C. G. Hartung et al. / Tetrahedron 62 (2006) 10055–10064
10061
3.0 mL of DME, 0.4 mL of EtOH, and 0.6 mL of water. Flash
column chromatography (cHex/EtOAc 2:1) afforded 2c
(93 mg, 81%). Colorless solid; mp 139–140 ꢀC (EtOAc/
cHex), 1H NMR (200 MHz, DMSO-d6) d 3.89 (3H, s),
6.96–7.21 (3H, m), 7.28–7.51 (4H, m), 7.72 (2H, d,
J¼8.0 Hz), 7.96 (1H, d, J¼8.1 Hz), 8.70 (1H, s), 9.63 (1H,
br s); 13C NMR (66 MHz, DMSO-d6) d 55.6, 106.9, 112.0,
119.7, 120.5, 122.2, 125.8, 128.7, 130.1, 131.1, 139.9,
157.4, 157.7, 159.4, 160.3; HPLC purity 97%; ESIMS
m/z¼278 (MH+), 276 (MꢂHꢂ).
sodium carbonate (153 mg, 1.450 mmol, 3.50 equiv), and
Pd(PPh3)2Cl2 (6 mg, 2 mol %) were reacted in a mixture
of 3.0 mL of DME, 0.4 mL of EtOH, and 0.6 mL of water.
Flash column chromatography (cHex/EtOAc 4:1) afforded
2f (112 mg, 93%). Yellow solid; mp 156–157 ꢀC (EtOAc/
cHex); 1H NMR (200 MHz, DMSO-d6) d 7.05 (1H, t,
J¼7.3 Hz), 7.29–7.42 (3H, m), 7.72 (2H, d, J¼8.8 Hz),
7.83 (1H, t, J¼8.0 Hz), 8.25–8.48 (2H, m), 8.75 (1H, s),
8.80 (1H, s), 9.79 (1H, br s); 13C NMR (66 MHz, DMSO-
d6) d 102.7, 119.9, 120.9, 122.6, 124.7, 128.8, 130.5,
132.4, 138.4, 139.5, 148.2, 158.4, 158.5, 161.0; HPLC purity
95%; ESIMS m/z¼293 (MH+), 291 (MꢂHꢂ).
4.4.4. 1-[2-(6-Phenylamino-pyrimidin-4-yl)-phenyl]-
ethanone (2d). Following GM2, 1a (100 mg, 0.413 mmol),
2-acetylbenzeneboronic
acid
(85 mg,
0.516 mmol,
4.4.7. [6-(4-Methoxy-phenyl)-pyrimidin-4-yl]-phenyl-
amine (2g). Following GM2, 1a (100 mg, 0.413 mmol),
4-methoxybenzeneboronic acid (78 mg, 0.516 mmol,
1.25 equiv), sodium carbonate (153 mg, 1.450 mmol,
3.50 equiv), and Pd(PPh3)2Cl2 (6 mg, 2 mol %) were reacted
in a mixture of 3.0 mL of DME, 0.4 mL of EtOH, and
0.6 mL of water. Flash column chromatography (cHex/
EtOAc 4:1–3:1) afforded 2g (99 mg, 86%). Colorless solid;
mp 170–171 ꢀC (EtOAc/cHex); 1H NMR (200 MHz,
DMSO-d6) d 3.82 (3H, s), 6.96–7.12 (3H, m), 7.17 (1H, s),
7.34 (2H, t, J¼8.1 Hz), 7.71 (2H, d, J¼8.1 Hz), 7.99 (2H,
d, J¼8.8 Hz), 8.65 (1H, s), 9.63 (1H, br s); 13C NMR
(66 MHz, CDCl3) d 55.4, 98.5, 114.1, 122.4, 124.9, 128.4,
129.6, 129.7, 138.2, 158.7, 161.5, 161.6, 163.3; HPLC purity
99%; ESIMS m/z¼278 (MH+), 276 (MꢂHꢂ).
1.25 equiv), sodium carbonate (153 mg, 1.450 mmol,
3.50 equiv), and Pd(PPh3)2Cl2 (6 mg, 2 mol %) were reacted
in a mixture of 3.0 mL of DME, 0.4 mL of EtOH, and 0.6 mL
of water. Flash column chromatography (cHex/EtOAc 2:1)
afforded 2d (96 mg, 81%). Colorless solid; mp 129–130 ꢀC
(EtOAc/cHex); 1H NMR (200 MHz, DMSO-d6) d 2.33
(3H, s), 6.99–7.10 (2H, m), 7.35 (2H, t, J¼8.0 Hz), 7.54–
7.75 (6H, m), 8.61 (1H, s), 9.78 (1H, br s); 13C NMR
(66 MHz, DMSO-d6) d 30.3, 104.5, 120.0, 122.6, 127.3,
128.8, 129.5, 130.4, 136.6, 139.5, 141.4, 157.5, 160.7,
162.6, 202.7; HPLC purity 99%; ESIMS m/z¼290 (MH+),
288 (MꢂHꢂ).
4.4.5. [3-(6-Phenylamino-pyrimidin-4-yl)-phenyl]-meth-
anol (2e). Following GM2, 1a (100 mg, 0.413 mmol),
3-hydroxymethylbenzeneboronic acid (78 mg, 0.516 mmol,
1.25 equiv), sodium carbonate (153 mg, 1.450 mmol, 3.50
equiv), and Pd(PPh3)2Cl2 (6 mg, 2 mol %) were reacted in
a mixture of 3.0 mL of DME, 0.4 mL of EtOH, and 0.6 mL
of water. Flash column chromatography (cHex/EtOAc
1:1–1:3) afforded 2e (97 mg, 85%). Colorless solid; mp
4.4.8. (4-Methoxy-phenyl)-(6-phenyl-pyrimidin-4-yl)-
amine (2h) and (4-methoxy-phenyl)-(6-phenyl-pyrimi-
din-4-yl)-amine hydrochloride (2h$HCl). Method 1:
following GM1, 3a (100 mg, 0.525 mmol) and p-anisidine
(68 mg, 0.551 mmol, 1.05 equiv) were reacted in 1 mL of
2-propanol and 150 mL of concd HCl (37%) at 95 ꢀC. Filtra-
tion and drying gave 2h$HCl (130 mg, 79%). Yellow solid;
mp 261–262 ꢀC (EtOH/H2O); 1H NMR (200 MHz, DMSO-
d6) d 3.78 (3H, s), 7.01 (2H, d, J¼9.0 Hz), 7.40 (1H, s), 7.57–
7.69 (5H, m), 7.88–7.96 (2H, m), 8.85 (1H, s), 11.62 (1H, br
s); 13C NMR (66 MHz, DMSO-d6) d 55.3, 102.7, 114.2,
123.6, 127.2, 129.3, 130.0, 130.5, 132.1, 152.7, 153.3,
156.8, 161.2; ESIMS m/z¼278 (MH+); elemental analysis
calcd for C17H16ClN3O: C, 65.07; H, 5.14; N, 13.39; found:
C, 64.87; H, 5.23; N, 13.20.
1
161–162 ꢀC (EtOAc/cHex); H NMR (200 MHz, DMSO-
d6) d 4.60 (2H, d, J¼6.0 Hz), 5.34 (1H, t, J¼6.0 Hz), 7.03
(1H, t, J¼7.2 Hz), 7.24–7.54 (5H, m), 7.73 (2H, d,
J¼8.0 Hz), 7.90 (1H, d, J¼6.6 Hz), 8.03 (1H, s), 8.72 (1H,
s), 9.69 (1H, br s); 13C NMR (66 MHz, DMSO-d6) d 62.7,
101.9, 119.7, 122.3, 124.3, 124.7, 128.3, 128.6, 128.8,
136.7, 139.8, 143.2, 158.2, 161.0, 161.2; HPLC purity
97%; ESIMS m/z¼278 (MH+), 276 (MꢂHꢂ).
4.4.6. [6-(3-Nitro-phenyl)-pyrimidin-4-yl]-phenyl-amine
(2f) and [6-(3-nitro-phenyl)-pyrimidin-4-yl]-phenyl-
amine hydrochloride (2f$HCl). Method 1: following GM1,
3c (150 mg, 0.637 mmol) and aniline (61 mL, 0.669 mmol,
1.05 equiv) were reacted in 1.5 mL of 2-propanol and
150 mL of concd HCl (37%) at 95 ꢀC. Filtration gave 2f$HCl
(164 mg, 78%). Yellow solid; mp 276–277 ꢀC (EtOH/H2O);
1H NMR (200 MHz, DMSO-d6) d 7.13 (1H, t, J¼7.8 Hz),
7.33–7.45 (3H, m), 7.72 (2H, d, J¼8.0 Hz), 7.87 (1H, t,
J¼8.0 Hz), 8.35–8.45 (2H, m), 8.79 (1H, t, J¼1.8 Hz),
8.86 (1H, s), 10.52 (1H, br s); 13C NMR (66 MHz,
DMSO-d6) d 103.5, 120.8, 121.6, 123.9, 125.5, 129.0,
130.8, 133.1, 136.1, 138.5, 148.3, 155.7, 156.6, 161.2;
ESIMS m/z¼293 (MH+); elemental analysis calcd for
C16H13ClN4O2: C, 58.46; H, 3.99; N, 17.04. Found: C,
58.78; H, 4.02; N, 16.80.
Method 2: following GM2, 1d (100 mg, 0.368 mmol),
benzeneboronic acid (56 mg, 0.460 mmol, 1.25 equiv),
sodium carbonate (136 mg, 1.290 mmol, 3.50 equiv), and
Pd(PPh3)2Cl2 (5 mg, 2 mol %) were reacted in a mixture
of 3.0 mL of DME, 0.4 mL of EtOH, and 0.6 mL of water.
Flash column chromatography (cHex/EtOAc 4:1) afforded
2h (81 mg, 79%). Colorless solid; mp 152–153 ꢀC (EtOH);
1H NMR (200 MHz, DMSO-d6) d 3.74 (3H, s), 6.94 (2H,
d, J¼8.8 Hz), 7.12 (1H, s), 7.46–7.61 (5H, m), 7.95–8.04
(2H, m), 8.64 (1H, s), 9.50 (1H, br s); 13C NMR (66 MHz,
DMSO-d6) d 55.1, 101.1, 114.0, 122.0, 126.3, 128.8,
130.2, 132.5, 137.0, 155.0, 158.3, 160.9, 161.1; HPLC purity
96%; ESIMS m/z¼278 (MH+), 276 (MꢂHꢂ).
4.4.9. (4-Nitro-phenyl)-(6-phenyl-pyrimidin-4-yl)-amine
(2i) and (4-nitro-phenyl)-(6-phenyl-pyrimidin-4-yl)-
amine hydrochloride (2i$HCl). Method 1: following
GM1, 3a (100 mg, 0.525 mmol) and 4-nitroaniline (76 mg,
Method 2: following GM2, 1a (100 mg, 0.413 mmol), 3-
nitrobenzeneboronic acid (86 mg, 0.516 mmol, 1.25 equiv),