2
822
A. S. Karpov, T. J. J. Müller
PAPER
1
H NMR (CDCl , 300 MHz): = 1.19 (t, J = 7.2 Hz, 6 H), 3.30 (q,
Pyrimidines 7; General Procedure
In a screw cap pressure vessel Pd(PPh ) Cl (14.0 mg, 0.02 mmol)
3
J = 7.2 Hz, 4 H), 5.74 (d, J = 12.5 Hz, 1 H), 7.37–7.42 (m, 3 H),
3
2
2
7
.79 (d, J = 12.5 Hz, 1 H), 7.84–7.88 (m, 2 H).
and CuI (7.0 mg, 0.04 mmol) were dissolved in degassed THF or
MeCN (5 mL). Then Et N (0.14 mL, 1.00 mmol for alkyne 2c or
.17 mL, 1.25 mmol for all other alkynes 2) as well as acid chloride
(1 mmol) and alkyne 2 (1 mmol) were added successively to the
1
3
3
C NMR (CDCl , 75 MHz): = 11.6 (CH ), 14.7 (CH ), 42.7
3
3
3
0
1
(CH ), 50.4 (CH ), 91.6 (CH), 127.4 (CH), 128.3 (CH), 130.6 (CH),
2 2
1
40.7 (Cquat), 152.3 (CH), 188.6 (Cquat).
solution (for experimental details see Table 3). The reaction mix-
ture was stirred for 1–3 h until the conversion was complete (mon-
itored by TLC). Finally, Na CO ·10H O (973.0 mg, 3.40 mmol for
+
+
EI + Q1MS: m/z (%) = 203 (M , 46), 186 (M – OH, 30), 105 (Ph-
CO , 100).
+
2
3
2
alkyne 2c or 687.0 mg, 2.40 mmol for all other alkynes 2) and ami-
dinium chloride 6 (1.2 mmol or 2.50 mmol of guanidine hydrochlo-
ride 6g) were added to the suspension and the reaction mixture was
heated to reflux temperature for 12–14 h. After cooling to r.t., the
crude products were purified by chromatography on silica gel to
give the analytically pure pyrimidines 7 as oils (7a, 7d, 7h, 7i) or
crystalline solids (7b, 7c, 7e–g, 7j, 7k) (crystallization was done
from pentane–CH Cl or MeOH).
HRMS: m/z calcd for C H NO: 203.1306; found: 203.1314.
1
3
17
(
Z)-3-Butylamino-3-phenyl-1-thiophen-2-yl-propenone (5i)
According to the standard procedure, the reaction with amine 4d
0.11 mL, 1.1 mmol) gave 270 mg (95%) of 5i as yellow crystals;
(
mp 57–58 °C.
1
H NMR (CDCl , 300 MHz): = 0.84 (t, J = 7.4 Hz, 3 H), 1.30–
3
2
2
1
1
.43 (m, 2 H), 1.48–1.59 (m, 2 H), 3.19 (q, J = 6.6 Hz, 2 H), 5.62 (s,
H), 7.05 (dd, J = 5.1, 3.7 Hz, 1 H), 7.38–7.48 (m, 6 H), 7.53 (dd,
4
-Butyl-6-phenyl-2-thiophen-2-ylpyrimidine (7a)
J = 3.7, 1.1 Hz, 1 H), 11.08 (br s, 1 H).
Yellow oil.
IR (neat): 1575, 1530, 1438, 1376 cm–1.
1
3
C NMR (CDCl , 75 MHz): = 13.6 (CH ), 19.8 (CH ), 32.7
3
3
2
(
CH ), 44.5 (CH ), 92.8 (CH), 127.4 (CH), 127.6 (CH), 127.6 (CH),
2 2
1
H NMR (CDCl , 250 MHz): = 0.84 (t, J = 7.2 Hz, 3 H), 1.26–1.38
1
1
28.5 (CH), 129.4 (CH), 129.8 (CH), 135.4 (Cquat), 147.1 (Cquat),
66.4 (Cquat), 181.0 (Cquat).
3
(m, 2 H), 1.64–1.75 (m, 2 H), 2.71 (t, J = 7.6 Hz, 2 H), 7.04 (dd,
J = 3.7, 5.1 Hz, 1 H), 7.24 (s, 1 H), 7.36–7.40 (m, 4 H), 8.02–8.07
+
+
EI MS (70 eV): m/z (%) = 285 (M , 100), 268 (M – OH, 49), 111
(
m, 3 H).
+
(
2-ThCO , 63).
1
3
C NMR (CDCl , 75 MHz): = 13.9 (CH ), 22.4 (CH ), 30.8
3
3
2
Anal. Calcd for C H NOS (285.4): C, 71.54; H, 6.71; N, 4.91.
1
7
19
(
(
(
CH ), 37.6 (CH ), 112.8 (CH), 127.1 (CH), 128.0 (CH), 128.7
CH), 128.7 (CH), 129.4 (CH), 130.6 (CH), 137.0 (Cquat), 144.1
Cquat), 161.1 (Cquat), 163.6 (Cquat), 171.6 (Cquat).
2 2
Found: C, 71.44; H, 6.68; N, 4.99.
(
Z)-3-Benzylamino-3-phenyl-1-thiophen-2-ylpropenone (5j)
According to the standard procedure, the reaction with amine 4e
0.13 mL, 1.2 mmol) gave 310 mg (97%) of 5j as yellow crystals;
+
+
+
MS-FAB : m/z (%) = 295 [(M + H) , 100], 265 [(M + H) – H S, 8],
2
+
2
52 [(M + H) – C H , 28].
(
3
7
mp 110–111 °C.
UV/Vis (CH Cl ):
( ) = 260 (19500), 294 nm (19100).
2
2
max
1
H NMR (CDCl , 300 MHz): = 4.38 (d, J = 6.3 Hz, 2 H), 5.72 (s,
3
HRMS: m/z calcd for C H N S + H: 295.1261; found: 295.1250.
18 18 2
1
H), 7.07 (dd, J = 5.1, J = 3.7 Hz, 1 H), 7.19–7.50 (m, 11 H), 7.58
(
1
dd, J = 3.7, 1.1 Hz, 1 H), 11.36 (br s, 1 H).
4
-Phenyl-6-pyridin-2-yl-2-thiophen-2-ylpyrimidine (7b)
3
Yellow crystals; mp 174 °C.
C NMR (CDCl , 75 MHz): = 48.5 (CH ), 93.7 (CH), 126.9
3
2
(
(
(
CH), 127.4 (CH), 127.7 (CH), 127.8 (CH), 127.82 (CH), 128.6
CH), 128.7 (CH), 129.6 (CH), 130.2 (CH), 135.3 (Cquat), 138.3
Cquat), 147.1 (Cquat), 166.4 (Cquat), 181.7 (Cquat).
IR (KBr): 1577, 1568, 1532, 1365, 765 cm–1.
1
H NMR (CDCl , 250 MHz): = 7.12 (dd, J = 3.7, 5.0 Hz, 1 H),
3
7
7
8
.18 (s, 1 H), 7.35 (dt, J = 1.2, 7.4 Hz, 1 H), 7.48–7.52 (m, 3 H),
.83 (dt, J = 1.9, 7.8 Hz, 1 H), 8.14 (dd, J = 1.2, 3.7 Hz, 1 H), 8.28–
.32 (m, 2 H), 8.57–8.62 (m, 2 H), 8.66–8.70 (m, 1 H).
+
+
EI MS (70 eV): m/z (%) = 319 (M , 100), 302 (M – OH, 23).
Anal. Calcd for C H NOS (319.43): C, 75.20; H, 5.36; N, 4.38; S,
1
2
0
17
0.04. Found: C, 75.12; H, 5.50; N, 4.58; S, 9.75.
13
C NMR (CDCl , 75 MHz): = 109.9 (CH), 121.7 (CH), 125.1
3
(
(
(
CH), 127.2 (CH), 128.0 (CH), 128.6 (CH), 128.7 (CH), 129.4
CH), 130.7 (CH), 136.7 (Cquat),136.8 (CH), 143.9 (Cquat), 149.2
CH), 154.1 (Cquat), 161.1 (Cquat), 163.4 (Cquat), 165.0 (Cquat).
(
Z)-3-[2-(1H-Indol-3-yl)ethylamino]-3-phenyl-1-thiophen-2-yl-
propenone (5k)
According to the standard procedure, the reaction with amine 4f
+
+
MS-FAB : m/z (%) = 316 [(M + H) , 100].
(320 mg, 2 mmol) gave 290 mg (78%) of 5k as yellow crystals; mp
1
33–134 °C.
UV/Vis (CH Cl ): ( ) = 242 (26800), 252 (31500), 272
2
2
max
1
(36200), 282 (37300), 290 (35000), 302 (28000), 338 nm (9300).
H NMR (CDCl , 300 MHz): = 2.98 (t, J = 7.0 Hz, 2 H), 3.51 (q,
3
J = 6.8 Hz, 2 H), 5.61 (s, 1 H), 7.00–7.49 (m, 12 H), 7.55 (dd,
J = 3.7, 1.1 Hz, 1 H), 8.32 (s, 1 H), 11.00 (br s, 1 H).
2
-(4-Methoxyphenyl)-4-phenyl-6-thiophen-2-ylpyrimidine (7c)
Colorless crystals; mp 136 °C.
IR (KBr): 1569, 1528, 1513, 1367, 1251 cm–1.
1
3
C NMR (CDCl , 75 MHz): = 26.8 (CH ), 45.1 (CH ), 93.0 (CH),
3
2
2
1
1
1
1
11.1 (CH), 119.8 (Cquat), 118.1 (CH), 119.1 (CH), 121.7 (CH),
22.5 (CH), 126.9 (Cquat), 127.4 (CH), 127.4 (CH), 127.5 (CH),
28.3 (CH), 129.2 (CH), 129.7 (CH), 135.2 (Cquat), 136.2 (Cquat),
47.0 (Cquat), 166.5 (Cquat), 181.1 (Cquat).
1
H NMR (CDCl , 250 MHz): = 3.82 (s, 3 H), 6.96 (d, J = 8.9 Hz,
3
2 H), 7.12 (dd, J = 5.1 Hz, J = 3.8 Hz, 1 H), 7.45–7.47 (m, 4 H),
7.71 (s, 1 H), 7.83 (dd, J = 3.8 Hz, J = 1.1 Hz, 1 H), 8.15–8.17 (m,
2 H), 8.55 (d, J = 8.9 Hz, 2 H).
+
+
EI MS (70 eV): m/z (%) = 372 (M , 17), 242 (M – C H N, 100).
9
8
1
3
C NMR (CDCl , 75 MHz): = 55.7 (CH ), 107.9 (CH), 113.8
3
3
Anal. Calcd for C H N OS (372.49): C, 74.16; H, 5.41; N, 7.52.
23
20
2
(
(
CH), 127.1 (CH), 127.3 (CH), 128.3 (CH), 128.9 (CH), 129.8
CH), 130.2 (CH), 130.3 (Cquat), 130.8 (CH), 137.8 (Cquat), 143.4
Found: C, 73.58; H, 5.32; N, 7.68.
HRMS: m/z calcd for C H N OS: 372.1292; found: 372.1331.
2
3
20
2
(Cquat), 159.6 (Cquat), 162.0 (Cquat), 164.1 (Cquat), 164.4 (Cquat).
+
+
MS-FAB : m/z (%) = 345 [(M + H) , 100].
Synthesis 2003, No. 18, 2815–2826 © Thieme Stuttgart · New York