO), 9.26 (d, 1H, J = 1.8, Py-2-H), 8.91(s, 1H, NH), 8.69 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H), 8.51 (d, 1H, J = 5.1, pyrimidinyl-6-H), 8.46 (dt, 1H, J1 = 8.1, J2 = 1.9, Py-4-H), 7.97 (d, 1H, J = 1.9), 7.70 (d, 1H, J = 15.7, COCH=CH), 7.53 (dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.50 (d, 1H, J = 8.5), 7.42 (d, 1H, J = 5.1), 7.40 (d, 1H, J = 1.9), 7.17 (d, 1H, J = 8.4), 6.74 (d, 1H, J = 15.7, COCH=CH), 6.61-6.60 (m, 2H), 3.88 (s, 3H, OCH3), 3.82 (s, 3H, OCH3), 2.21 (s, 3H, CH3); HRMS m/z calcd. for C27H25N5O3Na [M+Na]+ 490.18551, found: 490.19263.
(E)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]-3-(2,3,4–trimethoxyphenyl) acrylamide (12q): yield: 69.0%; mp:226-227 °C. 1H-NMR δ: 10.05 (s, 1H, NHC=O), 9.26 (d, 1H, J = 1.8, Py-2-H), 8.91(s, 1H, NH), 8.69 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H), 8.51(d, 1H, J = 5.1, pyrimidinyl-6-H), 8.48 (dt, 1H, J1 = 8.1, J2 = 1.9, Py-4-H), 7.99 (d, 1H, J = 1.9), 7.65 (d, 1H, J = 15.8, COCH=CH), 7.53 (dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.43 (d, 1H, J = 5.1), 7.40 (d, 1H, J = 1.9), 7.33 (d, J = 8.8), 7.18 (d, 1H, J = 8.4), 6.91( d, 1H, J = 8.8), 6.79 (d, 1H, J = 15.8, COCH=CH), 3.84 (s, 3H, OCH3), 3.83 (s, 3H, OCH3), 3.78 (s, 3H, OCH3), 2.21 (s, 3H, CH3); HRMS m/z calcd. for C28H27N5O4Na [M+Na]+ 520.19607, Found: 520.19694.
(E)-3-(3,4-dimethoxyphenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acrylamide (12r): yield: 67.8%; mp: 234-235 °C. 1H-NMR δ: 10.03 (s, 1H, NHCO), 9.27 (d, 1H, J = 1.8, Py-2-H), 8.92 (s,1H, NH), 8.69 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H ), 8.50 (d, 1H, J = 5.1, pyrimidinyl-6-H), 8.46 (dt, 1H, J1 = 8.1, J2 = 1.9, Py-4-H), 7.98 (d, 1H, J = 1.9), 7.53 (dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.50 (d, 1H, J = 15.8, COCH=CH), 7.42-7.40 (m, 2H), 7.21 (d, 1H, J = 1.8), 7.18 (dd, 2H, J1 = 8.6, J2 = 3.1), 7.01 (d, 1H, J = 8.4), 6.71(d, 1H, J = 15.8, COCH=CH), 3.82 (s, 3H, OCH3), 3.80 (s, 3H, OCH3), 2.21 (s, 3H, CH3); HRMS m/z calcd. for C27H26N5O3 [M+H]+ 468.20357, found: 468.20356.
(E)-3-(4-ethoxy-3-methoxyphenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino]phenyl]acryla-mide (12s): yield: 68.8%; mp: 256-258 °C. 1H-NMR δ: 10.03 (s, 1H, NHCO), 9.26 (d, 1H, J = 1.8, Py-2-H), 8.92 (s, 1H, NH), 8.68 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H), 8.51(d, 1H, J = 5.2, pyrimidinyl-6-H), 8.47 (dt, 1H, J1 = 8.1, J2 = 1.9 Py-4-H), 7.97 (d, 1H, J = 1.9), 7.53 (dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.50 (d, 1H, J = 15.6,COCH=CH), 7.42 (d,1H, J = 5.1), 7.40 (d, 1H, J = 2.0), 7.20 (d, 1H, J = 1.9), 7.18 (d, 1H, J = 8.4), 7.15 (dd, 1H, J1 = 8.4, J2 = 1.9), 6.99 (d, 1H, J = 8.4), 6.70 (d, 1H, J = 15.7, COCH=CH ), 4.05 (q, 2H, J = 7.0, OCH2CH3), 3.81 (s, 3H, OCH3), 2.22 (s, 3H, CH3), 1.34 (t, 3H, J = 7.0, OCH2CH3); HRMS m/z calcd. for C28H28N5O3 [M+H]+ 482.21921, found: 482.22009.
(E)-3-(3-ethoxy-4-methoxyphenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acryla-mide (12t): yield: 68.5%; mp: 263-264 °C. 1H-NMR δ: 10.01 (s, 1H, NHC=O), 9.26 (d, 1H, J = 1.8, Py-2-H), 8.92 (s, 1H, NH), 8.68 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H), 8.51 (d, 1H, J = 5.2, pyrimidinyl -6-H), 8.47 (dt, 1H, J1 = 8.1, J2 = 1.9, Py-4-H), 7.97 (d, 1H, J = 1.9), 7.53 (dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.50 (d, 1H, J = 15.6, COCH=CH)), 7.42 (d,1H, J = 5.1), 7.40 (d, 1H, J = 2.1), 7.19-7.16 (m, 3H), 7.00 (d,1H, J = 8.4), 6.70 (d, 1H, J = 15.7, COCH=CH), 4.06(q, 2H, J = 6.9, OCH2CH3) 3.80 (s, 3H, OCH3), 2.21 (s, 3H, CH3), 1.35 (t, 3H, J = 6.9, OCH2CH3); HRMS m/z calcd. for C28H28N5O3 [M+H]+ 482.21921, Found: 482.22036.
(E)-3-(4-benzyloxy-3-methoxyphenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl] acrylamide (12u): yield: 36.4%; mp: 178-179 °C. 1H-NMR δ: 10.08 ( s, 1H, NHCO), 9.27 (d, 1H J = 1.8, Py-2-H), 8.98 (s, 1H, NH), 8.69 (dd, 1H, J1= 4.8, J2 = 1.6, Py-6-H ), 8.51 (d, 1H, J = 5.1, pyrimidinyl-6-H), 8.46 (dt, 1H, J1 = 8.1, J2 = 1.9, Py-4-H), 7.97 (d, 1H, J = 1.7), 7.53 (dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.51 (1H, J = 15.7, COCH=CH), 7.49-7.47 (m, 2H), 7.44-7.40 (m, 4H), 7.36-7.33 (m, 1H), 7.33 (d, 1H, J = 1.6), 7.22 (dd, 1H, J1 = 8.4, J2 = 1.8), 7.18 (d, 1H, J = 8.4), 7.05 (d, 1H, J = 8.7), 6.70 (d, 1H, J = 15.6, COCH=CH), 5.20 (s, 2H, OCH2Ph), 3.83 (s, 3H, OCH3), 2.20 (s, 3H, CH3);HRMS m/z calcd. for C33H30N5O3 [M+H]+ 544.23486, found: 544.23565.
(E)-3-(3-benzyloxy-4-methoxyphenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl] acrylamide (12v) yield: 42.7%; mp: 232-234 °C. 1H-NMR δ: 10.04 ( s, 1H, NHCO), 9.27(d, 1H, J = 1.8, Py-2-H), 8.92( s,1 H, NH), 8.69 (dd, 1H, J1 = 4.8, J2 = 1.6, Py-6-H ), 8.51 (d, 1H, J = 5.1, pyrimidinyl-6-H), 8.46 (dt, 1H, J1 = 8.1, J2 = 1.9, Py-4-H), 7.97 (d, 1H, J = 1.7), 7.53 (dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.50 (d, 1H, J = 15.8, COCH=CH), 7.46-7.44 (m, 2H), 7.42-7.38 (m, 4H), 7.35-7.33 (m, 1H), 7.23 (d, 1H, J = 1.9), 7.18 (d, 1H, J = 8.4), 7.15 (dd, 1H, J1 = 8.4, J2 = 1.8), 7.09 (d, 1H, J = 8.4), 6.70 (d, 1H, J = 15.6, COCH=CH), 5.13 (s, 2H, OCH2Ph), 3.83 (s, 3H, OCH3), 2.20 (s, 3H, CH3); HRMS m/z calcd. for C33H30N5O3 [M+H]+ 544.23486, found: 544.23565.
(E)-3-benzo[1,3]dioxol-5-yl-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acrylamide (12w): yield: 46.8%; mp: 244-246 °C. 1H-NMR δ: 10.02 (s, 1H, NHCO), 9.26 (d, 1H, J = 1.2, Py-2-H), 8.91 (s, 1H, NH), 8.69 (dd, 1H, J1 = 4.5, J2 = 1.1, Py-6-H), 8.51 (d, 1H, J =5.1, pyrimidinyl-6-H), 8.46 (dt, 1H, J1 = 8.1, J2 = 1.9, Py-4-H), 7.97 (d, 1H, J = 1.3), 7.53 (dd, 1H, J1 = 8.0, J2 = 4.8, Py-5-H), 7.49 (d, 1H, J=15.6, COCH=CH), 7.42 (d, 1H, J = 5.1), 7.40 (d, 1H, J = 1.6), 7.18 (d, 2H, J = 7.2), 7.13 (dd, 1H, J1 = 8.1, J2 = 1.4), 6.97 (d, 1H, J = 8.0), 6.67 (d, 1H, J = 15.6, COCH=CH), 6.08 (s, 2H, OCH2O), 2.21 (s, 3H, CH3); HRMS m/z calcd. for C26H21N5O3Na [M+Na]+ 474.15421, found: 474.14769.
N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]-3-p-tolylpropionamide (15): yield: 76.6%; mp: 168-169°C. 1H-NMR δ: 9.81(s, 1H, NHCO), 9.26 (d, 1H, J = 1.8, Py-2-H), 8.90 (s, 1H, NH), 8.69 (dd, 1H, J1 = 4.7, J2 = 1.6, Py-6-H ), 8.50 (d, 1H, J = 5.1, pyrimidinyl-6-H), 8.46 (dt, 1H, J1 = 8.0, J2 = 1.8, Py-4-H), 7.88 (d, 1H, J = 1.6), 7.51 (dd, 1H, J1 = 8.0 Hz, J2 = 4.8, Py-4-H), 7.41 (d, 1H, J = 5.1), 7.28 (dd, 1H, J1 = 8.0, J2 = 1.8), 7.14-7.12 (m, 3H), 7.07 (d, 2H, J = 8.0), 2.86 (t, 2H, J = 7.45, COCH2CH2), 2.58 (t, 2H, J = 7.45, COCH2CH2), 2.24 (s, 3H, CH3), 2.19 (s, 3H, CH3); HRMS m/z calcd. for C26H26N5O [M+H]+ 424.21374, found: 424.24776.