Z. Liu et al. / Tetrahedron 63 (2007) 1931–1936
1935
1
8.14–8.12 (m, 2H), 7.56–7.53 (m, 3H), 2.74 (t, J¼6.9 Hz,
2H), 2.57 (t, J¼7.2 Hz, 2H), 2.56 (s, 3H), 2.05–1.96 (m,
2H); 13C NMR (100 MHz, CDCl3): d 168.5, 164.4, 154.1,
132.2, 131.6, 128.8, 128.0, 119.1, 108.1, 97.9, 75.3, 24.7,
23.7, 19.0, 16.2; LRMS (EI) m/z 278 ([M+1]+), 277 (100,
M+), 223; HRMS (EI) calcd for C17H15N3O (M+):
277.1215, found 277.1211.
186 ꢀC; H NMR (300 MHz, CDCl3): d 8.17 (d, J¼8.4 Hz,
2H), 7.52 (d, J¼8.4 Hz, 2H), 7.39 (d, J¼8.4 Hz, 2H), 7.09
(d, J¼8.4 Hz, 2H), 3.97 (s, 3H), 2.81 (s, 3H), 2.32 (s, 3H),
2.28 (s, 3H); 13C NMR (100 MHz, CDCl3): d 166.6, 165.6,
163.0, 160.8, 149.7, 139.5, 137.7, 130.5, 130.3, 129.3,
126.8, 126.0, 116.1, 113.9, 52.3, 25.7, 21.8, 21.3; LRMS
(EI) m/z 373 ([M+1]+), 372 (100, M+), 238, 119; HRMS
(EI) calcd for C23H20N2O3 (M+): 372.1474, found 372.1475.
4.4.9. 6-Methyl-5-(3,3-dimethylbut-1-ynyl)-2-phenylpyr-
imidin-4-ol (6i). Yield: 65%; white solid; mp 199–201 ꢀC;
1H NMR (300 MHz, CDCl3): d 8.27–8.24 (m, 2H), 7.55–
7.52 (m, 3H), 2.56 (s, 3H), 1.39 (s, 9H); 13C NMR
(100 MHz, CDCl3): d 168.0, 164.5, 153.7, 131.8, 128.7,
128.0, 109.5, 108.7, 71.9, 31.1, 28.6, 23.6; LRMS (EI) m/z
266 (50, M+), 251 (100); HRMS (EI) calcd for C17H18N2O
(M+): 266.1419, found 266.1423.
4.5.5. 6-(2-Fluorophenyl)-5-(4-methoxyphenyl)-2,4-di-
methylfuro[2,3-d]pyrimidine (9e). Yield: 75%; colorless
oil; H NMR (300 MHz, CDCl3): d 7.51–7.45 (m, 1H),
1
7.41–7.33 (m, 1H), 7.29–7.27 (m, 2H), 7.17–7.08 (m, 2H),
6.95 (d, J¼6.9 Hz, 2H), 3.88 (s, 3H), 2.83 (s, 3H), 2.44 (s,
3H); 13C NMR (100 MHz, CDCl3): d 166.3, 163.1, 161.6,
1
159.7 (d, JC–F¼252.8 Hz), 159.5, 145.4, 131.2, 131.1 (d,
4JC–F¼3.6 Hz), 131.0, 124.0, 123.8, 118.4, 117.5 (d, 3JC–F
¼
2
4.5. General procedure for the synthesis of furo[2,3-d]-
pyrimidines 9
16.6 Hz), 116.3 (d, JC–F¼21.4 Hz), 115.5, 114.0, 55.2,
25.8, 22.1; LRMS (EI) m/z 348 (14, M+), 156, 86, 84
(100); HRMS (EI) calcd for C21H17FN2O2 (M+):
348.1274, found 348.1269.
To a solution of alkynylpyrimidinol (0.500 mmol), ArI
(1.00 mmol), bpy (0.100 mmol), Cs2CO3 (1.00 mmol), and
acetonitrile (20 mL) was added Pd2(dba)3 (0.025 mmol)
under N2 atmosphere. The reaction was stirred at 50 ꢀC for
24 h. The mixture was filtered and the solid phase was
washed with methanol (10 mL). The filtrate was concen-
trated and the residue was purified by flash column chroma-
tography to afford the corresponding product.
4.5.6. 5,6-Bis(4-methoxyphenyl)-2,4-dimethylfuro-
[2,3-d]pyrimidine (9f). Yield: 43%; white solid; mp 138–
141 ꢀC; 1H NMR (300 MHz, CDCl3): d 7.50 (d, J¼9.0 Hz,
2H), 7.32 (d, J¼9.0 Hz, 2H), 7.02 (d, J¼9.0 Hz, 2H), 6.81
(d, J¼9.0 Hz, 2H), 3.89 (s, 3H), 3.79 (s, 3H), 2.78 (s, 3H),
2.29 (s, 3H); 13C NMR (100 MHz, CDCl3): d 165.8, 162.3,
160.6, 160.0, 159.6, 149.4, 131.5, 128.2, 124.5, 122.0,
116.7, 114.5, 114.0, 113.5, 55.3, 55.2, 25.7, 21.6; LRMS
(EI) m/z 360 (40, M+), 254 (100), 239, 156, 84; HRMS
(EI) calcd for C22H20N2O3 (M+): 360.1474, found 360.1467.
4.5.1. 2,4-Dimethyl-5-phenyl-6-p-tolylfuro[2,3-d]pyrimi-
1
dine (9a). Yield: 57%; white solid; mp 103–106 ꢀC; H
NMR (300 MHz, CDCl3): d 7.51–7.48 (m, 3H), 7.45–7.40
(m, 4H), 7.09 (d, J¼8.4 Hz, 2H), 2.79 (s, 3H), 2.32 (s,
3H), 2.26 (s, 3H); 13C NMR (100 MHz, CDCl3): d 165.5,
162.6, 160.9, 149.3, 139.0, 132.6, 130.3, 129.2, 129.1,
128.4, 126.6, 126.4, 116.4, 114.8, 25.8, 21.7, 21.3; LRMS
(EI) m/z 315 ([M+1]+), 314 (100, M+), 173; HRMS (EI)
calcd for C21H18N2O (M+): 314.1419, found 314.1423.
4.5.7. 6-(4-(Trifluoromethyl)phenyl)-5-(4-methoxy-
phenyl)-2,4-dimethylfuro[2,3-d]pyrimidine (9g). Yield:
48%; white solid; mp 47–49 ꢀC; 1H NMR (300 MHz,
CDCl3): d 7.67 (d, J¼8.4 Hz, 2H), 7.54 (d, J¼8.7 Hz, 2H),
7.34 (d, J¼8.4 Hz, 2H), 7.05 (d, J¼8.7 Hz, 2H), 3.91 (s,
3H), 2.80 (s, 3H), 2.31 (s, 3H); 13C NMR (100 MHz,
CDCl3): d 166.1, 164.0, 162.4, 160.4, 147.9, 133.1, 131.5,
4.5.2. 5-(4-Methoxyphenyl)-2,4-dimethyl-6-p-tolyl-
furo[2,3-d]pyrimidine (9b). Yield: 70%; white solid; mp
133–136 ꢀC; 1H NMR (300 MHz, CDCl3): d 7.46 (d,
J¼8.1 Hz, 2H), 7.32 (d, J¼6.6 Hz, 2H), 7.09 (d, J¼8.1 Hz,
2H), 7.02 (d, J¼6.6 Hz, 2H), 3.90 (s, 3H), 2.79 (s, 3H),
2.32 (s, 3H), 2.30 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 165.5, 162.6, 161.0, 159.7, 158.4, 149.5, 139.0, 131.4,
129.2, 126.6, 124.4, 116.7, 114.5, 55.3, 25.7, 21.6, 21.3;
LRMS (EI) m/z 345 ([M+1]+), 344 (100, M+), 119; HRMS
(EI) calcd for C22H20N2O2 (M+): 344.1525, found 344.1531.
2
1
130.6 (q, JC–F¼32.8 Hz), 127.0, 125.8, 124.1 (q, JC–F
¼
270.5 Hz), 123.9, 117.8, 116.7, 115.2, 55.6, 26.2, 22.0;
LRMS (EI) m/z 399 ([M+1]+), 398 (100, M+), 173; HRMS
(EI) calcd for C22H17F3N2O2 (M+): 398.1242, found
398.1243.
4.5.8. 6-(2-Fluorophenyl)-5-(4-methoxyphenyl)-4-
methyl-2-phenylfuro[2,3-d]pyrimidine (9h). Yield: 75%;
white solid; mp 130–132 ꢀC; 1H NMR (300 MHz, CDCl3):
d 8.57–8.54 (m, 2H), 7.52–7.48 (m, 3H), 7.39–7.26 (m,
4H), 7.15–7.03 (m, 2H), 6.95 (d, J¼8.7 Hz, 2H), 3.86 (s,
3H), 2.51 (s, 3H); 13C NMR (100 MHz, CDCl3): d 166.6,
4.5.3. 2,4-Dimethyl-5-(thiophen-2-yl)-6-p-tolylfuro[2,3-d]-
pyrimidine (9c). Yield: 55%; white solid; mp 126–130 ꢀC;
1H NMR (300 MHz, CDCl3): d 7.55–7.52 (m, 3H),
7.21–7.18 (m, 1H), 7.16–7.14 (m, 2H), 7.13–7.12 (m, 1H),
2.80 (s, 3H), 2.37 (s, 3H), 2.34 (s, 3H); 13C NMR
(100 MHz, CDCl3): d 165.6, 163.2, 161.4, 151.6, 139.8,
132.6, 129.5, 129.4, 128.0, 127.9, 126.9, 126.1, 116.8,
107.3, 25.6, 21.2, 21.0; LRMS (EI) m/z 321 ([M+1]+), 320
(100, M+), 119, 91; HRMS (EI) calcd for C19H16N2OS
(M+): 320.0983, found 320.0990.
1
161.9, 159.9, 159.8 (d, JC–F¼253.2 Hz), 159.5, 146.2,
137.6, 131.2, 131.1, 131.0, 130.3, 128.5, 128.3, 124.0,
3
123.9, 118.8, 117.6 (d, JC–F¼13.6 Hz), 116.44, 116.39 (d,
2JC–F¼21.4 Hz), 114.0, 55.2, 22.5; LRMS (EI) m/z 411
([M+1]+), 410 (100, M+), 233, 123; HRMS (EI) calcd for
C26H19FN2O2 (M+): 410.1431, found 410.1388.
4.5.9. 5,6-Bis(4-methoxyphenyl)-4-methyl-2-phenyl-
furo[2,3-d]pyrimidine (9i). Yield: 49%; yellow solid; mp
145–146 ꢀC; 1H NMR (300 MHz, CDCl3): d 8.55–8.51
(m, 2H), 7.55 (d, J¼8.7 Hz, 2H), 7.50–7.48 (m, 3H), 7.37
4.5.4. Methyl 4-(2,4-dimethyl-6-p-tolylfuro[2,3-d]pyrim-
idin-5-yl)benzoate (9d). Yield: 36%; white solid; mp 184–