hexane, 1 : 1 (v/v) gave compound 10 as a white solid
(83% yield) mp 181–182 ЊC. H NMR (CDCl3) δ 9.09 (d, 1 H,
4,6-Bis(2-methoxy-3-pyridyl)pyrimidine (18)
1
2-Methoxy-3-pyridylboronic acid 1713i (200 mg, 1.32 mmol),
4,6-dichloropyrimidine 12 (87 mg, 0.58 mmol), Pd(PPh3)2Cl2
(46 mg, 0.07 mmol) and Na2CO3 (2 cm3) in dioxane (5 cm3) were
reacted according to the general procedure. Eluent EtOAc–
hexane 1 : 5 (v/v) gave compound 18 as a white solid (110 mg,
64%) mp 115–116 ЊC. 1H NMR (CDCl3) δ 9.31 (s, 1 H), 8.83 (s,
1 H), 8.48 (m, 2 H), 8.30 (m, 2 H), 7.09 (m, 2 H), 4.11 (s, 6 H);
13C NMR (CDCl3) δ 161.70, 161.09, 158.55, 148.71, 139.69,
121.09, 120.69, 117.51, 53.72; m/z (EI) = 294 (Mϩ, 100%). Anal.
calc. for C16H14N4O2: C, 65.30; H, 4.79; N, 19.04. Found: C,
65.37; H, 4.90; N, 18.71%. Crystals for X-ray analysis were
grown from ethanol.
J = 2.3 Hz), 8.86 (s, 2 H), 8.27 (d, 1 H, J = 2.3 Hz), 8.14 (d, 1 H,
J = 8.3 Hz), 7.89 (d, 1 H, J = 8.3 Hz), 7.77 (m, 1 H), 7.62 (m,
1 H), 4.10 (s, 3 H); 13C NMR (CDCl3) δ 165.50, 157.65 (2C),
148.56, 147.69, 133.03, 130.08, 129.42, 127.95, 127.77, 127.55,
127.46, 125.42, 55.27; m/z (EI) = 237 (Mϩ, 100%). Anal. calc.
for C14H11N3O: C, 70.87; H, 4.67; N, 17.71. Found: C, 70.36; H,
4.82; N, 17.69%.
2-Methoxy-5-(2-pyrimidyl)pyrimidine (11)
2-Methoxy-5-pyrimidylboronic acid 4, 2-bromopyrimidine,
Pd(PPh3)2Cl2 and Na2CO3 in dioxane; eluent EtOAc–petroleum
ether, 1 : 2 (v/v) gave compound 11 as a white solid (4% yield)
mp 149–150 ЊC. 1H NMR (CDCl3) δ 9.48 (s, 2 H), 8.78 (d, 2 H,
J = 4.8 Hz), 7.22 (t, 1 H, J = 4.8 Hz), 4.09 (s, 3 H); 13C NMR
(CDCl3) δ 166.70, 161.34, 159.57, 157.39, 125.14, 119.65, 55.33;
m/z (EI) = 188 (Mϩ, 98%), 173 (100%). Anal. calc. for
C9H8N4O: C, 57.44; H, 4.28; N, 29.77. Found: C, 57.77; H, 4.56;
N, 29.88%. The analogous reaction of 2-chloropyrimidine gave
11 in 50% yield.
4-Chloro-6-(2-methoxy-3-pyridyl)pyrimidine (19)
Following the procedure above for the preparation of 18 [using
12 (870 mg, 5.81 mmol), 17 (2.00 g, 13.18 mmol), Pd(PPh3)2Cl2
(460 mg, 0.66 mmol), dioxane (15 cm3) and Na2CO3 solution
(6 cm3)] and quenching the reaction before it had gone to com-
pletion (as judged by TLC monitoring) gave compound 19 as
the first product eluted, followed by compound 18 (706 mg,
41% yield). Compound 19, a white solid (260 mg, 20%) mp
4,6-Bis(2-methoxy-5-pyridyl)pyrimidine (14)
1
97–98 ЊC. H NMR (CDCl3) δ 9.01 (s, 1 H), 8.57 (m, 1 H),
2-Methoxy-5-pyridylboronic acid 1310 (1.032 g, 6.79 mmol),
4,6-dichloropyrimidine 12 (461 mg, 3.00 mmol), Pd(PPh3)2Cl2
(238 mg, 0.34 mmol) and Na2CO3 (8 cm3) in dioxane (10 cm3);
eluent EtOAc–hexane, 1 : 5 (v/v) gave compound 14 as a white
8.25 (m, 1 H), 8.19 (m, 1 H), 7.10 (m, 1 H), 4.17 (s, 3 H);
13C NMR (CDCl3) δ 162.20, 162.01, 159.20, 150.00, 140.64,
122.01, 119.55, 118.03, 117.02, 54.22; m/z (EI)
= 221
(Mϩ, 100%). Anal. calc. for C10H8ClN3O: C, 54.19; H, 3.64; N,
18.96. Found: C, 54.28; H, 3.63; N, 19.04%. [For analytically-
pure samples of 19 additional unassigned peaks of low inten-
1
solid (740 mg, 84%) mp 149–150 ЊC. H NMR (CDCl3) δ 9.19
(s, 1 H), 8.88 (s, 2 H), 8.30 (d, 2 H, J = 8.7 Hz), 7.89 (s, 1 H), 6.84
(d, 2 H, J = 8.7 Hz), 3.99 (s, 6 H); 13C NMR (CDCl3) δ 165.91,
162.30, 159.27, 146.51 (2 C), 137.25 (2 C), 126.02, 111.27 (2 C),
110.63, 53.90 (2 C); m/z (EI) = 294 (Mϩ, 100%). Anal. calcd for
C16H14N4O4: C, 65.30; H, 4.80; N, 19.04. Found: C, 65.48; H,
4.90; N, 18.74%.
1
sity were always present in the H NMR spectra: δ 8.18 (m),
7.60 (m), 6.96 (m)].
4-(2-Methoxy-5-pyridyl)-6-(2-methoxy-3-pyridyl)pyrimidine
(20)
The same reaction using 4,6-diiodopyrimidine (prepared in
81% yield from 12)26 gave 14 in 82% yield.
2-Methoxy-5-pyridylboronic acid 13 (109 mg, 0.72 mmol),
compound 19 (140 mg, 0.63 mmol), Pd(PPh3)2Cl2 (25 mg, 0.04
mmol) and Na2CO3 solution (3 cm3) in dioxane (10 cm3) were
reacted according to the general procedure. Eluent EtOAc–
hexane 1 : 10 (v/v) gave compound 20 as a white solid (180 mg,
97%) mp 125–126 ЊC. 1H NMR (CDCl3) δ 9.25 (s, 1 H), 8.91 (s,
1 H), 8.51 (d, 1 H, J = 7.6 Hz), 8.45 (s, 1 H), 8.36 (d, 1 H, J =
8.7 Hz), 8.29 (m, 1 H), 7.08 (m, 1 H), 6.88 (d, 1 H, J = 8.7 Hz),
4.09 (s, 3 H), 4.01 (s, 3 H); 13C NMR (CDCl3) δ 165.84, 161.86,
161.65, 161.28, 158.87, 148.86, 146.56, 139.63, 137.45, 126.37,
120.21, 117.54, 115.92, 111.31, 53.86; m/z (EI) = 294 (Mϩ,
100%). Anal. calc. for C16H14N4O2: C, 65.30; H, 4.49; N, 19.04.
Found: C, 65.55; H, 4.53; N, 19.38%.
4,6-Bis(2-chloro-5-pyridyl)pyrimidine (15)
Phosphoryl chloride (782 mg, 5.10 mmol) was added dropwise
to a stirred solution of compound 14 (150 mg, 0.51 mmol) in
dry DMF (10 cm3) at 0 ЊC. Stirring was continued for 1 h then
the mixture was heated at 110 ЊC for 19 h, then cooled to 0 ЊC
and quenched with saturated sodium acetate solution (25 cm3).
The mixture was extracted with EtOAc (4 × 50 cm3). The
organic layer was then washed with water (3 × 100 cm3) and was
dried over MgSO4. The residue was chromatographed through
a silica gel column, eluent EtOAc–hexane 1 : 2 (v/v) to give
compound 15 as a white solid (98 mg, 63%) mp 233–234 ЊC.
1H NMR (CDCl3) δ 9.37 (s, 1 H), 9.13 (s, 2 H), 8.45 (d, 2 H,
J = 8.3 Hz), 8.09 (s, 1 H), 7.53 (d, 2 H, J = 8.3 Hz); 13C NMR
(CDCl3) δ 161.78, 159.72, 154.23, 148.51, 137.37, 131.19,
124.77, 112.34; m/z (EI) = 302 (Mϩ, 100%). Anal. calc. for
C14H8Cl2N4: C, 55.47; H, 2.66; N, 18.48. Found: C, 55.27; H,
2.93; N, 18.50.
Crystallographic studies
X-Ray diffraction experiments (Table 2) were carried out on a
SMART 3-circle diffractometer with a 6K CCD area detector,
using graphite-monochromated Mo–Kα radiation (λ = 0.71073
Å) and a Cryostream (Oxford Cryosystems) open-flow N2
cryostat. The structures were solved by direct methods and
refined by full-matrix least squares against F 2 of all data,
using SHELXTL software.27 Full crystallographic data, exclud-
ing structure factors, have been deposited at the Cambridge
Crystallographic Data Centre. CCDC reference numbers
b314624n/ for crystallographic data in.cif or other electronic
format.
4,6-Bis[2-(4-tert-butyl)phenyl-5-pyridyl]pyrimidine (16)
4-(tert-Butyl)phenylboronic acid (154 mg, 0.87 mmol), com-
pound 15 (116 mg, 0.38 mmol), Pd(PPh3)2Cl2 (30 mg, 0.04
mmol) and Na2CO3 (3 cm3) in dioxane (10 cm3) were reacted
according to the general procedure. Elution with EtOAc–hex-
ane 1 : 10 (v/v) gave compound 16 as a white solid (30 mg, 16%)
mp 274–276 ЊC. 1H NMR (CDCl3) δ 9.42 (s, 2 H), 9.37 (s, 1 H),
8.53 (d, 2 H, J = 8.3 Hz), 8.19 (s, 1 H), 8.05 (d, 4 H, J = 8.6 Hz),
7.90 (d, 2 H, J = 8.3 Hz), 7.55 (d, 4 H, J = 8.3 Hz), 1.38 (s, 18 H);
13C NMR (CDCl3) δ 162.56, 159.61, 159.49, 153.12, 148.43,
135.61, 135.39, 130.35, 126.91, 125.91, 120.18, 112.13, 34.81,
31.27; m/z (EI) = 498 (Mϩ, 100%). Anal. calc. for C34H34N4: C,
81.89; H, 6.87; N, 11.24. Found: C, 57.00; H, 6.18; N, 17.29%.
Acknowledgements
We thank Dr P. R. Parry (Seal Sands Chemicals Ltd.) for help-
ful discussions, and A. Thompson for performing the reactions
of 2-chloropyrimidine in Table 1.
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 8 5 2 – 8 5 7
856