3.11. Analytics of the Synthesized Compounds
2-chloro-4-phenylpyrimidine (3): white solid, Mp 86–87 °C (lit. 84–86 °C [
41]);
1H NMR (400 MHz, CDCl
3): δ (ppm) = 7.48–7.54 (m, 3H), 7.64 (d,
J = 5.3 Hz, 1H), 8.07–8.10 (m, 2H), 8.63 (d,
J = 5.3 Hz, 1H);
13C NMR (100 MHz, CDCl
3): δ (ppm) = 115.27, 127.55, 129.25, 132.04, 135.17, 159.95, 161.99, 167.30; HRMS (ESI+)
m/z calc. for C
10H
8N
2Cl [M + H]
+ 191.0371, found 191.0369; HPLC
tR = 6.41 min; Rf = 0.43 (EtOAc/n-Hex, 1:2,
v/v).
4-chloro-2-phenylpyrimidine (4): white solid, Mp 72–73 °C (lit. 73–74 °C [
42]);
1H NMR (400 MHz, CDCl
3): δ (ppm) = 7.23 (d,
J = 5.2 Hz, 1H), 7.48–7.52 (m, 3H), 8.43–8.46 (m, 2H), 8.67 (d,
J = 5.2 Hz, 1H);
13C NMR (100 MHz, CDCl
3): δ (ppm) = 119.45, 128.66, 128.81, 131.68, 136.23, 158.39, 161.70, 165.71; HRMS (ESI+)
m/z calc. for C
10H
8N
2Cl [M + H]
+ 191.0371, found 191.0371; HPLC
tR = 7.09 min; Rf = 0.55 (EtOAc/n-Hex, 1:2,
v/v).
2-chloro-4-(2-methoxyphenyl)pyrimidine (26): Yield: 76%; white solid; Mp 53–54 °C;
1H NMR (400 MHz, CDCl
3): δ (ppm) = 3.92 (s, 3H), 7.00–7.04 (m, 1H), 7.11 (td,
J1 = 1.1 Hz, J2 = 7.6 Hz, 1H), 7.48 (ddd, J1 = 1.8 Hz, J2 = 7.4 Hz, J3 = 8.4 Hz, 1H), 7.97 (d, J = 5.3 Hz, 1H), 8.09 (dd,
J1 = 1.8 Hz,
J2 = 7.8 Hz, 1H), 8.57 (d,
J = 5.3 Hz, 1H) as reported [
43];
13C NMR (100 MHz, CDCl
3): δ (ppm) = 55.76, 111.65, 120.21, 121.43, 124.53, 131.47, 13.86, 158.32, 159.05, 161.31, 165.82; HRMS (ESI+)
m/z calc. for C
10H
10N
2OCl [M + H]
+ 221.0476, found 221.0476; HPLC
tR = 6.41 min; Rf = 0.36 (EtOAc/n-Hex, 1:4,
v/v).
2-chloro-4-(3-methoxyphenyl)pyrimidine (27): Yield: 72%; white solid; Mp 68–70 °C (lit. 83–86 °C [
44]);
1H NMR (400 MHz, CDCl
3): δ (ppm) = 3.90 (s, 3H), 7.09 (ddd,
J1 = 0.9 Hz,
J2 = 2.6 Hz,
J3 = 8.2 Hz, 1H), 7.42 (t,
J = 8.0 Hz, 1H), 7.63 (d,
J = 5.3 Hz, 1H), 7.61–7.67 (m, 2H), 8.64 (d,
J = 5.3 Hz, 1H);
13C NMR (100 MHz, CDCl
3): δ (ppm) = 55.67, 112.61, 115.48, 118.06, 119.92, 130.29, 136.64, 159.97, 160.41, 161.99, 167.17; HRMS (ESI+)
m/z calc. for C
10H
10N
2OCl [M + H]
+ 221.0476, found 221.0476; HPLC
tR = 6.34 min; Rf = 0.24 (EtOAc/n-Hex, 1:4,
v/v).
2-chloro-4-(4-methoxyphenyl)pyrimidine (28): Yield: 77%; white solid; Mp 106–108 °C (lit. 137–140 °C [
44]);
1H NMR (400 MHz, CDCl
3): δ (ppm) = 3.89 (s, 3H), 6.99–7.03 (m, 2H), 7.57 (d,
J = 5.3 Hz, 1H), 8.06–8.10 (m, 2H), 8.56 (d,
J = 5.3 Hz, 1H);
13C NMR (100 MHz, CDCl
3): δ (ppm) = 55.65, 114.32, 114.63, 127.57, 129.30, 159.58, 161.90, 162.96, 166.79; HRMS (ESI+)
m/z calc. for C
11H
10ON
2Cl [M + H]
+ 221.0476, found 221.0476; HPLC
tR = 6.30 min; Rf = 0.18 (EtOAc/n-Hex, 1:4,
v/v).
2-chloro-4-(m-tolyl)pyrimidine (29): Yield: 75%; white solid; Mp 74–75 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) = 2.45 (s, 3H), 7.34–7.38 (m, 1H), 7.40 (t, J = 7.5 Hz, 1H), 7.64 (d, J = 5.3 Hz, 1H), 7.84–7.87 (m, 1H), 7.92–7.94 (m, 1H), 8.62 (d, J = 5.3 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) = 21.59, 115.38, 124.72, 128.18, 129.16, 132.87, 135.18, 139.16, 159.88, 161.98, 167.56; HRMS (ESI+) m/z calc. for C11H10N2Cl [M + H]+ 205.0527, found 205.0529; HPLC tR = 6.87 min; Rf = 0.35 (EtOAc/n-Hex, 1:3, v/v).
2-chloro-4-(3-nitrophenyl)pyrimidine (30): Yield: 79%; yellow solid; Mp 123–125 °C;
1H NMR (400 MHz, CDCl
3): δ (ppm) = 7.74 (t,
J = 8.0 Hz, 1H), 7.76 (d,
J = 5.2 Hz, 1H), 8.41 (ddd,
J1 = 1.1 Hz,
J2 = 2.2 Hz,
J3 = 8.2 Hz, 1H), 8.48 (ddd,
J1 = 1.1 Hz,
J2 = 1.8 Hz,
J3 = 7.8 Hz, 1H), 8.76 (d,
J = 5.2 Hz, 1H), 8.93 (t,
J = 1.9 Hz, 2H) as reported [
45];
13C NMR (100 MHz, CDCl
3): δ (ppm) = 115.46, 122.46, 126.40, 130.48, 133.26, 136.96, 149.01, 160.77, 162.37, 164.64; HRMS (ESI+)
m/z calc. for C
10H
7O
2N
3Cl [M + H]
+ 236.0221, found 236.0221; HPLC
tR = 6.33 min; Rf = 0.17 (EtOAc/n-Hex, 1:2,
v/v).
3-(2-chloropyrimidin-4-yl)benzonitrile (31): Yield: 83%; pale pink solid; Mp 180–182 °C;
1H NMR (400 MHz, CDCl
3): δ (ppm) = 7.64–7.68 (m, 1H), 7.68 (d,
J = 5.2 Hz, 1H), 7.83 (dt,
J1 = 1.4 Hz,
J2 = 7.7 Hz, 1H), 8.33 (ddd,
J1 = 1.2 Hz,
J2 = 1.9 Hz,
J3 = 8.0 Hz, 1H), 8.41 (t,
J = 1.8 Hz, 1H), 8.74 (d,
J = 5.2 Hz, 1H) as reported [
46];
13C NMR (100 MHz, CDCl
3): δ (ppm) = 113.84, 115.31, 118.10, 130.23, 131.18, 131.56, 135.00, 136.47, 160.70, 162.34, 164.79; HRMS (ESI+)
m/z calc. for C
11H
7N
3Cl [M + H]
+ 216.0323, found 216.0323; HPLC
tR = 5.97 min; Rf = 0.17 (EtOAc/n-Hex, 1:2,
v/v).
3-(2-chloropyrimidin-4-yl)benzaldehyde (32): Yield: 70%; white solid; Mp 120–122 °C;
1H NMR (400 MHz, CDCl
3): δ (ppm) = 7.70 (t,
J = 7.7 Hz, 1H), 7.74 (d,
J = 5.3 Hz, 1H), 8.05 (dt,
J1 = 1.4 Hz,
J2 = 7.6 Hz, 1H), 8.38 (dt,
J1 = 1.5 Hz,
J2= 7.7 Hz, 1H), 8.58 (t,
J = 1.8 Hz, 1H), 8.71 (d,
J = 5.1 Hz, 1H), 10.12 (s, 1H);
13C NMR (100 MHz, CDCl
3): δ (ppm) = 115.40, 128.63, 130.11, 132.71, 133.13, 136.22, 137.19, 160.45, 162.17, 165.78, 191.58; HRMS (ESI+)
m/z calc. for C
11H
8ON
2Cl [M + H]
+ 219.0320, found 219.0322 as reported [
47]; HPLC
tR = 5.61 min; Rf = 0.32 (EtOAc/n-Hex, 1:1,
v/v).
Methyl 3-(2-chloropyrimidin-4-yl)benzoate (33): Yield: 62%; white solid; Mp 108–110 °C;
1H NMR (400 MHz, CDCl
3): δ (ppm) = 3.97 (s, 3H), 7.61 (t,
J = 7.8 Hz, 1H), 7.72 (d,
J = 5.3 Hz, 1H), 8.20 (dt,
J1 = 1.4 Hz,
J2 = 7.8 Hz, 1H), 8.34 (ddd,
J1 = 1.2 Hz,
J2 = 1.9 Hz,
J3 = 7.9 Hz, 1H), 8.68 (d,
J = 5.3 Hz, 1H), 8.69–8.70 (m, 1H) as reported [
48];
13C NMR (100 MHz, CDCl
3): δ (ppm) = 52.58, 115.42, 128.57, 129.52, 131.30, 131.88, 132.86, 135.61, 160.28, 162.13, 166.24, 166.43; HRMS (ESI+)
m/z calc. for C
12H
10O
2N
2Cl [M + H]
+ 249.0425, found 249.0424; HPLC
tR = 6.29 min; Rf = 0.25 (EtOAc/n-Hex, 1:2,
v/v).
3-(2-chloropyrimidin-4-yl)benzoic acid (34): Yield: 55%; white solid; Mp 196–198 °C;
1H NMR (400 MHz, DMSO-
d6): δ (ppm) = 7.49 (t,
J = 7.7 Hz, 1H), 8.12–8.16 (m, 3H), 8.72–8.74 (m, 1H), 8.76 (d,
J = 5.3 Hz, 1H), 1H from COOH is exchanged as reported [
47];
13C NMR (100 MHz, DMSO-
d6): δ (ppm) = 116.07, 128.19, 128.28, 132.80, 133.70, 140.01, 160.51, 161.08, 166.51, 169.84; HRMS (ESI–)
m/z calc. for C
11H
6O
2N
2Cl [M − H]
– 233.0123, found 233.0122; HPLC
tR = 4.96 min; Rf = 0.14 (DCM/MeOH, 9:1,
v/v).
3-(2-chloropyrimidin-4-yl)aniline (35): Yield: 55%; yellow solid; Mp 120–122 °C (lit. 137–138 °C [
49]);
1H NMR (400 MHz, CDCl
3): δ (ppm) = 3.86 (s, 2H), 6.85 (ddd,
J1 = 1.0 Hz,
J2 = 2.4 Hz,
J3 = 7.9 Hz, 1H), 7.28 (t,
J = 7.9 Hz, 1H), 7.38 (ddd,
J1 = 1.0 Hz,
J2 = 1.8 Hz,
J3 = 7.9 Hz, 1H), 7.48 (t,
J = 2.0 Hz, 1H), 7.60 (d,
J = 5.3 Hz, 1H), 8.61 (d,
J = 5.3 Hz, 1H);
13C NMR (100 MHz, CDCl
3): δ (ppm) = 113.67, 115.41, 117.61, 118.60, 130.15, 136.21, 147.37, 159.83, 161.86, 167.51; HRMS (ESI+)
m/z calc. for C
10H
9N
3Cl [M + H]
+ 206.0480, found 206.0478; HPLC
tR = 3.35 min; Rf = 0.23 (EtOAc/n-Hex, 1:1,
v/v).
2-chloro-4-(4-fluorophenyl)pyrimidine (36): Yield: 62%; white solid; Mp 101–103 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) = 7.18–7.24 (m, 2H), 7.61 (d, J = 5.3 Hz, 1H), 8.10–8.15 (m, 2H), 8.64 (d, J = 5.3 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) = 114.91, 116.47 (d, JC-F = 22.0 Hz), 129.82 (d, JC-F = 8.9 Hz), 131.37, 160.06, 162.07, 162.25 (d, JC-F = 253.3 Hz), 166.62; HRMS (ESI+) m/z calc. for C10H7N2ClF [M + H]+ 209.0276, found 209.0278; HPLC tR = 6.44 min; Rf = 0.31 (EtOAc/n-Hex, 1:3, v/v).
2-chloro-4-(naphthalen-2-yl)pyrimidine (37): Yield: 87%; white solid; Mp 114–116 °C;
1H NMR (400 MHz, CDCl
3): δ (ppm) = 7.54–7.62 (m, 2H), 7.79 (d,
J = 5.3 Hz, 1H), 7.88–7.92 (m, 1H), 7.95–8.01 (m, 2H), 8.15 (dd,
J1 = 1.9 Hz,
J2 = 8.6 Hz, 1H), 8.65–8.67 (m, 1H), 8.68 (d,
J = 5.3 Hz, 1H);
13C NMR (100 MHz, CDCl
3): δ (ppm) = 115.49, 123.78, 127.08, 127.95, 128.19, 128.40, 129.17, 129.38, 132.42, 133.26, 135.17, 160.01, 162.10, 167.27; HRMS (ESI+)
m/z calc. for C
14H
10N
2Cl [M + H]
+ 241.0527, found 241.0528 as reported [
50]; HPLC
tR = 7.31 min; Rf = 0.28 (EtOAc/n-Hex, 1:3,
v/v).
2-chloro-4-(furan-2-yl)pyrimidine (38): Yield: 50%; white solid; Mp 67–69 °C;
1H NMR (400 MHz, CDCl
3): δ (ppm) = 6.61 (dd,
J1 = 1.7 Hz,
J2 = 3.5 Hz, 1H), 7.39 (dd,
J1 = 0.7 Hz,
J2 = 3.5 Hz, 1H), 7.53 (d,
J = 5.2 Hz, 1H), 7.63 (dd,
J1 = 0.7 Hz,
J2 = 1.7 Hz, 1H), 8.58 (d,
J = 5.2 Hz, 1H) as reported [
51];
13C NMR (100 MHz, CDCl
3): δ (ppm) = 113.10, 113.13, 114.58, 146.24, 150.52, 158.11, 159.92, 161.76; HRMS (ESI+)
m/z calc. for C
8H
6ON
2Cl [M + H]
+ 181.0163, found 181.0163; HPLC
tR = 5.03 min; Rf = 0.27 (EtOAc/n-Hex; 1:4,
v/v).
2-chloro-4-(furan-3-yl)pyrimidine (39): Yield: 66%; grey solid; Mp 62–64 °C (lit. 87–89 °C [
52]);
1H NMR (400 MHz, CDCl
3): δ (ppm) = 6.90 (dd,
J1 = 0.9 Hz,
J2 = 1.9 Hz, 1H), 7.32 (d,
J = 5.1 Hz, 1H), 7.52–7.55 (m, 1H), 8.21–8.23 (m, 1H), 8.55 (d,
J = 5.2 Hz, 1H);
13C NMR (100 MHz, CDCl
3): δ (ppm) = 108.36, 115.06, 124.41, 144.77, 144.88, 159.67, 161.91, 161.98; HRMS (ESI+)
m/z calc. for C
8H
6ON
2Cl [M + H]
+ 181.0163, found 181.0161; HPLC
tR = 5.29 min; Rf = 0.18 (EtOAc/n-Hex, 1:4,
v/v).
2-bromo-4-phenylpyrimidine (40): Yield: 48%; white solid; Mp 68–70 °C (lit. 85–87 °C [
20];
1H NMR (400 MHz, CDCl
3): δ (ppm) = 7.49–7.55 (m, 3H), 7.69 (d,
J = 5.3 Hz, 1H), 8.07–8.10 (m, 2H), 8.57 (d,
J = 5.3 Hz, 1H);
13C NMR (100 MHz, CDCl
3): δ (ppm) = 115.67, 127.58, 129.28, 132.08, 135.13, 153.79, 159.73, 167.13; HRMS (ESI+)
m/z calc. for C
10H
7BrN
2 [M + H]
+ 234.9865, found 234.9869; HPLC
tR = 6.45 min; Rf = 0.38 (EtOAc/n-Hex, 1:2,
v/v).
2-chloro-4-phenyl-6-(trifluoromethyl)pyrimidine (41): Yield: 27%; pale yellow solid; Mp 47–49 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) = 7.54–7.63 (m, 3H), 7.96 (s, 1H), 8.15–8.18 (m, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) = 100.13, 111.06, 120.08 (q, JC-F = 274.1 Hz), 127.93, 129.55, 133.14, 133.78, 134.25, 169.84; HRMS (ESI+) m/z calc. for C11H7N2ClF3 [M + H]+ 259.0244, found 259.0250; HPLC tR = 7.51 min; Rf = 0.60 (EtOAc/n-Hex, 1:4, v/v).
2-chloro-6-phenylpyrimidine-4-carboxylic acid (42): Yield: 92%; appearance; Mp > 300 °C; 1H NMR (400 MHz, DMSO-d6): δ (ppm) = 7.51–7.58 (m, 3H), 8.13–8.16 (m, 2H), 8.29 (s, 1H), 1H from COOH is exchanged; 13C NMR (100 MHz, DMSO-d6): δ (ppm) = 114.06, 127.24, 129.17, 131.80, 134.90, 160.30, 165.40, 166.62, 168.53; HRMS (ESI–) m/z calc. for C11H6O2N2Cl [M − H ]– 233.0123, found 233.0121; HPLC tR = 5.29 min; Rf = 0.04 (DCM/MeOH, 9:1, v/v)
2-chloro-4-methyl-6-phenylpyrimidine (43): Yield: 78%; pale orange solid; Mp 42–44 °C;
1H NMR (400 MHz, CDCl
3): δ (ppm) = 2.60 (s, 3H), 7.48–7.55 (m, 4H), 8.06–8.08 (m, 2H) as reported [
53];
13C NMR (100 MHz, CDCl
3): δ (ppm) = 24.37, 100.13, 114.87, 127.55, 129.19, 131.75, 135.49, 166.96, 170.98; HRMS (ESI+)
m/z calc. for C
11H
10N
2Cl [M + H]
+ 205.0527, found 205.0528; HPLC
tR = 6.60 min; Rf = 0.41 (EtOAc/n-Hex, 1:2,
v/v).
2-chloro-4-methoxy-6-phenylpyrimidine (44A): Yield: 34%; white solid; Mp 88–90 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) = 4.05 (s, 3H), 7.03 (s, 1H), 7.47–7.51 (m, 3H), 8.00–8.03 (m, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) = 54.87, 102.05, 127.36, 129.06, 131.38, 135.62, 160.45, 167.10, 171.87; HRMS (ESI+) m/z calc. for C11H10ON2Cl [M + H]+ 221.0476, found 221.0477; HPLC tR = 7.41 min; Rf = 0.62 (EtOAc/n-Hex, 1:2, v/v).
4-chloro-6-methoxy-2-phenylpyrimidine (44B): Yield: 36%; white solid; Mp 49–51 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) = 4.11 (s, 3H), 6.66 (s, 1H), 7.47–7.54 (m, 3H), 8.42–8.46 (m, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) = 54.44, 105.24, 128.62, 128.67, 131.59, 136.35, 161.10, 164.79, 170.77; HRMS (ESI+) m/z calc. for C11H10ON2Cl [M + H]+ 221.0476, found 221.0475; HPLC tR = 7.96 min; Rf = 0.65 (EtOAc/n-Hex, 1:2, v/v).
2-chloro-6-phenylpyrimidin-4-amine (45): Yield: 84%; pale yellow solid; Mp 160–162 °C; 1H NMR (400 MHz, CDCl3): δ (ppm) = 5.39 (s, 2H), 6.72 (s, 1H), 7.44–7.48 (m, 3H), 7.94–7.96 (m, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm) = 98.87, 127.20, 128.94, 131.05, 136.12, 161.13, 165.10, 166.03; HRMS (ESI+) m/z calc. for C10H9N3Cl [M + H]+ 206.0480, found 206.0477; HPLC tR = 5.25 min; Rf = 0.43 (EtOAc/n-Hex, 1:1, v/v).
2-chloro-4-phenylquinazoline (46): Yield: 54%; white solid; Mp 91–92 °C (lit. 112–114 °C [
41]);
1H NMR (400 MHz, DMSO-
d6): δ (ppm) = 7.56–7.61 (m, 3H), 7.63 (ddd,
J1 = 1.2 Hz,
J2= 6.9 Hz,
J3 = 8.3 Hz, 1H), 7.77–7.82 (m, 2H), 7.95 (ddd,
J1 = 1.4 Hz,
J2 = 6.9 Hz,
J3 = 8.4 Hz, 1H), 8.06 (ddd,
J1 = 0.7 Hz,
J2 = 1.2 Hz,
J3 = 8.5 Hz, 1H), 8.14 (ddd,
J1 = 0.7 Hz,
J2 = 1.4 Hz,
J3 = 8.4 Hz, 1H);
13C NMR (100 MHz, DMSO-
d6): δ (ppm) = 121.76, 127.64, 128.14, 128.26, 128.90, 130.28, 130.84, 135.02, 136.04, 153.16, 157.18, 171.84; HRMS (ESI+)
m/z calc. for C
14H
10N
2Cl [M + H]
+ 241.0527, found 241.0523; HPLC
tR = 7.08 min; Rf = 0.29 (EtOAc/n-Hex, 1:5,
v/v).