Efficient [5 + 1]-strategy for the assembly of 1,8-naphthyridin-4(1H)-ones by domino amination/conjugate addition reactions of 1-(2-chloropyridin-3-yl) prop-2-yn-1-ones with amines

Article abstract of DOI:10.1039/c2ob07030h

A facile synthetic approach for the synthesis of 1,8-naphthyridine-4(1H)- one derivatives via a catalyst free and Pd-supported tandem amination sequence is developed and described. In a case of aliphatic amines reaction proceeds in a catalyst free mode, however anilines demand Pd-supported reaction conditions. The Royal Society of Chemistry 2012.

Full text of DOI:10.1039/c2ob07030h

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Supporting Information
Efficient [5+1]-Strategy for the Assembly of 1,8-Naphthyridines by Domino
Amination/Conjugate Addition Reactions of 1-(2-Chloropyridin-3-yl)prop-2-yn-1-ones
with Amines
1
a,b
a
a
a
a
Viktor O. Iaroshenko, * Ingo Knepper, Muhammad Zahid, Sergii Dudkin, Rene Kuzora,
a
a,c
Alexander Villinger, Peter Langer *
a
Institut für Chemie, Universität Rostock,, Albert-Einstein-Str. 3a, 18059 Rostock, Germany. Fax: 00 49 381 49864112; Tel: 0049 381
4
986410; E-mail: viktor.iaroshenko@uni-rostock.de, iva108@googlemail.com.
b
c
National Taras Shevchenko University, 62 Volodymyrska st., Kyiv-33, 01033, Ukraine.E-mail: iva108@googlemail.com.
Leibniz-Institut für Katalyse e. V. an der Universität Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany.
Table of Contents
(
(
(
(
(
A) Experimental Section
B) Spectral data
2-3
4-29
30-35
36-140
141-145
C) UV- and Fluorescence-Study
1
13
D) Copies of MS, H and C NMR spectra
E) X-Ray structures

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(A)
Experimental Section
The dry solvents DMF and THF were purchased directly from ACROS as AcroSeal bottles. Other solvents were purified by destination. All
1
13
reactions were carried out under an inert atmosphere. For H and C NMR spectra the deuterated solvents indicated were used. Mass
spectrometric data (MS) were obtained by electron ionization (EI, 70 eV), chemical ionization (CI, isobutane) or electrospray ionization (ESI).
For preparative scale chromatography silica gel 60 (0.063-0.200 mm, 70–230 mesh) was used. The absorption spectra were measured on a
2
–
5
Perkin Elmer UV/VIS Spectrometer Lambda 2 in dichloromethane (c = 2.5 * 10 mol/l). The fluorescence spectra were recorded on a Hitachi F-
–
4
4
010 fluorescence spectrometer in dichloromethane (c = 10 mol/l; excitation wavelength: 350 nm). The solvent was distilled before use.
1
9
Compound 1 was obtained starting from commercially available 2-chloropyridine-3-carboxylic acid by the method described previously.
Acetylenes 2 and amines 4 are commercially available compounds.
Procedure A – General procedure 1-(2-chloropyridin-3-yl)prop-2-yn-1-ones (3): 1 g (6.35 mmol) of 2-chloronicotinic acid was refluxed in
an excess of SOCl . After 3 h the SOCl was removed in vacuo and the crude white residue used without further purification.
2
2
1
.05 Equiv of the corresponding acetylene, 0.02 equiv (2 mol%) of PdCl (PPh ) , 0.04 equiv (4 mol%) of CuI and 1.0 equiv of the chlorinated 2-
2 3 2
chloropyridine-3-carboxylic acid chloride (1) are added to dry THF under argon atmosphere in a pressure tube. The mixture is cooled to 0 °C,
.05 equiv NEt are added and the mixture is stirred at room temperature. After 3 h the reaction mixture is washed with water and extracted with
1
3
ethylacetate. The combined phases are dried over Na SO , the solvent is removed in vacuo and the residue purified by column chromatography
2
4
(eluent : n-heptane/ethylacetate).
Procedure B – General procedure for alkylamines (5b-k, 5q-t, 5v, 5w): 2.0 equiv of the corresponding alkylamine, 2.0 equiv of K CO and
2
3
1
.0 equiv of the corresponding 1-(2-chloropyridin-3-yl)prop-2-yn-1-one are heated at 150 °C (100 °C if a TMS group is present in the molecule)
in dry DMF under argon atmosphere in a pressure tube. After 16 h the solvent is removed in vacuo and the crude product is purified by column
chromatography (eluent: n-heptane/ethylacetate).

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Procedure C – General procedure for anilines (5a, 5l-p, 5u): 2.0 equiv of the corresponding aniline, 2.0 equiv of K CO , 0.1 equiv (10 mol%)
2
3
of Pd(PPh ) and 1.0 equiv of the corresponding 1-(2-chloropyridin-3-yl)prop-2-yn-1-one are heated at 150 °C in dry DMF under argon
3
4
atmosphere in a pressure tube. After 16 h the solvent is removed in vacuo and the crude product is purified by column chromatography (eluent:
n-heptane/ethylacetate).
3
Procedure D – General procedure for bromination (20): 1.0 equiv of the starting material, 1.5 equiv of bromine and 6.0 equiv of Na CO in
2
3
THF are stirred at room temperature for 6 h. The solvent is removed in vacuo and the crude product purified by column chromatography (eluent:
n-heptane/ethylacetate).
Procedure E – General procedure for Suzuki-Coupling (21a-c): 1.0 equiv of the starting material, 1.1 equiv of the boronic acid, 0.05 equiv (5
mol%) Pd(PPh ) and 2.0 equiv K CO are heated in DMF for 16 h at 120 °C. The solvent is removed in vacuo and the crude product is purified
3
4
2
3
by column chromatography (eluent: n-heptane/ethylacetate).

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(B)
Spectral data
[1]
1
-(2-chloropyridin-3-yl)-3-phenylprop-2-yn-1-one (3a).
4
Starting with 2-chloropyridine-3-carboxylic acid chloride (1) (0.200 g, 1.14 mmol), PdCl (PPh ) (0.016 g, 0.023 mmol), CuI (0.009 g, 0.046
2
3 2
mmol), NEt (0.17 mL, 1.2 mmol) and phenylacetylene (0.13 mL, 1.2 mmol) in THF (10 mL), product 3a was isolated as a white solid (0.220 g,
3
[1]
1
8
0 %); mp 68-70 °C (lit. 69-71 °C); Procedure E. H NMR (CDCl , 250 MHz):  = 7.33-7.47 (m, 4H, H ), 7.57-7.61 (m, 2H, H ), 8.27 (dd,
3
Ar
Ar
4
3
4
3
13
J = 2.0 Hz, J = 7.7 Hz, 1H, H ), 8.50 (dd, J = 2.0 Hz, J = 4.8 Hz, 1H, H ). C NMR (CDCl , 63 MHz):   87.9, 95.7, 119.6, 122.4, 128.8,
Ar
Ar
3
1
31.4, 132.6, 133.2, 140.7, 149.5, 152.3, 175.5.
[2]
3
-(4-tert-butylphenyl)-1-(2-chloropyridin-3-yl)prop-2-yn-1-one (3b).
Starting with 2-chloropyridine-3-carboxylic acid chloride (1) (0.200 g, 1.14 mmol), PdCl (PPh ) (0.016 g, 0.023 mmol), CuI (0.009 g, 0.046
2
3 2
mmol), NEt (0.17 mL, 1.2 mmol) and 4-tert-butylphenylacetylene (0.22 mL, 1.2 mmol) in THF (10 mL), product 3b was isolated as a white-
3
1
brown solid (0.204 g, 60 %); mp 54-56 °C; Procedure E. H NMR (CDCl , 250 MHz):  = 1.26 (s, 9H, C(CH ) ), 7.32-7.39 (m, 3H, H ), 7.51-
3
3 3
Ar

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4
3
4
3
13
7
.55 (m, 2H, H ), 8.26 (dd, J = 2.0 Hz, J = 7.2 Hz, 1H, H ), 8.70 (dd, J = 2.0 Hz, J = 4.8 Hz, 1H, H ). C NMR (CDCl , 63 MHz):
Ar
Ar
Ar
3
–
1
~

= 31.0, 35.2, 87.9, 96.5, 116.5, 122.4, 125.9, 132.8, 133.2, 140.6, 149.5, 152.5, 155.3, 175.5. IR (ATR, cm ):

= 3038 (w), 2963 (w), 2904
(w), 2866 (w), 2351 (w), 2292 (w), 2190 (s), 1938 (w), 1644 (s), 1600 (m), 1573 (m), 1556 (m), 1504 (w), 1463 (w), 1439 (w), 1400 (s), 1364
+
(
w), 1291 (m), 1268 (w), 1258 (w), 1204 (m), 1185 (w), 1127 (w), 1113 (w), 1095 (m), 1062 (w), 1015 (w). m/z (%) = 297 (M-H , 25), 282
(
100), 254 (6), 226 (7), 185 (4), 155 (7), 140 (7), 112 (4), 95 (5), 76 (3), 41 (3). Anal. calcd for C H ClNO (297.78): C, 72.60 ; H, 5.42; N,
18
16
5
4
.70. Found: C, 72.36 ; H, 5.53; N, 4.86.
1
-(2-chloropyridin-3-yl)hex-2-yn-1-one (3c).
Starting with 2-chloropyridine-3-carboxylic acid chloride (1) (0.200 g, 1.14 mmol), PdCl (PPh ) (0.016 g, 0.023 mmol), CuI (0.009 g, 0.046
2
3 2
mmol), NEt (0.17 mL, 1.2 mmol) and 1-pentyne (0.12 mL, 1.2 mmol) in THF (10 mL), product 3c was isolated as a brown oil (0.140 g, 59 %);
3
1
3
3
Procedure E. H NMR (CDCl , 250 MHz):  = 0.99 (t, J = 7.4 Hz, 3H, CH ), 1.58-1.68 (m, 2H, CH ), 2.40 (t, J = 7.1 Hz, 2H, CH ), 7.31 (dd,
3
3
2
2
3
3
3
4
3
4
13
J = 4.8 Hz, J = 7.7 Hz, 1H), 8.20 (dd, J = 7.7 Hz, J = 2.0 Hz, 1H, H ), 8.46 (dd, J = 4.8 Hz , J = 2.0 Hz, 1H, H ). C NMR (CDCl ,
Ar
Ar
3
–
1
~
6
3 MHz):   13.6, 21.1, 21.3, 80.8, 99.5, 122.2, 132.6, 140.7, 149.3, 152.1, 175.6. IR (ATR, cm ):  = 3046 (w), 2965 (w), 2934 (w), 2905
(w), 2874 (w), 2278 (w), 2217 (m), 2201 (m), 1656 (s), 1572 (m), 1558 (m), 1462 (w), 1443 (w), 1421 (w), 1397 (s), 1338 (w), 1325 (w), 1287
+
(
m), 1266 (m), 1234 (m), 1138 (m), 1128 (m), 1069 (m), 1024 (m). m/z (%) = 207 (M , 18), 192 (3), 179 (34), 164 (5), 140 (16), 112 (14), 95
3
5
+
37
+
(
100), 76 (12), 66 (12), 53 (13), 39 (9). HRMS (ESI): calcd for C H ClNO ([M+H] ) 208.0524, found 208.0521, C H ClNO ([M+H] )
11 11 11 11
2
09.0421, found 209.0423.

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[2]
1
-(2-chloropyridin-3-yl)prop-2-yn-1-one (3d).
6
1
-(2-chloropyridin-3-yl)-3-(trimethylsilyl)prop-2-yn-1-one (3e) (0.800 g, 3.36 mmol), KF (1.900 g, 33.6 mmol) and dibenzo-18-crown-6 (0.030
mg, 0.083 mmol) are stirred at room temperature in THF (30 mL). After 2 h the solvent is removed in vacuo and the crude product is purified by
column chromatography (eluent: n-heptane/ethylacetate). The reaction afforded product 3d as a white solid (0.100 g, 18 %, product is unstable);
1
3
3
4
mp 98-100 °C. H NMR (CDCl , 300 MHz):  = 3.52 (s, 1H, C≡CH), 7.35 (dd, J = 4.8 Hz, J = 2.0 Hz, 1H, H ), 8.30 (dd, J = 2.0 Hz,
3
Ar
3
4
3
13
J = 7.8 Hz, 1H, H ), 8.49 (dd, J = 2.0 Hz, J = 4.8 Hz, 1H, H ). C NMR (CDCl , 63 MHz):   80.7, 82.9, 122.3, 131.3, 141.4, 149.7,
Ar
Ar
3
–1
~
1
52.7, 174.7. IR (ATR, cm ):

= 3059 (w), 3066 (w), 2922 (w), 2852 (w), 2077 (m), 1683 (w), 1656 (s), 1570 (m), 1556 (s), 1443 (w), 1403
+
(
s), 1265 (m), 1221 (m), 1133 (w), 1108 (s), 1064 (m). m/z (%) = 165 (M , 100), 137 (97), 130 (10), 113 (13), 102 (61), 85 (11), 76 (31), 62 (6),
35
+
37
+
5
1
3 (64), 50 (27). HRMS (ESI): calcd for C H ClNO ([M+H] ) 166.00542, found 166.00502, C H ClNO ([M+H] ) 168.00262, found
8 5 8 5
68.00247.
1
-(2-chloropyridin-3-yl)-3-(trimethylsilyl)prop-2-yn-1-one (3e).
Starting with 2-chloropyridine-3-carboxylic acid chloride (1) (0.200 g, 1.14 mmol), PdCl (PPh ) (0.016 g, 0.023 mmol), CuI (0.009 g, 0.046
2
3 2
mmol), NEt (0.17 mL, 1.2 mmol) and ethynyltrimethylsilane (0.17 mL, 1.2 mmol) in THF (10 mL), product 3e was isolated as a brown solid
3
1
3
3
(
0.163 g, 60 %); mp 32-34 °C; Procedure E. H NMR (CDCl , 300 MHz):  = 0.20 (s, 9H, Si(CH ) ), 7.10 (dd, 1H, J = 4.8 Hz, J = 7.6 Hz, 1H,
3
3 3

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4
3
4
3
13
H ), 7.70 (dd, 1H, J = 2.0 Hz, J = 7.6 Hz, 1H, H ), 8.22 (dd, 1H, J = 2.0 Hz, J = 4.8 Hz, 1H, H ). C NMR (CDCl , 63 MHz):
Ar
Ar
Ar
3
–1
~


  102.1, 104.5, 123.3, 132.9, 142.0, 150.5, 153.3, 176.0. IR (ATR, cm ): = 3046 (w), 2964 (w), 2901 (w), 2152 (w), 1658 (m), 1572
(w), 1555 (w), 1401 (m), 1279 (w), 1268 (w), 1248 (m), 1232 (w), 1221 (w), 1128 (w), 1109 (m), 1098 (w), 1061 (w), 1005 (m). m/z (%) = 236
+
(
M-H , 13), 222 (100), 194 (21), 194 (21), 179 (7), 158 (20), 143 (39), 130 (27), 117 (10), 93 (12), 76 (11), 63 (10), 53 (6), 43 (7). Anal. calcd
for C H NOClSi (237.76): C, 55.57; H, 5.09; N, 5.89. Found: C, 55.35; H, 4.86; N, 6.29.
1
1
12
7
1
,2-diphenyl-1,8-naphthyridin-4(1H)-one (5a).
Starting with 1-(2-chloropyridin-3-yl)-3-phenylprop-2-yn-1-one (3a) (0.150 g, 0.62 mmol), Pd(PPh ) (0.072 g, 0.062 mmol), K CO (0.171 g,
3
4
2
3
1
.24 mmol) and aniline (0.11 mL, 1.24 mmol) in DMF (10 mL) product 5a was isolated as a brown solid (0.083 g, 45 %); mp 290-292 °C;
1
4
3
Procedure B; H NMR (CDCl , 250 MHz):  = 6.43 (s, 1H, C=CH), 7.06-7.31 (m, 11H, H ), 8.56 (dd, J = 2.1 Hz, J = 4.5 Hz, 1H, H ), 8.72
3
Ar
Ar
4
3
13
(
dd, J = 2.0 Hz, J = 8.1 Hz, 1H, H ). C NMR (CDCl , 63 MHz):   113.5, 120.0, 120.8, 127.9, 128.3, 128.8, 128.8, 129.0, 130.1, 135.5,
Ar
3
–
1
~
1
35.6, 138.8, 151.9, 152.5, 155.1, 178.2. IR (ATR, cm ):

= 3055 (w), 2953 (w), 2922 (w), 2852 (w), 1631 (m), 1595 (w), 1491 (w), 1481
+
(
w), 1437 (w), 1412 (m), 1336 (w), 1309 (w), 1275 (w), 1191 (w), 1118 (w), 1070 (w), 1036 (w). m/z (%) = 297 (M-H , 100), 269 (9), 195 (5),
+
1
67 (4), 140 (3), 77 (5), 51 (3). HRMS (ESI): calcd for C H N O ([M+H] ) 299.1179, found 299.1180.
2
0
14
2
1
-benzyl-2-phenyl-1,8-naphthyridin-4(1H)-one (5b).

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8
Starting with 1-(2-chloropyridin-3-yl)-3-phenylprop-2-yn-1-one (3a) (0.150 g, 0.62 mmol), K CO (0.171 g, 1.24 mmol) and benzylamine (0.14
2
3
1
mL, 1.24 mmol) in DMF (10 mL), product 5b was isolated as a white solid (0.190 g, 98 %); mp 134-136 °C; Procedure A. H NMR (CDCl ,
3
2
50 MHz):  = 5.57 (s, 2H, CH ), 6.27 (s, 1H, C=CH), 6.70-6.73 (m, 2H, H ), 7.08-7.19 (m, 5H, H ), 7.26-7.36 (m, 4H, H ), 8.64 (dd,
2
Ar
Ar
Ar
4
3
4
3
13
J = 2.0 Hz, J = 4.4 Hz, 1H, H ), 8.71 (dd, J = 2.0 Hz, J = 8.0 Hz, 1H, H ). C NMR (CDCl , 63 MHz):   49.5, 114.0, 120.0, 121.4,
Ar
Ar
3
–
1
~
1
1
1
26.3, 127.2, 128.4, 128.4, 128.5, 129.6, 135.2, 135.9, 137.6, 150.9, 152.4, 155.8, 177.8. IR (ATR, cm ):  = 3049 (w), 3025 (w), 2958 (w),
633 (m), 1615 (w), 1591 (m), 1575 (m), 1484 (m), 1453 (w), 1440 (w), 1426 (m), 1411 (m), 1361 (w), 1335 (w), 1327 (w), 1315 (w), 1291 (w),
+
254 (w), 1235 (w), 1225 (w), 1185 (w), 1139 (w), 1077 (w), 1057 (w), 1043 (w), 1034 (w), 1027 (w). m/z (%) = 311 (M-H , 100), 283 (4), 233
(
10), 181 (3), 91 (54), 65 (7). Anal. calcd for C H N O (312.37): C, 80.75 ; H, 5.16; N, 8.97. Found: C, 80.38; H, 5.05; N, 8.98.
21 17 2
1
-(2-chlorobenzyl)-2-phenyl-1,8-naphthyridin-4(1H)-one (5c).
Starting with 1-(2-chloropyridin-3-yl)-3-phenylprop-2-yn-1-one (3a) (0.150 g, 0.62 mmol), K CO (0.171 g, 1.24 mmol) and
2
3
2
-chlorobenzylamine (0.15 mL, 1.24 mmol) in DMF (10 mL), product 5c was isolated as a white solid (0.181 g, 84 %); mp 175-178 °C;

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1
Procedure A. H NMR (CDCl , 300 MHz):  = 5.57 (s, 2H, CH ), 6.32 (s, 1H, C=CH), 6.52-6.56 (m, 1H, H ), 6.99-7.13 (m, 4H, H ), 7.22-
3
2
Ar
Ar
4
3
4
3
13
7
.39 (m, 5H, H ), 8.61 (dd, J = 2.0 Hz, J = 4.5 Hz, 1H, H ), 8.73 (dd, J = 2.0 Hz, J = 8.0 Hz, 1H, H ). C NMR (CDCl , 63 MHz):
Ar Ar Ar 3
–
1

= 47.8, 114.0, 120.2, 126.8, 126.9, 127.9, 128.2, 128.6, 129.4, 129.7, 131.9, 134.7, 135.2, 135.9, 150.8, 152.7, 155.8, 177.7.IR (ATR, cm ):
~

= 3050 (w), 3036 (w), 3025 (w), 2953 (w), 2920 (w), 2850 (w), 1632 (s), 1615 (w), 1591 (m), 1575 (w), 1548 (w), 1483 (m), 1472 (w), 1441
(w), 1441 (w), 1423 (m), 1409 (s), 1339 (w), 1314 (w), 1294 (w), 1255 (w), 1235 (w), 1224 (w), 1138 (w), 1127 (w), 1038 (m). m/z (%) = 345
+
9
(
M-H , 23), 311 (100), 233 (9), 155 (6), 125 (34), 89 (7), 77 (3). Anal. calcd for C H ClN O (346.81): C, 72.73; H, 4.36; N, 8.08. Found: C,
2
1
15
2
7
2.61 ; H, 4.40 ; N, 8.02.
1
-cyclopentyl-2-phenyl-1,8-naphthyridin-4(1H)-one (5d).
Starting with 1-(2-chloropyridin-3-yl)-3-phenylprop-2-yn-1-one (3a) (0.150 g, 0.62 mmol), K CO (0.171 g, 1.24 mmol) and
2
3
cyclopentylamine (0.12 mL, 1.24 mmol) in DMF (10 mL), product 5d was isolated as a white solid (0.173 g, 96 %); mp 223-224 °C; Procedure
1
A. H NMR (CDCl , 250 MHz):  = 1.40-1.48 (m, 2H, CH ), 1.65-1.75 (m, 2H, CH ), 2.00-2.09 (m, 2H, CH ), 2.41-2.53 (m, 2H, CH ), 4.49-
3
2
2
2
2
1
3
4
.58 (m, 1H, CH), 6.17 (s, 1H, C=CH), 7.24-7.28 (m, 1H, H ), 7.36-7.45 (m, 5H, H ), 8.64-8.68 (m, 2H, H ). C NMR (CDCl , 63 MHz):
Ar
Ar
Ar
3
–
1
~

  25.9, 30.6, 63.1, 113.6, 119.4, 122.5, 127.7, 128.8, 129.4, 135.8, 136.8, 150.7, 150.7, 156.6, 177.6. IR (ATR, cm ):

= 3055 (w), 3035
(w), 3001 (w), 2951 (w), 2867 (w), 1633 (s), 1614 (m), 1605 (m), 1591 (s), 1553 (w) 1532 (w), 1484 (s), 1454 (m), 1442 (m), 1429 (m), 1393
+
(
m), 1325 (m), 1301 (m), 1247 (m), 1233 (m), 1191 (m), 1168 (w), 1157 (w), 1138 (m), 1040 (m), 1035 (m). m/z (%) = 290 (M , 11), 261 (2),

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2
9
47 (2), 222 (100), 194 (44), 166 (4), 145 (2), 117 (2), 91 (3), 78 (2), 67 (2), 41 (3). Anal. calcd for C H N O (290.36): C, 78.59; H, 6.25; N,
19 18 2
.65. Found: C, 78.49 ; H, 6.26 ; N, 9.69.
1
-cyclohexyl-2-phenyl-1,8-naphthyridin-4(1H)-one (5e).
1
0
Starting with 1-(2-chloropyridin-3-yl)-3-phenylprop-2-yn-1-one (3a) (0.150 g, 0.62 mmol), K CO (0.171 g, 1.24 mmol) and
2
3
cyclohexylamine (0.14 mL, 1.24 mmol) in DMF (10 mL), product 5e was isolated as a white solid (0.185 g, 98 %); mp 262-263 °C; Procedure
1
A. H NMR (CDCl , 250 MHz):  = 0.81-0.98 (m, 2H, HCyclohexyl), 1.11-1.27 (m, 1H, HCyclohexyl), 1.46-1.51 (m, 1H, HCyclohexyl), 1.63-1.72 (m, 4H,
3
1
3
HCyclohexyl), 2.83-2.98 (m, 2H, HCyclohexyl), 3.94-4.04 (m, 1H, HCyclohexyl), 6.18 (s, 1H, C=CH), 7.24-7.46 (m, 6H, H ), 8.64-8.68 (m, 2H, H ). C
Ar
Ar
NMR (CDCl , 63 MHz):  = 25.1, 26.5, 30.7, 63.9, 113.7, 119.5, 122.2, 127.6, 128.7, 129.4, 135.5, 136.8, 150.8, 151.5, 156.4, 177.6. IR
3
–
1
~
(
ATR, cm ):  = 3053 (w), 3035 (w), 2981 (w), 2947 (w), 2916 (w), 2847 (w), 1635 (m), 1604 (w), 1591 (m), 1574 (w), 1483 (m), 1455 (w),
1
1
444 (w), 1427 (w), 1421 (w), 1393 (m), 1340 (w), 1393 (m), 1340 (w), 1320 (w), 1303 (w), 1252 (m), 1238 (w), 1227 (w), 1189 (w), 1121 (w),
+
060 (w), 1044 (w), 1060 (w), 1044 (w). m/z (%) = 304 (M-H , 7), 222 (100), 194 (28), 166 (3), 145 (3), 117 (3), 91 (3), 67 (3), 55 (3), 41 (4).
Anal. calcd for C H N O (304.39): C, 78.92; H, 6.62; N, 9.20. Found: C, 78.85; H, 6.63; N, 9.08.
2
0
20
2
1
-phenethyl-2-phenyl-1,8-naphthyridin-4(1H)-one (5f).

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
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1
1
Starting with 1-(2-chloropyridin-3-yl)-3-phenylprop-2-yn-1-one (3a) (0.150 g, 0.62 mmol), K CO (0.171 g, 1.24 mmol) and
2
3
2
-phenylethylamine (0.16 mL, 1.24 mmol) in DMF (10 mL), product 5f was isolated as a white solid (0.186 g, 92 %); mp 163-165 °C;
1
3
3
Procedure A. H NMR (CDCl , 250 MHz):  = 2.84 (t, 2H, J = 7.7 Hz, CH ), 4.47 (t, 2H, J = 7.7 Hz, CH ), 6.21 (s, 1H, C=CH), 6.73-6.76 (m,
3
2
2
1
3
2
1
H, H ), 7.09-7.2 (m, 5H, H ), 7.31-7.44 (m, 4H, H ), 8.69-8.77 (m, 2H, H ). C NMR (CDCl , 63 MHz):   35.5, 48.1, 113.4, 119.8,
Ar
Ar
Ar
Ar
3
–
1
~
21.6, 126.6, 128.2, 128.5, 128.6, 128.8, 129.5, 135.4, 135.9, 137.9, 150.5, 152.3, 155.4, 177.6. IR(ATR, cm ):

= 3062 (w), 3045 (w), 3023
(w), 2994 (w), 2958 (w), 1621 (m), 1589 (m), 1553 (m), 1486 (m), 1453 (m), 1442 (m), 1433 (m), 1414 (m), 1368 (m), 1333 (m), 1314 (m),
1
230 (m), 1256 (m), 1244 (m), 1230 (m), 1198 (m), 1174 (w), 1154 (w), 1144 (m), 1135 (m), 1041 (m), 1027 (m), 1000 (m). m/z (%) = 326
+
(
M , 7), 235 (91), 222 (100), 194 (14), 166 (2), 133 (6), 106 (11), 91 (4), 78 (12), 65 (2), 51 (4). Anal. calcd for C H N O (326.39): C, 80.53;
2
2
18
2
H, 5.85; N, 8.42. Found: C, 80.96; H, 5.56 ; N, 8.58.
1
-(2-hydroxyethyl)-2-phenyl-1,8-naphthyridin-4(1H)-one (5g).

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Starting with 1-(2-chloropyridin-3-yl)-3-phenylprop-2-yn-1-one (3a) (0.150 g, 0.62 mmol), K CO (0.171 g, 1.24 mmol) and
2
3
ethanolamine (0.075 mL, 1.24 mmol) in DMF (10 mL), product 5g was isolated as a white solid (0.101 g, 61 %); mp 174-175 °C; Procedure A.
1
3
3
H NMR (CDCl , 300 MHz):  = 3.82 (t, J = 5.1 Hz, 2H, CH ), 4.39 (t, J = 5.1 Hz, 2H, CH ), 6.15 (s, 1H, C=CH), 7.25-7.29 (m, 1H, H ),
3
2
2
Ar
4
3
4
3
13
7
.35-7.44 (m, 5H, H ), 8.51 (dd, J = 2.0 Hz, J = 8.0 Hz, 1H, H ), 8.65 (dd, J = 2.0 Hz, J = 4.5 Hz, 1H, H ). C NMR (CDCl , 63 MHz): 
Ar
Ar
Ar
3
–
1
~
=
49.7, 61.5, 113.6, 119.8, 121.4, 128.6, 128.7, 129.5, 135.5, 136.0, 150.9, 151.9, 156.3, 177.2.IR (ATR, cm ):

= 3210 (w), 3071 (w), 2957
1
2
(w), 2921 (w), 2864 (w), 1610 (m), 1593 (s), 1562 (w), 1557 (w), 1538 (w), 1494 (w), 1486 (m), 1445 (w), 1428 (w), 1411 (m), 1323 (w), 1316
+
(
w), 1301 (w), 1258 (w), 1248 (w), 1234 (w), 1205 (w), 1143 (w), 1043 (s), 1013 (w). m/z (%) = 266 (M , 20), 247 (20), 235 (100), 222 (80),
2
05 (9), 194 (22), 166 (3), 133 (8), 106 (12), 78 (13), 51 (5). Anal. calcd for C H N O (266.29): C, 72.16; H, 5.30; N, 10.52. Found: C, 72.31;
16 14 2 2
H, 5.28; N, 10.28.
1
-heptyl-2-phenyl-1,8-naphthyridin-4(1H)-one (5h).
Starting with 1-(2-chloropyridin-3-yl)-3-phenylprop-2-yn-1-one (3a) (0.150 g, 0.62 mmol), K CO (0.171 g, 1.24 mmol) and
2
3
n-heptylamine (0.18 mL, 1.24 mmol) in DMF (10 mL), product 5h was isolated as a white solid (0.191 g, 96 %); mp 144-146 °C; Procedure A.
1
3
3
H NMR (CDCl , 250 MHz):  = 0.73-0.78 (t, J = 7.0 Hz, 3H, CH ), 1.02-1.14 (m, 8H, CH ), 1.51-1.56 (m, 2H, CH ), 4.23 (t, J = 8.0 Hz, 2H,
3
3
2
2
1
3
CH ), 6.22 (s, 1H, C=CH), 7.28-7.45 (m, 6H, H ), 8.67-8.71 (m, 2H, H ). C NMR (CDCl , 63 MHz):   14.0, 22.4, 26.4, 28.3, 29.7, 31.5,
2
Ar
Ar
3

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–
1
~
4
2
1

6.7, 113.5, 119.7, 121.6, 128.2, 129.0, 129.4, 135.6, 135.7, 150.5, 152.1, 155.4, 177.5. IR (ATR, cm ): = 3101 (w), 3057 (w), 2956 (w),
920 (w), 2852 (w), 2352 (w), 2163 (w), 2126 (w), 2071 (w), 1962 (w), 1930 (w), 1796 (w), 1756 (w), 1609 (s), 1589 (s), 1532 (m), 1494 (m),
474 (w), 1456 (m), 1443 (w), 1432 (w), 1415 (w), 1380 (m), 1340 (m), 1303 (w), 1233 (m), 1155 (w), 1130 (w), 1091 (w), 1048 (w), 1024 (w).
+
m/z (%) = 320 (27, M ), 277 (5), 263 (8), 249 (10), 235 (57), 222 (100), 207 (6), 194 (25), 166 (4), 133 (4), 106 (7), 78 (6), 41 (4). Anal. calcd
for C H N O (320.43): C, 78.71; H, 7.55; N, 8.74. Found: C, 78.87; H, 7.57; N, 8.53.
2
1
24
2
1
3
1
-allyl-2-phenyl-1,8-naphthyridin-4(1H)-one (5j).
Starting with 1-(2-chloropyridin-3-yl)-3-phenylprop-2-yn-1-one (3a) (0.150 g, 0.62 mmol), K CO (0.171 g, 1.24 mmol) and
2
3
allylamine (0.054 mL, 1.24 mmol) in DMF (10 mL), product 5j was isolated as a white-brown solid (0.120 g, 74 %); mp 79-81 °C; Procedure A.
1
3
2
H NMR (CDCl , 300 MHz): δ = 4.69 (dd, J = 17.0 Hz, J = 0.9 Hz, 1H, CH -CH=CHH), 4.86-4.88 (m, 2H, CH -CH=CHH), 5.00-5.04 (dd,
3
2
2
3
2
J = 10.3 Hz, J = 0.9 Hz, 1H, CH -CH=CHH), 5.75-5.87 (m, 1H, CH -CH=CHH), 6.25 (s, 1H, O=C-CH=C), 7.29-7.44 (m, 6H, H ), 8.68-8.70
2
2
Ar
1
3
(
m, 2H, H ). C NMR (CDCl , 63 MHz): δ = 48.6, 113.6, 116.9, 119.8, 128.3, 128.3, 128.4, 129.6, 133.2, 135.1, 135.8, 150.4, 152.2, 155.5,
Ar
3
–
1
~
1
1
1
77.6. IR (ATR, cm ):

= 3145 (w), 3053 (w), 2979 (w), 2950 (w), 1631 (s), 1614 (m), 1602 (m), 1590 (s), 1575 (m), 1548 (w), 1483 (s),
442 (w), 1424 (m), 1409 (s), 1360 (w), 1333 (w), 1312 (w), 1289 (w), 1254 (m), 1236 (m), 1224 (m), 1186 (w), 1159 (w), 1145 (w), 1074 (w),
+
041 (w), 1033 (w), 1001 (w). m/z (%) = 261 (M-H , 91), 247 (100), 233 (10), 194 (76), 166 (9), 139 (6), 97 (13), 76 (4). Anal. calcd for
C H N O (262.31): C, 77.84; H, 5.38; N, 10.68. Found: C, 77.75; H, 5.44; N, 10.98.
17
14
2

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2
-phenyl-1,8-naphthyridin-4(1H)-one (5k).
1
4
Starting with 1-(2-chloropyridin-3-yl)-3-phenylprop-2-yn-1-one (3a) (0.150 g, 0.62 mmol), K CO (0.171 g, 1.24 mmol) and
2
3
ammonia (7 N solution in methanol, 0.18 mL, 1.26 mmol) in DMF (10 mL), product 5k was isolated as a white-brown solid (0.098 g, 71 %); mp
1
4
3
2
3
24-226 °C °C; Procedure A. H NMR (CDCl , 300 MHz):  = 6.39 (s, 1H, C=CH), 7.42 (dd, J = 4.4 Hz, J = 8.0 Hz, 1H, H ), 7.52-7.58 (m,
3
Ar
4
3
4
3
H, H ), 7.82-7.86 (m, 2H, H ), 8.47 (dd, J = 1.9 Hz, J = 7.9 Hz, 1H, H ), 8.78 (dd, J = 1.9 Hz, J = 3.2 Hz, 1H, H ), 12.34 (br, 1H, NH).
Ar
Ar
Ar
Ar
1
3
C NMR (CDCl , 63 MHz):   108.5 (CH), 119.3 (C), 119.9 (CH), 127.7 (CH), 128.8 (CH), 130.6 (CH), 133.6 (C), 134.5 (CH), 151.3 (C),
3
–
1
~
1
1
1

51.5 (C), 153.1 (CH), 177.2 (C=O). IR (ATR, cm ): = 3218 (w), 3130 (w), 3076 (w), 3052 (w), 2919 (w), 2867 (w), 2810 (w), 2748 (w),
643 (w), 1627 (w), 1592 (m), 1580 (m), 1549 (m), 1504 (m), 1495 (m), 1442 (w), 1424 (m), 1403 (w), 1393 (w), 1335 (w), 1314 (m), 1258 (w),
+
234 (w), 1223 (w), 1190 (w), 1144 (w), 1119 (w), 1090 (w), 1039 (w), 1028 (w), 1000 (w). m/z (%) = 222 (M , 100), 194 (83), 166 (12), 139
(
7), 97 (8), 91 (6), 84 (4), 76 (4), 63 (4), 51 (4). Anal. calcd for C H N O (222.24): C, 75.66; H, 4.54; N, 12.60. Found: C, 75.80; H, 4.86; N,
14 10 2
1
2.47.
1
-(3,5-dimethylphenyl)-2-phenyl-1,8-naphthyridin-4(1H)-one (5l).

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Starting with 1-(2-chloropyridin-3-yl)-3-phenylprop-2-yn-1-one (3a) (0.150 g, 0.62 mmol), Pd(PPh ) (0.072 g, 0.062 mmol), K CO (0.171 g,
3
4
2
3
1
1
5
.24 mmol) and 3,5-dimethylaniline (0.15 mL, 1.24 mmol) in DMF (10 mL), product 5l was isolated as a brown solid (0.083 g, 41 %); mp 188-
1
90 °C; Procedure B. H NMR (CDCl , 300 MHz):  = 2.15 (s, 6H, CH ), 6.41 (s, 1H, H ), 6.67 (s, 2H, H ), 6.81 (s, 1H, H ), 7.09-7.16 (m,
3
3
Ar
Ar
Ar
3
3
4
3
4
3
H, H ), 7.25-7.29 (dd, J = 4.5 Hz, J = 8.0 Hz, 1H, H ), 8.58 (dd, J = 2.0 Hz, J = 4.5 Hz, 1H, H ), 8.71 (dd, J = 2.0 Hz, J = 8.0 Hz, 1H,
Ar
Ar
Ar
1
3
15
H ). C NMR (CDCl , 63 MHz):   21.1, 113.4, 119.9, 120.8, 127.7, 127.8, 128.7, 128.9, 130.1, 135.6, 138.4, 138.5, 152.0, 152.6, 155.4,
Ar
3
–
1
~
1
1

78.1. IR (ATR, cm ): = 3054 (w), 3040 (w), 3010 (w), 2918 (w), 2852 (w), 1633 (s), 1615 (m), 1592 (s), 1558 (w), 1492 (w), 1479 (m),
445 (w), 1405 (s), 1377 (w), 1338 (w), 1295 (m), 1248 (w), 1226 (w), 1175 (w), 1135 (w), 1108 (w), 1077 (w), 1037 (w), 1027 (w).
+
m/z (%) = 325 (M-H , 100), 297 (5), 282 (5), 223 (3), 195 (4), 163 (2), 140 (2), 103 (2), 77 (3). Anal. calcd for C H N O (326.39): C, 80.96; H,
2
2
18
2
5
.56; N, 8.58. Found: C, 80.56; H, 4.45; N, 8.55.
1
-(3-methoxyphenyl)-2-phenyl-1,8-naphthyridin-4(1H)-one (5m).
Starting with 1-(2-chloropyridin-3-yl)-3-phenylprop-2-yn-1-one (3a) (0.150 g, 0.62 mmol), Pd(PPh ) (0.072 g, 0.062 mmol), K CO (0.171 g,
3
4
2
3
1
2
7
.24 mmol) and 3-methoxylaniline (0.14 mL, 1.24 mmol) in DMF (10 mL), product 5m was isolated as a white solid (0.126 g, 62 %); mp 254-
1
55 °C; Procedure B. H NMR (CDCl , 250 MHz):  = 3.62 (s, 1H, OCH ), 6.41 (s, 1H, C=CH), 6.59-6.61 (m, 1H, H ), 6.68-6.76 (m, 2H, H ),
3
3
Ar
Ar
4
3
4
3
13
.12-7.17 (m, 6H, H ), 7.26-7.30 (m, 1H, H ), 8.57 (dd, J = 2.0 Hz, J = 7.9 Hz, 1H, H ), 8.70 (dd, J = 2.0 Hz, J = 4.5 Hz, 1H, H ). C
Ar
Ar
Ar
Ar
NMR (CDCl , 63 MHz): δ = 55.4, 113.5, 114.1, 116.1, 120.0, 120.8, 122.5, 128.0, 128.9, 128.9, 129.3, 135.5, 135.7, 139.8, 151.9, 152.5, 155.1,
3

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–1
~
1

59.8, 178.2. IR (ATR, cm ): = 3049 (w), 3037 (w), 3007 (w), 2963 (w), 2936 (w), 2837 (w), 1632 (s), 1602 (m), 1593 (m), 1574 (w), 1545
(w), 1480 (m), 1439 (w), 1427 (w), 1405 (s), 1336 (w), 1310 (w), 1280 (m), 1244 (m), 1222 (s), 1189 (w), 1171 (m), 1147 (w), 1138 (w), 1084
+
(
w), 1049 (m), 1038 (m). m/z (%) = 327 (M-H , 100), 312 (6), 184 (3), 255 (4), 211 (2), 155 (3), 128 (3), 113 (3), 98 (2), 77 (2). Anal. calcd for
C H N O (328.36): C, 76.81; H, 4.91; N, 8.53. Found: C, 76.78 ; H, 5.02 ; N, 8.34.
21
16
2
2
1
6
1
-(2,4-dimethoxyphenyl)-2-phenyl-1,8-naphthyridin-4(1H)-one (5n).
Starting with 1-(2-chloropyridin-3-yl)-3-phenylprop-2-yn-1-one (3a) (0.150 g, 0.62 mmol), Pd(PPh ) (0.072 g, 0.062 mmol), K CO (0.171 g,
3
4
2
3
1
.24 mmol) and 2,4-dimethoxylaniline (0.18 mL, 1.24 mmol) in DMF (10 mL), product 5n was isolated as a white-brown solid (0.138 g, 62 %);
1
mp 150-152 °C; Procedure B. H NMR (CDCl , 300 MHz):  = 3.53 (s, 3H, OCH ), 3.69 (s, 3H, OCH ), 6.27-6.35 (m, 2H, H ), 6.39 (s, 1H,
3
3
3
Ar
3
4
3
3
C=CH), 6.93 (d, J = 8.6 Hz, 1H, H ), 7.12-7.16 (m, 5H, H ), 7.23-7.27 (dd, J = 4.5 Hz, J = 7.8 Hz, 1H, H ), 8.56 (dd, J = 4.5 Hz,
Ar
Ar
Ar
4
3
4
13
J = 2.0 Hz, 1H, H ), 8.69 (dd, J = 7.9 Hz, J = 2.0 Hz, 1H, H ). C-NMR (CDCl , 63 MHz) : = 55.4, 55.4, 99.1, 104.2, 113.0, 115.8, 119.8,
Ar
Ar
3
–
1
~
1
2
1
20.9, 127.6, 128.4, 128.8, 131.3, 135.5, 135.6, 152.0, 152.6, 156.0, 156.3, 160.9, 178.6. IR (ATR, cm ):  = 3064 (w), 3006 (w), 2962 (w),
928 (w), 2835 (w), 1627 (s), 1589 (m), 1510 (m), 1477 (m), 1455 (w), 1436 (w), 1423 (w), 1405 (s), 1314 (w), 1276 (m), 1255 (w), 1244 (m),
+
211 (s), 1161 (s), 1135 (m), 1098 (w), 1044 (w), 1028 (m). m/z (%) = 358 (M , 4), 327 (100), 312 (5), 283 (2), 197 (3), 163 (3), 128 (3). Anal.
calcd for C H N O (358.39): C, 73.73; H, 5.06; N, 7.82. Found: C, 73.55; H, 4.93; N, 7.71.
2
2
18
2
3

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1
-(4-chlorophenyl)-2-phenyl-1,8-naphthyridin-4(1H)-one (5o).
1
7
Starting with 1-(2-chloropyridin-3-yl)-3-phenylprop-2-yn-1-one (3a) (0.150 g, 0.62 mmol), Pd(PPh ) (0.072 g, 0.062 mmol), K CO (0.171 g,
3
4
2
3
1
.24 mmol) and 4-chloroaniline (0.158 g, 1.24 mmol) in DMF (10 mL), product 5o was isolated as a white solid (0.083 g, 40 %); mp 243-244
1
4
3
°
C; Procedure B. H NMR (CDCl , 250 MHz):  = 6.42 (s, 1H, C=CH), 7.00-7.31 (m, 10H, H ), 8.55 (dd, J = 2.1 Hz, J = 4.5 Hz, 1H, H ),
3
Ar
Ar
4
3
13
8
1
1
1
2
3
.70 (dd, J = 2.0 Hz, J = 8.0 Hz, 1H, H ). C NMR (CDCl , 75 MHz):   113.7, 120.2, 120.8, 128.2, 129.0, 129.0, 129.0, 131.4, 134.2,
Ar
3
–
1
~
35.1, 135.8, 137.3, 151.8, 152.4, 154.8, 178.1. IR (ATR, cm ):

= 3061 (w), 3049 (w), 3031 (w), 2963 (w), 2918 (w), 2849 (w), 1630 (s),
611 (m), 1591 (m), 1573 (m), 1546 (m), 1491 (m), 1476 (s), 1445 (w), 1410 (m), 1399 (s), 1338 (w), 1308 (w), 1272 (m), 1240 (w), 1180 (w),
+
37
+ 35
136 (w), 1095 (w), 1085 (w), 1040 (w), 1031 (w), 1022 (m). m/z (%) = 333 (41, M-H , Cl), 331 (100, M-H , Cl), 295 (9), 268 (15), 229 (6),
3
14
5
+
37
20 14
+
01 (5), 166 (4), 134 (5), 111 (3), 75 (5). HRMS (ESI): calcd for C H ClN O ([M+H] ) 333.0796, found 333.0789, C H ClN O ([M+H] )
2
0
2
2
35.0767, found 335.0771.
1
-(4-bromophenyl)-2-phenyl-1,8-naphthyridin-4(1H)-one (5p).

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
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1
8
Starting with 1-(2-chloropyridin-3-yl)-3-phenylprop-2-yn-1-one (3a) (0.150 g, 0.62 mmol), Pd(PPh ) (0.072 g, 0.062 mmol), K CO (0.171 g,
3
4
2
3
1
.24 mmol) and 4-bromoaniline (0.213 g, 1.24 mmol) in DMF (10 mL), product 5p was isolated as a white solid (0.082 g, 35 %); mp 223-225
1
°
C; Procedure B. H NMR (CDCl , 250 MHz):  = 6.42 (s, 1H, C=CH), 6.94-6.97 (m, 2H, H ), 7.08-7.17 (m, 4H, H ), 7.27-7.38 (m, 4H, H ),
3
Ar
Ar
Ar
4
3
4
3
13
8
1
1
1
.54 (dd, J = 2.0 Hz, J = 4.4 Hz, 1H, H ), 8.70 (dd, J = 2.0 Hz, J = 8.0 Hz, 1H, H ). C NMR (CDCl , 63 MHz):   112.5, 120.3, 120.5,
Ar
Ar
3
–
1
~
21.3, 128.1, 129.0, 129.2, 131.6, 132.8, 135.0, 135.3, 138.5, 151.7, 152.7, 154.8, 176.8. IR (ATR, cm ):

= 3058 (w), 3028 (w), 1730 (w),
630 (s), 1610 (w), 1592 (m), 1545 (w), 1489 (m), 1477 (m), 1444 (w), 1410 (m), 1402 (m), 1336 (w), 1308 (m), 1271 (m), 1183 (w), 1155 (w),
+
81
+ 79
136 (w), 1070 (w), 1040 (w), 1031 (w), 1019 (w). m/z (%) = 379 (95, M , Br), 377 (100, M , Br), 295 (21), 268 (29), 247 (4), 207 (5), 167
(
9), 148 (19), 102 (5), 76 (8), 63 (3), 44 (5). Anal. calcd for C H BrN O (377.23): C, 63.68; H, 3.47; N, 7.43. Found: C, 63.72; H, 3.65; N,
20 13 2
7
.44.
1
-benzyl-2-propyl-1,8-naphthyridin-4(1H)-one (5q).

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Starting with 1-(2-chloropyridin-3-yl)hex-2-yn-1-one (3c) (0.129 g, 0.62 mmol), K CO (0.171 g, 1.24 mmol) and benzylamine (0.14 mL, 1.24
2
3
1
mmol) in DMF (10 mL), product 5q was isolated as a white solid (0.161 g, 93 %); mp 82-84 °C; Procedure A. H NMR (CDCl , 250 MHz):
3
3
3

= 0.92 (t, J = 7.4 Hz, 3H, CH ), 1.57-1.69 (m, 2H, CH ), 2.58 (t, J = 7.4 Hz, 2H, CH ), 5.80 (s, 2H, CH ), 6.34 (s, 1H, C=CH), 6.92-6.94 (m,
3
2
2
2
4
3
4
3
13
2
H, H ), 7.22-7.29 (m, 4H, H ), 8.58 (dd, J = 1.9 Hz, J = 4.5 Hz, 1H, H ), 8.66 (dd, J = 2.0 Hz, J = 8.0 Hz, 1H, H ). C NMR (CDCl , 75
Ar
Ar
Ar
Ar
3
–
1
~
MHz): δ = 18.7, 26.6, 39.7, 51.9, 115.9, 125.2, 125.4, 130.8, 132.3, 133.9, 140.3, 142.9, 155.8, 157.6, 161.7, 181.3. IR (ATR, cm ):

= 3058
1
9
(w), 3030 (w), 2960 (w), 2929 (w), 2870 (w), 1681 (w), 1618 (m), 1592 (m), 1546 (w), 1492 (m), 1452 (w), 1426 (w), 1412 (m), 1363 (w), 1307
+
(
w), 1278 (w), 1244 (w), 1227 (w), 1188 (w), 1138 (w), 1119 (m), 1049 (w), 1028 (w), 1000 (w). m/z (%) = 278 (M , 87), 263 (20), 250 (28),
2
35 (6), 187 (37), 91 (100), 65 (13). Anal. calcd for C H N O (278.35): C, 77.67; H, 6.52; N, 10.06. Found: C, 77.83 ; H, 6.49 ; N, 10.07.
18 18 2
1
-cyclohexyl-2-propyl-1,8-naphthyridin-4(1H)-one (5r).
Starting with 1-(2-chloropyridin-3-yl)hex-2-yn-1-one (3c) (0.129 g, 0.62 mmol), K CO (0.171 g, 1.24 mmol) and cyclohexylamine (0.14 mL,
2
3
1
1
2
.24 mmol) in DMF (10 mL), product 5r was isolated as a white solid (0.163 g, 97 %); mp 114-116 °C; Procedure A. H NMR (CDCl ,
3
3
3
50 MHz):  = 1.02 (t, J = 7.4 Hz, 3H, CH ), 1.28-1.34 (m, 3H, CH ), 1.61-1.73 (m, 5H, CH ), 1.87-1.90 (m, 2H, CH ), 2.68 (t, J = 7.4 Hz, 2H,
3
2
2
2
1
3
CH ), 3.00-3.13 (m, 2H, CH ), 4.12-4.20 (m, 1H, CH
), 6.28 (s, 1H, C=CH), 7.22-7.24 (m, 1H, H ), 8.58-8.65 (m, 2H, H ). C-NMR
Ar Ar
2
2
Cyclohexyl
–
1
~
(
CDCl , 63 MHz): δ = 13.4, 21.7, 24.9, 26.0, 30.0, 36.3, 60.4, 111.5, 119.4, 120.8, 134.5, 150.7, 151.1, 156.3, 175.7. IR (ATR, cm ):

= 3076
3
(w), 3020 (w), 2961 (w), 2916 (w), 2862 (w), 2849 (w), 1623 (s), 1589 (s), 1571 (m), 1547 (w), 1483 (m), 1459 (w), 1435 (w), 1415 (m), 1389

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+
(
m), 1380 (m), 1337 (w), 1299 (w), 1287 (w), 1258 (w), 1244 (w), 1225 (w), 1199 (w), 1149 (w), 1117 (s), 1048 (w). m/z (%) = 270 (M , 17),
+
1
88 (44), 173 (13), 160 (100), 131 (8), 78 (4), 55 (4). HRMS (ESI): calcd for C H N O ([M+H] ) 271.18049, found 271.18042.
17 23 2
2
-(4-tert-butylphenyl)-1-phenethyl-1,8-naphthyridin-4(1H)-one (5s).
2
0
Starting with 3-(4-tert-butylphenyl)-1-(2-chloropyridin-3-yl)prop-2-yn-1-one (3b) (0.185 g, 0.62 mmol), K CO (0.171 g, 1.24 mmol) and
2
3
2
-phenylethylamine (0.16 mL, 1.24 mmol) in DMF (10 mL), product 5s was isolated as a white solid (0.232 g, 98 %); mp 202-204 °C;
1
3
3
Procedure A. H NMR (CDCl , 300 MHz):  = 1.33 (s, 9H, C(CH ) ), 2.82 (t, J = 7.9 Hz, 2H, CH ), 4.48 (t, J = 7.9 Hz, 2H, CH ), 6.25 (s, 1H,
3
3 3
2
2
C=CH), 6.70- 6.73 (m, 2H, H ), 7.07-7.11 (m, 3H, H ), 7.16-7.19 (m, 2H, H ), 7.30-7.35 (m, 1H, H ), 7.41-7.45 (m, 2H, H ), 8.70 (dd,
Ar
Ar
Ar
Ar
Ar
4
3
4
3
13
J = 2.0 Hz, J = 8.0 Hz, 1H, H ), 8.75 (dd, J = 2.0 Hz, J = 4.0 Hz, 1H, H ). C NMR (CDCl , 63 MHz): δ = 31.3, 34.9, 35.6, 48.0, 113.5,
Ar
Ar
3
–
1
~
1
3
1
19.7, 121.6, 125.5, 126.5, 128.1, 128.4, 128.7, 132.4, 135.8, 138.0, 150.5, 152.2, 152.8, 155.5, 177.6. IR (ATR, cm ):  = 3051 (w), 3028 (w),
000 (w), 2960 (w), 2902 (w), 2867 (w), 1622 (s), 1601 (w), 1589 (s), 1556 (w), 1504 (w), 1468 (m), 1451 (w), 1431 (w), 1414 (s), 1366 (w),
332 (w), 1313 (w), 1299 (w), 1257 (w), 1246 (w), 1232 (m), 1197 (w), 1188 (w), 1134 (m), 1110 (w), 1049 (w), 1038 (w), 1027 (w).
+
m/z (%) = 382 (M , 7), 291 (3), 278 (100), 263 (25), 235 (91), 205 (3), 133 (5), 106 (8), 91 (3), 78 (7), 57 (16). Anal. calcd for C H N O
2
6
26
2
(383.50): C, 81.64; H, 6.85; N, 7.32. Found: C, 81.42; H, 6.63; N, 7.50.
2
-(4-tert-butylphenyl)-1-cyclohexyl-1,8-naphthyridin-4(1H)-one (5t).

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2
1
Starting with 3-(4-tert-butylphenyl)-1-(2-chloropyridin-3-yl)prop-2-yn-1-one (3b) (0.185 g, 0.62 mmol), K CO (0.171 g, 1.24 mmol) and
2
3
2
- cyclohexylamine (0.14 mL, 1.24 mmol) in DMF (10 mL), product 5t was isolated as a white solid (0.210 g, 94 %); mp 185-187 °C; Procedure
1
A. H NMR (CDCl , 300 MHz):  = 0.83-0.97 (m, 4H, CH ), 1.32 (s, 9H, C(CH ) ), 1.52-1.73 (m, 4H, CH ), 2.84-3.00 (m, 2H, CH ), 3.99-4.08
3
2
3 3
2
2
1
3
(
m, 1H, CHCyclohexyl), 6.18 (s, 1H, C=CH), 7.19-7.27 (m, 3H, H ), 7.42-7.45 (m, 2H, H ), 8.64-8.67 (m, 2H, H ). C NMR (CDCl , 63 MHz):
Ar Ar Ar 3
–
1
~

3
1

  25.2, 26.6, 30.7, 31.3, 34.8, 63.9, 113.8, 119.4, 122.2, 125.6, 127.4, 133.8, 135.5, 150.8, 151.6, 152.7, 156.7, 177.6. IR (ATR, cm ): =
041 (w), 2957 (w), 2925 (w), 2852 (w), 1639 (s), 1589 (m), 1556 (w), 1506 (w), 1486 (m), 1456 (w), 1431 (w), 1397 (m), 1363 (w), 1337 (w),
+
303 (w), 1255 (w), 1230 (w), 1201 (w), 1140 (w), 1127 (w), 1109 (w), 1063 (w), 1044 (w), 1024 (w). m/z (%) = 360 (M , 10), 278 (100), 263
(
66), 235 (9), 207 (4), 117 (4), 103 (3), 78 (2), 55 (3), 41 (3). Anal. calcd for C H N O (360.49): C, 79.96; H, 7.83; N, 7.77. Found: C, 80.19;
24 28 2
H, 7.75; N, 7.45.
2
-(4-tert-butylphenyl)-1-phenyl-1,8-naphthyridin-4(1H)-one (5u).

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Starting with 3-(4-tert-butylphenyl)-1-(2-chloropyridin-3-yl)prop-2-yn-1-one (3b) (0.185 g, 0.62 mmol), K CO (0.171 g, 1.24 mmol) and
2
3
1
aniline (0.11 mL, 1.24 mmol) in DMF (10 mL), product 5u was isolated as a white solid (0.092 g, 42 %); mp 247-249 °C; Procedure B. H
4
NMR (CDCl , 300 MHz):  = 1.16 (s, 9H, C(CH ) ), 6.44 (s, 1H, C=CH), 7.00-7.14 (m, 6H, H ), 7.19-7.29 (m, 4H, H ), 8.54 (dd, J = 2.0 Hz,
3
3 3
Ar
Ar
3
4
3
13
J = 4.6 Hz, 1H, H ), 8.71 (dd, J = 2.0 Hz, J = 7.9 Hz, 1H, H ). C NMR (CDCl , 63 MHz):   31.1, 34.6, 113.5, 119.9, 120.8, 124.8,
Ar
Ar
3
–
1
~
1
2
1

28.2, 128.6, 128.8, 130.1, 132.5, 135.6, 138.9, 152.0, 152.0, 152.4, 155.4, 178.2. IR (ATR, cm ): = 3062 (w), 3049 (w), 2961 (w), 2902 (w),
2
2
866 (w), 1635 (s), 1613 (w), 1594 (m), 1577 (w), 1506 (w), 1495 (m), 1477 (m), 1410 (s), 1361 (w), 1338 (w), 1305 (w), 1270 (m), 1202 (w),
+
178 (w), 1155 (w), 1134 (w), 1115 (w), 1037 (w), 1025 (w). m/z (%) = 353 (M-H , 100), 339 (19), 297 (4), 197 (6), 155 (8), 140 (2), 77 (3).
Anal. calcd for C H N O (354.44): C, 81.33; H, 6.26; N, 7.90. Found: C, 81.55 ; H, 6.31 ; N, 7.70.
2
4
22
2
1
-benzyl-1,8-naphthyridin-4(1H)-one (5v).
Starting with 1-(2-chloropyridin-3-yl)-3-(trimethylsilyl)prop-2-yn-1-one (3e) (0.147 g, 0.62 mmol), K CO (0.171 g, 1.24 mmol) and
2
3
benzylamine (0.14 mL, 1.24 mmol) in DMF (10 mL) at 100 °C, product 5v was isolated as a white solid (0.119 g, 81 %); mp 113-115 °C;
1
3
Procedure A. H NMR (CDCl , 300 MHz):  = 5.62 (s, 2H, CH ), 6.19 (d, J = 7.9 Hz, 1H, C=CH-C=O), 7.27-7.32 (m, 5H, H ), 7.41-7.45 (m,
3
2
Ar
4
3
3
4
3
4
J = 4.5 Hz, J = 8.0 Hz, 1H, H ), 8.20 (d, J = 7.9 Hz, 1H, C=CH-N), 8.52 (dd, J = 2.0 Hz, J = 8.0 Hz, 1H, H ), 8.76 (dd, J = 2.0 Hz,
Ar
Ar
3
13
J = 4.5 Hz, 1H, H ). C NMR (CDCl , 63 MHz): δ = 51.8, 110.1, 119.6, 121.1, 127.0, 127.2, 128.3, 135.0, 137.1, 144.2, 149.5, 152.1, 176.9.
Ar
3
–
1
~
IR (ATR, cm ):
 = 3060 (w), 3047 (w), 3025 (w), 2991 (w), 2952 (w), 2923 (w), 2850 (w), 1643 (w), 1617 (s), 1580 (s), 1551 (w), 1489 (m),
1
454 (w), 1434 (m), 1412 (m), 1401 (m), 1358 (w), 1327 (w), 1300 (w), 1289 (w), 1252 (w), 1235 (s), 1216 (w), 1184 (w), 1155 (w), 1135 (w),

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+
1
120 (w), 1085 (w), 1047 (w), 1027 (w). m/z (%) = 236 (M , 79), 207 (4), 117 (2), 91 (100), 65 (12), 51 (4). Anal. calcd for C H N O
15 12 2
(236.27): C, 76.25; H, 5.12; N, 11.86. Found: C, 76.31 ; H, 5.42 ; N, 11.44.
1
-phenethyl-1,8-naphthyridin-4(1H)-one (5w).
2
3
Starting with 1-(2-chloropyridin-3-yl)-3-(trimethylsilyl)prop-2-yn-1-one (3e) (0.147 g, 0.62 mmol), K CO (0.171 g, 1.24 mmol) and 2-
2
3
phenylethylamine (0.16 mL, 1.24 mmol) in DMF (10 mL) at 100 °C, product 5w was isolated as a white solid (0.101 g, 65 %); mp 98-100 °C;
1
3
3
3
Procedure A. H NMR (CDCl , 300 MHz):  = 3.06 (t, J = 7.0 Hz, 2H, CH ), 4.50 (t, J = 7.0 Hz, 2H, CH ), 6.07 (d, J = 7.9 Hz, 1H, C=CH),
3
2
2
4
3
4
7
.00-7.03 (m, 2H, H ), 7.12-7.17 (m, 2H, H ), 7.12-7.30 (m, 3H, H ), 8.64 (dd, J = 2.0 Hz, J = 8.0 Hz, 1H, H ), 8.69 (dd, J = 2.0 Hz,
Ar
Ar
Ar
Ar
3
13
J = 4.5 Hz, 1H, H ). C NMR (CDCl , 63 MHz): δ = 35.7, 52.7, 110.5, 119.7, 121.9, 126.9, 128.7, 128.9, 136.0, 137.7, 143.4, 149.6, 152.3,
Ar
3
–
1
~
1
1
1
78.7.IR (ATR, cm ):

= 3040 (w), 3028 (w), 2958 (w), 2944 (w), 2864 (w), 1616 (s), 1600 (w), 1579 (s), 1485 (s), 1454 (w), 1429 (m),
409 (s), 1393 (w), 1370 (w), 1312 (w), 1298 (w), 1286 (w), 1264 (m), 1239 (s), 1224 (m), 1199 (w), 1190 (m), 1151 (w), 1128 (w), 1084 (w),
+
048 (w), 1031 (w), 1023 (w). m/z (%) = 250 (M , 12), 159 (54), 146 (100), 133 (8), 118 (10), 106 (9), 91 (6), 78 (11), 65 (4), 51 (5). Anal. calcd
for C H N O (250.29): C, 76.78; H, 5.64; N, 11.19. Found: C, 76.72 ; H, 5.64 ; N, 11.18.
1
6
14
2
1
-(3-(trifluoromethyl)phenyl)-2-phenyl-1,8-naphthyridin-4(1H)-one (5x)

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O
N
N
CF3
24
0
1
Yellow solid, mp 207-209 C. H NMR (300 MHz, CDCl ): δ = 6.49 (s, 1H, CH ), 7.12-7.21 (m, 2H, CH ), 7.34-7.53 (m, 7H, CH ), 7.62-7.69
m, 1H, CH ), 8.57-8.60 (m, 1H, CH ), 8.77 (dd, 1H, J = 7.9 Hz, J = 2.0 Hz, CH ).
F NMR (282 MHz, CDCl ): δ = -62.9.
C NMR (75.5 MHz, CDCl ): δ = 113.8, 120.3 (CH), 123.3 (q, J = 273 Hz, CF ), 124.9 (q, J = 3.7 Hz, CHCCF ), 127.4 (q, J = 3.7 Hz,
3
Ar
Ar
Ar
3
4
(
Ar
Ar
Ar
1
9
3
1
3
1
3
3
3
3
3
2
CHCCF ), 128.2, 128.4, 128.6, 128.9, 129.1 (CH), 131.3 (q, J = 32 Hz, CCF ), 131.9 (C), 132.0, 132.1 (CH), 134.9 (C), 139.4, 151.6 (C), 152.4
3
3
(
CH), 154.7, 178.2 (C).
+
MS (GC, 70eV): m/z (%) = 366 (M , 100).
HRMS (EI): calcd for C H F N O (M ) 366.33593, found 366.33595.
IR (ATR, cm ):
+
2
1
13
3
2
-1
~

= 3057 (w), 1636 (s), 1593 (m), 1496 (m), 1477 (m), 1446 (m), 1404 (s), 1328 (s), 1304 (m), 1265 (m), 1170 (s), 1137 (m),
1
116 (s), 1074 (s), 1042 (m), 989 (m), 928 (w), 846 (m), 829 (m), 813 (m), 769 (s), 721 (s), 699 (s), 653 (s), 540 (s).
1
-(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)-3-phenylprop-2-yn-1-one (9)
O
Me
N
Cl
N
1
13
Brown solid 80%. Mp 78 C; H NMR (300 MHz, DMSO-d ) δ 2.64 (s, 3H, Me), 7.37–7.57 (m, 8H), 7.62-7.65 (m, 2H); C NMR (75 MHz,
6
DMSO-d ) δ 15.4, 88.3, 92.4, 118.2, 120.3, 125.6, 128.6, 129.1, 130.7, 131.6, 132.8, 137.2, 152.4, 164.0, 170.3. MS (GC, 70 eV) m/z (%) 320
6

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+
+
–1
~
(
M , 46), 319 (100), 189 (11), 129 (15), 77 (31); HRMS (EI): calcd for C H ClN O (M ) 320.07125, found 320.07127; IR (ATR, cm )

19
13
2
3
1
035 (w), 2199 (m), 1620 (s), 1520 (m), 1489 (m), 1462 (s), 1415 (m), 1382 (m), 1369 (s), 1299 (m), 1205 (w), 1101 (w), 1072 (w), 1027 (m),
014 (m), 986 (s), 907 (w), 815 (w), 786 (m), 752 (s), 684 (s), 645 (m), 605 (s).
3
-(4-methoxybenzylamino)-1-(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)-3-phenylprop-2-en-1-one (10)
2
5
OMe
HN
O
Ph
Me
N
Cl
N
Ph
1
3
Wiht solid 60%. mp 155-157C; H NMR (300 MHz, DMSO-d ) δ 2.40 (s, 3H, Me), 2.40 (s, 3H, OMe), 4.34 (d, 1H, J = 6.3 Hz, CH ), 5.60 (s,
6
2
3
13
1
4
4
1
8
H, OCCH), 6.89-6.92 (m, 2H), 7.13-7.16 (m, 2H), 7.48-7.55 (m, 10H), 11.35 (t, 1H, J = 6.3 Hz, NH); C NMR (75 MHz, DMSO-d ) δ 14.5,
6
7.1, 55.0, 96.2, 114.0, 119.0, 120.0, 127.6, 128.5, 128.7, 129.1, 129.7, 130.3, 134.8, 137.4, 149.6, 158.6, 165.5, 181.9. MS (GC, 70 eV) m/z (%)
+
+
–1
~
57 (M , 4), 422 (100), 121 (65); HRMS (EI): calcd for C H ClN O (M ) 457.1632, found 457.1634; IR (ATR, cm )

2928 (w), 1607 (w),
2
7
24
3
2
557 (m), 1506 (m), 1484 (m), 1454 (m), 1411 (m), 1361 (m), 1303 (m), 1250 (m), 1182 (m), 1141 (w), 1104 (w), 1070 (w), 1033 (m), 889 (w),
18 (m), 774 (s), 736 (m), 697 (s), 613 (w).
(Z)-3-(3-(trifluoromethyl)phenylamino)-1-(2-chloropyridin-3-yl)-3-phenylprop-2-en-1-one (11)

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O
HN
CF3
N
Cl
1
Yellow solid 61%. mp 183-185C; H NMR (300 MHz, CDCl ) δ 5.84 (s, 1H, CCHC), 6.89-6.92 (m, 1H), 6.98 (br.s, 1H), 7.19-7.21 (m, 2H),
26
3
3
4
3
4
19
7
.26-7.35 (m, 6H), 7.87 (dd, 1H, J = 7.5 Hz, J = 2.0 Hz), 8.38 (dd, 1H, J = 4.7 Hz, J = 1.9 Hz), 12.61 (s, 1H, NH); F NMR (282 MHz,
13
3
3
1
CDCl ) δ -63.1; C NMR (75 MHz, CDCl ) δ 101.3, 119.9 (q, J = 3.8 Hz), 121.0 (q, J = 3.8 Hz), 122.4, 123.4 (q, J = 272.2 Hz), 126.2,
3
3
2
+
1
3
1
1
28.3, 128.9, 129.3, 130.4, 131.3 (q, J = 30.7 Hz), 134.2, 136.8, 138.4, 139.6, 147.6, 150.2, 161.6, 189.1. MS (GC, 70 eV) m/z (%) 402 (M ,
+
–1
~
0), 367 (100), 290 (63), 262 (73), 145 (20); HRMS (EI): calcd for C H F N O (M ) 402.0719, found 402.0721; IR (ATR, cm )

2196 (w),
2
1
14
3
2
593 (m), 1567 (s), 1514 (m), 1490 (w), 1471 (m), 1451 (m), 1392 (m), 1307 (s), 1265 (m), 1222 (m), 1161 (m), 1124 (s), 1098 (s), 1064 (m),
037 (m), 999 (m), 891 (m), 871 (m), 799 (m), 763 (s), 729 (m), 697 (s), 656 (m), 639 (s).
3
-bromo-1-cyclohexyl-2-phenyl-1,8-naphthyridin-4(1H)-one (20).
Starting with 1-cyclohexyl-2-phenyl-1,8-naphthyridin-4(1H)-one (5e) (0.600 g, 1.97 mmol), Br (0.15 mL, 2.96 mmol) and Na CO (1.252 g,
2
2
3
1
1
1.82 mmol) in THF (30 mL), product 20 was isolated as a white solid (0.680 g, 90 %); mp 253-255 °C; Procedure C. H NMR (CDCl ,
3

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2
2
8
1
1
1
5
50 MHz):  = 0.73-0.86 (m, 2H, HCyclohexyl), 1.09-1.18 (m, 1H, HCyclohexyl), 1.43-1.48 (m, 1H, HCyclohexyl), 1.59-1.69 (m, 4H, HCyclohexyl), 2.89-
4
3
.93 (m, 2H, HCyclohexyl), 3.87 (m, 1H, HCyclohexyl), 7.22-7.32 (m, 3H, H ), 7.47-7.54 (m, 3H, H ), 8.68 (dd, J = 2.1 Hz, J = 4.3 Hz, 1H, H ),
Ar
Ar
Ar
4
3
13
.74 (dd, J = 2.1 Hz, J = 7.9 Hz, 1H, H ). C NMR (CDCl , 63 MHz): δ = 25.0, 26.6, 30.5, 66.0, 109.9, 120.0, 120.1, 127.3, 129.2, 129.6,
Ar
3
–
1
~
36.4, 136.8, 150.3, 151.2, 154.0, 172.8 IR (ATR, cm ):

= 3045 (w), 2997 (w), 2929 (w), 2866 (w), 2842 (w), 1620 (s), 1590 (s), 1575 (m),
529 (w), 1483 (m), 1444 (w), 1425 (w), 1414 (w), 1383 (m), 1332 (w), 1310 (w), 1264 (w), 1235 (s), 1156 (w), 1128 (m), 1094 (w), 1059 (w),
+
81
+
79
81
79
27
046 (m). m/z (%) = 384 (M-H , 14, Br), 382 (M-H , 14, Br), 302 (98, Br), 300 (100, Br), 274 (18), 221 (35), 192 (18), 166 (18), 139 (5),
5 (7), 41 (7). Anal. calcd for C H BrN O (383.28): C, 62.67; H, 5.00; N, 7.31. Found: C, 62.71 ; H, 5.01 ; N, 7.43.
2
0
19
2
1
-cyclohexyl-2,3-diphenyl-1,8-naphthyridin-4(1H)-one (21a).
Starting with 3-bromo-1-cyclohexyl-2-phenyl-1,8-naphthyridin-4(1H)-one (20) (0.150 g, 0.39 mmol), Pd(PPh ) (0.023 g, 0.020 mmol), K CO
3
3
4
2
(0.108 g, 0.78 mmol) and phenylboronic acid (0.052 g, 0.43 mmol) in DMF (10 mL), product 21a was isolated as a white solid (0.089 g, 60 %);
1
mp 215-218 °C; Procedure D. H NMR (CDCl , 250 MHz):  = 0.74-0.87 (m, 2H, HCyclohexyl), 1.15-1.21 (m, 1H, HCyclohexyl), 1.44-1.48 (m, 1H,
3
HCyclohexyl), 1.65-1.69 (m, 4H, HCyclohexyl), 2.90-3.02 (m, 2H, HCyclohexyl), 3.84-3.91 (m, 1H, HCyclohexyl), 6.91-7.10 (m, 7H, H ), 7.17-7.21 (m, 3H,
Ar
3
3
4
3
4
3
13
H ), 7.26 (dd, J = 4.4 Hz, J = 8.2 Hz, 1H, H ), 8.67 (dd, J = 2.1 Hz, J = 4.5 Hz, 1H, H ), 8.72 (dd, J = 2.1 Hz, J = 8.0 Hz, 1H, H ). C
Ar
Ar
Ar
Ar
NMR (CDCl , 75 MHz): δ = 25.2, 26.7, 30.6, 64.3, 119.4, 121.8, 125.2, 126.2, 127.5, 128.2, 128.6, 128.7, 131.2, 135.5, 135.7, 136.1, 150.8,
3
–
1
~
1
1
51.1, 153.7, 176.6. IR (ATR, cm ):
 = 3056 (w), 3030 (w), 2997 (w), 2930 (w), 2853 (w), 1614 (s), 1587 (s), 1537 (m), 1498 (w), 1484 (m),
451 (w), 1444 (w), 1426 (w), 1412 (w), 1394 (m), 1279 (m), 1265 (w), 1252 (w), 1225 (w), 1208 (w), 1177 (w), 1147 (w), 1115 (w), 1075 (w),

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+
1
060 (w), 1043 (w), 1025 (w). m/z (%) = 380 (M , 22), 297 (100), 268 (5), 176 (2), 139 (1), 55 (2), 41 (1). HRMS (ESI): calcd for C H N O
2
6
25
2
+
(
[M+H] ) 381.19614, found 381.19551.
1
-cyclohexyl-3-(4-ethylphenyl)-2-phenyl-1,8-naphthyridin-4(1H)-one (21b).
2
8
Starting with 3-bromo-1-cyclohexyl-2-phenyl-1,8-naphthyridin-4(1H)-one (20) (0.150 g, 0.39 mmol), Pd(PPh ) (0.023 g, 0.020 mmol), K CO
3
3
4
2
(0.108 g, 0.78 mmol) and 4-ethylphenylboronic acid (0.065 g, 0.43 mmol) in DMF (10 mL), product 21b was isolated as a white solid (0.096 g,
1
3
6
1
0 %); mp 195-198 °C; Procedure D. H NMR (CDCl , 250 MHz):  = 0.73-0.86 (m, 2H, H
), 1.03-1.08 (t, J = 7.6 Hz, 3H, CH ), 1.15-
3
Cyclohexyl
3
3
.20 (m, 1H, HCyclohexyl), 1.43-1.47 (m, 1H, HCyclohexyl), 1.65-1.68 (m, 4H, HCyclohexyl), 2.43 (q, J = 7.6 Hz, 2H, CH ), 2.90-3.01 (m, 2H,
2
4
HCyclohexyl), 3.81-3.89 (m, 1H, HCyclohexyl), 6.81-6.87 (m, 4H, H ); 7.06-7.09 (m, 2H, H ), 7.17-7.26 (m, 4H, H ), 8.67 (dd, J = 2.1 Hz,
Ar
Ar
Ar
3
4
3
13
J = 4.5 Hz, 1H, H ), 8.72 (dd, J = 2.1 Hz, J = 8.0 Hz, 1H, H ). C NMR (CDCl , 63 MHz): δ = 15.3, 25.1, 26.7, 28.5, 30.5, 64.2, 119.3,
Ar
Ar
3
–
1
~
1
2
1
1
21.7, 125.2, 127.0, 128.2, 128.4, 128.6, 131.0, 132.7, 135.6, 136.1, 141.8, 150.7, 151.1, 153.6, 176.7. IR (ATR, cm ):  = 3054 (w), 3024 (w),
962 (w), 2869 (w), 2851 (w), 1622 (s), 1589 (s), 1537 (w), 1511 (w), 1484 (m), 1453 (w), 1442 (m), 1407 (w), 1395 (m), 1280 (m), 1265 (m),
+
233 (w), 1212 (w), 1180 (w), 1149 (w), 1114 (w), 1059 (w), 1040 (w), 1022 (w). m/z (%) = 408 (M , 28), 325 (100), 297 (11), 227 (1), 189 (1),
+
65 (1), 55 (2), 41 (1). HRMS (ESI): calcd for C H N O ([M+H] ) 409.22744, found 409.22695.
2
8
29
2
1
-cyclohexyl-2-phenyl-3-(4-(trifluoromethyl)phenyl)-1,8-naphthyridin-4(1H)-one (21c).

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
2
9
Starting with 3-bromo-1-cyclohexyl-2-phenyl-1,8-naphthyridin-4(1H)-one (20) (0.150 g, 0.39 mmol), Pd(PPh ) (0.023 g, 0.020 mmol), K CO
3
3
4
2
(0.108 g, 0.78 mmol) and 4-(trifluoromethyl)phenylboronic acid (0.082 g, 0.43 mmol) in DMF (10 mL), product 21c was isolated as a white
1
solid (0.075 g, 43 %); mp 200-203 °C; Procedure D. H NMR (CDCl , 300 MHz):  = 0.74-0.88 (m, 2H, HCyclohexyl), 1.15-1.21 (m, 1H,
3
HCyclohexyl), 1.44-1.49 (m, 1H, HCyclohexyl), 1.66-1.69 (m, 4H, HCyclohexyl), 2.91-2.98 (m, 2H, HCyclohexyl), 3.86-3.88 (m, 1H, HCyclohexyl), 7.04-7.08
1
9
13
(
m, 4H, H ), 7.21-7.30 (m, 6H, H ), 8.69-8.73 (m, 2H, H ). F (CDCl , 282 MHz)  = -62.54 (CF ). C NMR (CDCl , 63 MHz)  = 25.1,
Ar
Ar
Ar
3
3
3
3
1
2
2
1
1
1
6.6, 30.6, 64.5, 119.7, 121.7, 123.8, 124.3 ( J = 3.8 Hz, C -C -CF ), 124.4 ( J = 271.9 Hz, CF ), 128.2 ( J = 32.4 Hz, C -CF ), 128.5,
CF Ph Ph 3 CF 3 CF Ph 3
–
1
~
29.0, 131.6, 134.9, 136.1, 139.7, 139.7, 151.1, 151.1, 153.9, 176.2. IR (ATR, cm ):

= 3085 (w), 3060 (w), 2990 (w), 2935 (w), 2854 (w),
623 (w), 1609 (m), 1587 (s), 1539 (w), 1516 (w), 1485 (m), 1453 (w), 1448 (w), 1430 (m), 1396 (m), 1321 (s), 1283 (m), 1251 (w), 1228 (w),
+
178 (w), 1160 (m), 1116 (s), 1105 (s), 1064 (s), 1039 (w), 1020 (w). m/z (%) = 448 (M , 17), 365 (100), 295 (2), 268 (3), 55 (2), 41 (2). HRMS
+
(
ESI): calcd for C H F NO ([M+H] ) 449.18352, found 449.18382.
2
7
24 3
References
[
1]
2]
F. C. Fuchs, G. A. Eller, W. Holzer, Molecules 2009, 14, 3814-3832.
Compounds were used, but not isolated (no analytical data are given): B. Willy, W. Frank, T. J. J. Müller, Org. Biomol. Chem. 2010, 8, 90-95.
[

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This journal is © The Royal Society of Chemistry 2012
(C)
UV-Study
-5
The absorption spectra were measured on a Perkin Elmer UV/Vis Spectrometer Lambda 2 in dichloromethane (c ≈ 2.5 * 10 mol/l). The fluorescence spectra
-4
were recorded on a Hitachi F-4010 fluorescence spectrometer in dichloromethane (c = 10 mol/l; excitation wavelength: 350 nm). The solvent was distilled
before use.
3
0
Table 1. Absorption and emission data for of 1,8-naphthyridin-4(1H)-ones.
Compound
λa, max1 /nm
λa, max2 /nm
λa, max3 /nm
λe, max /nm
Stokes Shift
(λe, max – λa, max3 /cm )
-
1
-1
-1
-1
-1
-1
-1
(
ε /L mol cm )
230 (50458)
230 (34092)
230 (53378)
230 (51187)
230 (47339)
(ε /L mol cm )
254 (103142)
260 (81918)
252 (60787)
254 (59285)
256 (54416)
(ε /L mol cm )
348 (43946)
353 (32701)
353 (26922)
351 (30534)
353 (26676)
5
2
e
0
390
395
435
410
420
3095
3012
5340
4100
4519
2
2
1a
1b
2
1c
λa, max1 : wavelength absorption maximum 1.
λa, max2 : wavelength absorption maximum 2.
λa, max3 : wavelength absorption maximum 3.
λe, max : wavelength fluorescence maximum.
-
1
-1
ε
: extinction coefficient (L mol cm ).
The following diagrams show the normalized absorption and emission spectra of the corresponding compounds.
a) Compound 5e