5134
A. E. Thompson et al. / Tetrahedron 61 (2005) 5131–5135
as a white solid (260 mg, 82%) mp 70.9–71.6 8C; ymax(KBr)
3054, 2988, 2952, 1568, 1546, 1450 cmK1 1H NMR
15 as a crystalline solid (258 mg, 75%) mp 138.6–139.0 8C;
1
;
y
max(KBr) 3466, 3299, 3151, 2975, 1639 cmK1; H NMR
(400 MHz, acetone-d6) d 8.79 (2H, s), 8.17 (1H, dd, JZ
1.6, 4.8 Hz), 7.82 (1H, dd, JZ1.6, 7.2 Hz), 7.06 (1H, dd, JZ
4.8, 7.2 Hz), 4.42 (2H, q, JZ7.2 Hz), 3.98 (3H, s), 1.34 (3H,
t, JZ7.2 Hz); 13C NMR (100 MHz, CDCl3) d 164.70,
160.42, 158.80, 146.80, 137.38, 124.10, 117.69, 116.91,
96.11, 61.99, 54.82, 14.57; MS (EI) m/z 231.1 (MC, 100%).
Anal. Calcd. for C12H13N3O2: C, 62.33; H, 5.67; N, 18.17.
Found: C, 62.42; H, 5.74; N, 17.93%.
(400 MHz, DMSO-d6) d 8.10 (1H, dd, JZ2.0, 4.8 Hz), 7.47
(1H, dd, JZ2.0, 7.2 Hz), 7.12 (1H, d, JZ8.4 Hz), 6.99 (1H,
dd, JZ4.8, 7.2 Hz), 6.30 (1H, d, JZ8.4 Hz), 5.88 (2H, br s,
NH2), 4.29 (2H, q, JZ7.2 Hz), 2.05 (3H, s), 1.22 (3H, t, JZ
7.2 Hz); 13C NMR (100 MHz, DMSO-d6) d 160.2, 158.5,
153.6, 145.3, 139.6, 139.0, 123.3, 119.0, 116.8, 104.9, 60.9,
22.3, 14.5; MS (EI) m/z 229.1 (MC, 100%). Anal. Calcd. for
C13H15N3O: C, 68.10; H, 6.59; N, 18.23. Found: C, 67.85;
H, 6.54; N, 17.96%.
4.2.2. 5-(2-Ethoxy-3-pyridyl)pyrimidine (12). Boronic
4
acid
2
(284 mg, 1.7 mmol), 5-bromopyrimidine
4.2.6. N-(20-Ethoxy-2-methyl-[3,30]bipyridinyl-6-yl)-
acetamide (16). Boronic acid 2 (284 mg, 1.7 mmol),
N-(5-bromo-6-methyl-pyridin-2-yl)-acetamide 815 (334 mg,
1.5 mmol), Pd(PPh3)2Cl2 (59.6 mg, 0.085 mmol), 1,4-diox-
ane (10 mL) and Na2CO3 (4 mL); reaction time 24 h; eluent
EtOAc, gave 16 as a crystalline solid (317 mg, 78%) mp
147.7–148.6 8C; ymax(KBr) 3241, 3042, 2981, 1669, 1577,
(239 mg, 1.5 mmol), Pd(PPh3)2Cl2 (59.6 mg, 0.085 mmol),
1,4-dioxane (10 mL) and Na2CO3 (4 mL); reaction time
24 h; eluent EtOAc:hexane (1:1 v/v), gave 12 as a white
solid (271 mg, 90%) mp 119.0–119.8 8C; ymax(KBr) 2992,
2966, 2908, 1579, 1555, 1439 cmK1;1H NMR (400 MHz,
acetone-d6) d 9.10 (1H, s), 9.01 (2H, s), 8.23 (1H, dd, JZ
1.6, 4.8 Hz), 7.89 (1H, dd, JZ1.6, 8.0 Hz), 7.11 (1H, dd, JZ
5.2, 7.6 Hz), 4.43 (2H, q, JZ7.2 Hz), 1.34 (3H, t, JZ
6.8 Hz); 13C NMR (100 MHz, CDCl3) d 160.5, 157.3,
156.4, 147.7, 138.0, 130.6, 117.5, 117.0, 96.2, 62.2, 14.6;
MS (EI) m/z 201.1 (MC, 100%). Anal. Calcd. for
C11H11N3O: C, 65.66; H, 5.51; N, 20.88. Found: C, 65.46;
H, 5.51; N, 20.63%.
1
1533 cmK1; H NMR (400 MHz, DMSO-d6) d 10.50 (1H,
br s, NH), 8.17 (1H, dd, JZ2.0, 4.8 Hz), 7.94 (1H, d, JZ
8.4 Hz), 7.57 (1H, dd, JZ2.0, 7.2 Hz), 7.51 (1H, d, JZ
8.4 Hz), 7.04 (1H, dd, JZ4.8, 7.2 Hz), 4.31 (2H, q, JZ
7.2 Hz), 2.20 (3H, s), 2.08 (3H, s), 1.20 (3H, t, JZ7.2 Hz);
13C NMR (100 MHz, DMSO-d6) d 169.2, 160.0, 154.3,
150.7, 146.3, 139.7, 139.6, 126.7, 122.0, 116.9, 110.4, 61.1,
23.3, 22.1, 14.4; MS (EI) m/z 271.0 (MC, 100%). Anal.
Calcd. for C15H17N3O2: C, 66.40; H, 6.32; N, 15.49. Found:
C, 66.18; H, 6.25; N, 15.31%.
4.2.3. 2-(2-Ethoxy-3-pyridyl)pyrimidine (13). Boronic
2 (284 mg, 1.7 mmol), 2-bromopyrimidine 5
acid
(239 mg, 1.5 mmol), Pd(PPh3)2Cl2 (59.6 mg, 0.085 mmol),
1,4-dioxane (10 mL) and Na2CO3 (4 mL); reaction time
24 h; eluent EtOAc:hexane (1:2 v/v), gave 13 as a colour-
less viscous oil (268 mg, 89%); ymax(KBr) 2977, 1571,
1445, 1415 cmK1; 1H NMR (200 MHz, CDCl3) d 8.68 (2H,
d, JZ4.8 Hz), 8.11 (1H, d, JZ4.8 Hz), 7.94 (1H, d, JZ
7.3 Hz), 7.03 (1H, t, JZ4.8 Hz), 6.83 (1H, dd, JZ5.1,
7.2 Hz), 4.37 (2H, q, JZ7.0 Hz), 1.23 (3H, t, JZ7.0 Hz);
13C NMR (100 MHz, CDCl3) d 164.5, 161.1, 156.8 (2C),
148.0, 140.1, 122.3, 118.7, 116.3, 62.0, 14.2; HRMS (EI)
calcd for C11H11N3O (MC) 201.09121, found 201.09133.
4.2.7. Methyl 2-amino-5-(2-ethoxy-3-pyridyl)-3-pyra-
zinoate (17). Boronic acid 2 (284 mg, 1.7 mmol),
3-amino-6-bromopyrazine-2-carboxylic acid methyl ester
9a16 (345 mg, 1.5 mmol), Pd(PPh3)2Cl2 (59.6 mg,
0.085 mmol), 1,4-dioxane (10 mL) and Na2CO3 (4 mL);
reaction time 16 h at 20 8C; eluent EtOAc, gave 17 as a
yellow solid (440 mg, 90%) mp 156.6–157.0 8C; ymax(KBr)
3447, 3264, 3146, 2979, 1693, 1618 cmK1 1H NMR
;
(400 MHz, DMSO-d6) d 8.89 (1H, s), 8.17 (1H, dd, JZ2.0,
4.8 Hz), 8.12 (1H, dd, JZ2.0, 7.6 Hz), 7.46 (2H, br s, NH2),
7.11 (1H, dd, JZ4.8, 7.6 Hz), 4.41 (2H, q, JZ7.2 Hz), 3.87
(3H, s), 1.35 (3H, t, JZ7.2 Hz); 13C NMR (100 MHz,
DMSO-d6) d 166.3, 159.8, 154.3, 148.0, 146.5, 138.0,
136.7, 122.4, 119.3, 117.4, 61.6, 52.2, 14.4; MS (EI) m/z
274.0 (MC, 100%). Anal. Calcd. for C13H14N4O3: C, 56.93;
H, 5.14; N, 20.43. Found: C, 56.63; H, 4.97; N, 20.33%.
4.2.4. 20-Ethoxy-5-nitro-[3,30]bipyridinyl-6-ylamine (14).
Boronic acid 2 (284 mg, 1.7 mmol), 5-bromo-2-amino-3-
nitropyridine
6 (327 mg, 1.5 mmol), Pd(PPh3)2Cl2
(59.6 mg, 0.085 mmol), 1,4-dioxane (10 mL) and Na2CO3
(4 mL); reaction time 24 h; eluent EtOAc, gave 14 as a
yellow solid (289 mg, 74%) mp 193.0–193.9 8C; ymax(KBr)
3470, 3275, 3121, 2984, 1654, 1561, 1351 cmK1; 1H NMR
(400 MHz, DMSO-d6) d 8.67 (1H, d, JZ2.0 Hz), 8.63 (1H,
d, JZ2.0 Hz), 8.15 (1H, dd, JZ2.0 Hz, JZ4.8 Hz), 8.03
(2H, br s, NH2), 7.90 (1H, dd, JZ2.0, 4.8 Hz), 7.07 (1H, dd,
JZ4.8, 7.6 Hz), 4.37 (2H, q, JZ7.2 Hz), 1.31 (3H, t, JZ
7.2 Hz); 13C NMR (100 MHz, DMSO-d6) d 159.7, 156.0,
152.7, 146.0, 137.9, 134.2, 126.2, 120.5, 118.7, 117.4, 61.5,
14.3; MS (EI) m/z 260.0 (MC, 100%). Anal. Calcd. for
C12H12N4O3: C, 55.38; H, 4.65; N, 21.53. Found: C, 55.12;
H, 4.58; N, 21.36%.
When the reaction was carried out at reflux for 15 min,
product 17 (321 mg, 78% yield) was obtained.
A comparable reaction with 3-amino-6-chloropyrazine-2-
carboxylic acid methyl ester 9b,16 15 min at 60 8C, gave 17
in 62% yield.
4.2.8. 3-(2-Amino-4-trifluoromethylbenzene)-2-ethoxy-
pyridine (18). Boronic acid 2 (284 mg, 1.7 mmol),
1-amino-2-bromo-5-(trifluoromethyl)benzene 10 (360 mg,
1.5 mmol), Pd(PPh3)2Cl2 (59.6 mg, 0.085 mmol), 1,4-diox-
ane (10 mL) and Na2CO3 (4 mL); reaction time 24 h; eluent
4.2.5. 20-Ethoxy-5-methyl-[3,30]bipyridinyl-6-ylamine
(15). Boronic acid 2 (284 mg, 1.7 mmol), 6-amino-3-
bromo-2-methylpyridine 7 (281 mg, 1.5 mmol), Pd(PPh3)2-
Cl2 (59.6 mg, 0.085 mmol), 1,4-dioxane (10 mL) and
Na2CO3 (4 mL); reaction time 24 h; eluent EtOAc, gave
DCM, gave 18 as a clear brown oil (300 mg, 71%);
y
1
max(KBr) 3464, 3378, 3054, 2982, 1633, 1579 cmK1; H
NMR (400 MHz, acetone-d6) d 8.27 (1H, dd, JZ2.0,
3.2 Hz), 7.70 (1H, dd, JZ2.0, 5.2 Hz), 7.26 (1H, d, JZ