Activation-free one-pot alkynylation–cyclization synthesis of 2-substituted 4-azaindoles and indoles

Article abstract of DOI:10.1007/s10593-018-2269-z

[Figure not available: see fulltext.] 2-Substituted 4-azaindoles and indoles are rapidly and efficiently prepared in an activation-free Pd-catalyzed alkynylation–cyclization sequence starting from 3-amino-2-bromopyridine or o-bromoaniline and terminal alkynes in a one-pot fashion.

Full text of DOI:10.1007/s10593-018-2269-z

DOI 10.1007/s10593-018-2269-z
Chemistry of Heterocyclic Compounds 2018, 54(3), 334–338
Activation-free one-pot alkynylation–cyclization synthesis
of 2-substituted 4-azaindoles and indoles
Timo Lessing1, Thomas J. J. Müller1*
1 Institut für Organische Chemie und Makromolekulare Chemie,
Lehrstuhl für Organische Chemie, Heinrich-Heine-Universität Düsseldorf,
1 Universitätsstraße, D-40225 Düsseldorf, Germany; e-mail: ThomasJJ.Mueller@hhu.de
Published in Khimiya Geterotsiklicheskikh Soedinenii,
2018, 54(3), 334–338
Submitted March 19, 2018
Accepted April 9, 2018
Pd(PPh3)2Cl2, (1-Ad)2PBn·HBr
X
X
Br
DBU, DMSO, 100°C, 0.5–1 h
R
+
HC
R
N
H
then KOt-Bu, DMSO, 100°C, 0.25 h
NH2
23–85%
10 examples
Rapid one-pot
alkynylation–cyclization reaction
without amino activation
X = N, CH
R = Alk, Ar, vinyl
2-Substituted 4-azaindoles and indoles are rapidly and efficiently prepared in an activation-free Pd-catalyzed alkynylation–cyclization
sequence starting from 3-amino-2-bromopyridine or o-bromoaniline and terminal alkynes in a one-pot fashion.
Keywords: 4-azaindoles, heterocycles, indoles, alkynylation, cyclization, one-pot reaction.
Indole1 takes a most prominent position as a hetero-
cyclic core element, and it can be found in numerous both
natural and synthetic biologically active compounds2–6 as
well as in dyes.7 As a consequence, indole syntheses have
become an evergreen topic in synthetic chemistry.8–13 In
particular, Pd-catalyzed routes starting from o-halo-
anilines14 are elegant annulation strategies. Furthermore,
multicomponent syntheses of heterocycles initiated by
transition metal catalysis15–17 as one-pot processes have
received increasing attention in the past decade. Aza-
indoles, i.e., pyrrolopyridines, are the isoelectronic
congeners of indoles, where a CH unit in the benzene ring
is formally replaced by a nitrogen atom. Since kinases have
been identified to be most promising targets18 in controlling
cancer metabolism, privileged scaffolds19–22 for anticancer
agents evolved.23–25 In this capacity, azaindole derivatives26
have turned out to be promising potent inhibitors of various
kinases.27–34 This justifies why, like for indoles, catalytic,
organometallic routes to azaindoles are a constant endeavor
in synthetic chemistry.35–38
Scheme 1. 2-Substituted 7-azaindoles by one-pot Cu-free
Pd-catalyzed alkynylation–cyclization synthesis
component synthesis of 1,2,5-trisubstituted 7-azaindoles.43
Herein, we report the exemplary activating group-free one-
pot alkynylation–cyclization synthesis of 2-substituted
4-azaindoles and indoles.
Based on the optimized protocol for the synthesis of
2-substituted 7-azaindoles19 we applied the developed
conditions, maintaining PdCl2(PPh3)2 as a Pd source and
cataCXium® ABn·HBr ((1-Ad)2PBn·HBr, di(1-adamantyl)-
benzylphosphonium hydrobromide) as a ligand,44,45 for
reacting 3-amino-2-bromopyridine (1a) or o-bromoaniline
(1b) with various terminal alkynes 2a–g. The process
proceeds smoothly and furnishes ten 2-substituted 4-aza-
indoles and indoles 3a–j in moderate to good yields after
isolation (Scheme 2).
Just recently, taking advantage of our copper-free
Pd-catalyzed alkynylation protocol applicable to consecutive
multicomponent syntheses of heterocycles,39–41 we dis-
closed a rapid and efficient activation-free access to 2-sub-
stituted 7-azaindoles in a one-pot alkynylation–cyclization
sequence starting from 2-aminopyridyl halides and terminal
alkynes (Scheme 1).42 This sequence was then developed
further into an alkynylation–cyclization–alkylation three-
0009-3122/18/54(3)-0334©2018 Springer Science+Business Media, LLC
334

Chemistry of Heterocyclic Compounds 2018, 54(3), 334–338
Scheme 2. 2-Substituted 4-azaindoles and indoles 3a–j by one-pot
Cu-free Pd-catalyzed alkynylation–cyclization synthesis
Mass spectra (EI, 70 eV) were obtained on a Finnigan TSQ
7000 apparatus. HRMS were performed on a Bruker maxis
4G apparatus (ESI). Elemental analyses were performed on
an Elementar vario MICRO cube. Melting points were
measured on a Büchi Melting Point B-540 and are un-
corrected. The progress of the reactions was monitored using
TLC on silica gel 60 F254 aluminum sheets supplied by
Merck KGaA (Darmstadt). The spots were visualized with
UV light (254 nm) and aqueous potassium permanganate
solution. Crude products were adsorbed on Celite® 545 for
flash chromatography. Flash chromatographic purification
was performed on a Biotage SP1 Flash Chromatography
Purification system using SNAP 100 g cartridges and silica
gel 60 M (0.040–0.063 mm), supplied by Macherey Nagel
(Düren).
All reactions were performed using Schlenk tubes, septa,
and syringes under nitrogen atmosphere. Reagents were
purchased from ABCR GmbH & Co. KG, Alfa Aesar
GmbH & Co. KG, Fisher Scientific GmbH, Merck KGaA,
Sigma-Aldrich Chemie GmbH, VWR International GmbH
and used without further purification.
Synthesis of 2-substituted 4-azaindoles and indoles 3a–j
via one-pot alkynylation–cyclization (General method).
3-Amino-2-bromopyridine (1a) (87 mg, 0.5 mmol) or
2-bromoaniline (1b) (172 mg, 1.00 mmol), Pd(PPh3)2Cl2
(9.0 mg, 13 mmol or 17.5 mg, 25.0 mmol), and
(1-Ad)2PBn·HBr (12 mg, 25 mmol or 23.6 mg, 50.0 mmol)
were placed into a dry screw-cap Schlenk tube with a
magnetic stirring bar, and the vessel was evacuated. After
flushing the vessel with nitrogen, dry DMSO (1.0 or 1.5 ml),
the corresponding alkyne 2a–j (0.6 mmol or 1.2 mmol),
and DBU (225 mg, 1.50 mmol or 457 mg, 3.00 mmol)
were added. The reaction mixture was stirred at 100°C
under nitrogen for 1 h until the bromide was completely
consumed (monitored by TLC). After cooling to room
temperature, KOt-Bu (253 mg, 2.25 mmol or 281 mg,
2.50 mmol) and DMSO (0.50 or 1.00 ml) were added to the
reaction mixture, and the mixture was stirred at 100°C
under nitrogen for 0.25 h. After cooling to room
temperature, deionized water or brine (20 ml) was added to
the mixture. The aqueous layer was extracted several times
with EtOAc or CH2Cl2. The combined organic phases were
dried over anhydrous Na2SO4 and after filtration, the
solvents were removed under reduced pressure. The residue
was purified by flash chromatography on silica gel to give
the analytically pure products 3a–j.
The structures of all compounds 3a–j were unambiguously
assigned by spectroscopic methods (1H and 13C NMR,
IR spectra) and elemental analyses or HRMS. The yields of
4-azaindoles are higher, presumably due to the acidification
of the amino group in the terminal base-mediated
cyclization. As previously shown for 7-azaindoles, it is
very likely that a broad substitution pattern on both o-bromo-
aniline and 3-amino-2-bromopyridine is tolerated as well.
Methodological studies to expand this approach to
decorated 4-azaindoles and indoles are currently underway.
Aliphatic and (hetero)aromatic terminal alkynes can be
successfully employed as substrates for both 4-azaindole
and indole syntheses in an activation-free Pd-catalyzed
alkynylation–cyclization reaction starting from 3-amino-
2-bromopyridine or o-bromoaniline.
Experimental
2-Phenyl-1H-pyrrolo[3,2-b]pyridine (3a) was synthe-
sized from 3-amino-2-bromopyridine (1a) (87 mg, 0.5 mmol)
and phenylacetylene (2a) (61 mg, 0.6 mmol), eluent for
flash chromatography EtOAc–n-hexane, 3:2. Yield 53 mg
(55%), beige solid, mp 249°C. IR spectrum, ν, cm–1: 3082
(w), 3053 (w), 3011 (w), 2969 (w), 2932 (w), 1603 (w),
1568 (w), 1537 (w), 1481 (w), 1456 (m), 1414 (m), 1362 (m),
1343 (m), 1289 (w), 1275 (m), 1227 (w), 1200 (w), 1173 (w),
1157 (w), 1119 (w), 1096 (w), 1074 (w), 1053 (w), 1030 (w),
988 (w), 924 (m), 910 (w), 833 (w), 810 (w), 785 (m), 766 (s),
IR spectra were recorded on a Shimadzu IRAffinity-1
1
apparatus using ATR technique. H and 13C NMR spectra
were recorded on Bruker AVIII 300 (300 and 75 MHz,
respectively, compounds 3a,d,c,h) or Bruker AVIII 600
spectrometers (600 or 150 MHz, respectively, compounds
3b,c,f,g,i,j) in CDCl3 (compounds 3c,d,e–h,j) or DMSO-d6
(compounds 3a,b,i). 17% CS2 was added to the solution of
compound 3d in CDCl3. Residual solvent peaks (7.26 ppm
for 1H nuclei, 77.16 ppm for 13C nuclei in CDCl3; 2.50 ppm
1
1
for H nuclei, 39.52 ppm for 13C nuclei in DMSO-d6) or
735 (m), 687 (s). H NMR spectrum, δ, ppm (J, Hz): 7.06
TMS were used as internal standards. The type of carbon
nuclei was determined by 135-DEPT NMR spectroscopy.
(1H, s, H-3); 7.10 (1H, dd, J = 8.0, J = 4.6, H-6); 7.37–7.38
(1H, m, H Ph); 7.48–7.50 (2H, m, H Ph); 7.77 (1H, d,
335

Chemistry of Heterocyclic Compounds 2018, 54(3), 334–338
J = 8.0, H-7); 7.92–7.93 (2H, m, H Ph); 8.31–8.32 (1H, m,
J = 17.7, =CH2); 6.68 (1H, s, H-3); 6.79 (1H, dd, J = 17.7,
J = 11.2, CH=); 7.07 (1H, dd, J = 8.1, J = 4.5, H-7); 7.62
(1H, d, J = 8.1, H-6); 8.42 (1H, d, J = 4.5, H-5); 10.32 (1H,
br. s, NH). 13C NMR spectrum, δ, ppm: 102.6 (CH); 115.1
(CH2); 117.3 (CH); 118.4 (CH); 127.6 (CH); 130.4 (C);
140.4 (C); 142.9 (CH); 146.7 (C). Mass spectrum, m/z
(Irel, %): 145 (11), 144 [M]+ (100), 143 (27), 142 (6),
118 (20), 117 [M–C2H3]+ (11), 116 (13), 90 (7), 89 (8).
Found, m/z: 145.0761 [M+H]+. C9H9N2. Calculated, m/z:
145.0760.
H-5); 11.82 (1H, br. s, NH). 13C NMR spectrum, δ, ppm:
99.2 (CH); 116.8 (CH); 118.3 (CH); 125.5 (CH); 128.4
(CH); 129.2 (CH); 130.1 (C); 131.7 (C); 141.1 (C); 142.9
(CH); 146.9 (C). Mass spectrum, m/z (Irel, %): 195 (14),
194 [M]+ (100), 193 (25), 192 (7), 167 (6), 166 (8), 97 (11).
Found, m/z: 195.0920 [M+H]+. C13H11N2. Calculated, m/z:
195.0917.
2-(4-tert-Butylphenyl)-1H-pyrrolo[3,2-b]pyridine (3b)
was synthesized from pyridine 1a (87 mg, 0.5 mmol) and
1-(tert-butyl)-4-ethynylbenzol (2b) (95 mg, 0.6 mmol),
eluent for flash chromatography EtOAc–n-hexane, 3:2.
Yield 106 mg (85%), beige solid, mp 290°C (decomp.).
IR spectrum, ν, cm–1: 3061 (w), 2965 (w), 2901 (w),
2868 (w), 1493 (m), 1443 (w), 1410 (m), 1354 (w), 1275 (m),
1267 (m), 1242 (w), 1059 (w), 928 (w), 835 (m), 777 (s).
1H NMR spectrum, δ, ppm (J, Hz): 1.32 (9H, s, C(CH3)3);
6.98–6.99 (1H, m, H-3); 7.08 (1H, dd, J = 8.1, J = 4.6,
H-7); 7.49–7.52 (2H, m, H Ar); 7.72 (1H, dd, J = 8.1,
J = 1.0, H-6); 7.83–7.86 (2H, m, H Ar); 8.29 (1H, dd,
J = 4.6, J = 1.4, H-5); 11.72 (1H, br. s, NH). 13C NMR
spectrum, δ, ppm: 31.1 (CH3); 34.5 (C); 98.6 (CH); 116.5
(CH); 118.1 (CH); 125.2 (CH); 125.8 (CH); 128.9 (C);
129.9 (C); 141.1 (C); 142.7 (CH); 147.0 (C); 151.0 (C).
Mass spectrum, m/z (Irel, %): 251 (14), 250 [M]+ (65),
234 (5), 220 (10), 219 (9), 207 (17), 206 (11), 194 (6), 117
[M–C10H13]+ (6), 103 (32), 91 (6). Found, m/z: 251.1545
[M+H]+. C17H19N2. Calculated, m/z: 251.1543.
2-Butyl-1H-pyrrolo[3,2-b]pyridine (3c) was synthe-
sized from pyridine 1a (87 mg, 0.5 mmol) and hex-1-yne
(2c) (50 mg, 0.6 mmol), eluent for flash chromatography
EtOAc–n-hexane, 3:2. Yield 64 mg (73%), beige solid,
mp 121°C. IR spectrum, ν, cm–1: 3121 (w), 3026 (w),
2957 (w), 2930 (w), 1566 (w), 1549 (w), 1414 (m), 1358 (w),
1277 (w), 953 (w), 907 (w), 835 (w), 814 (w), 779 (s).
1H NMR spectrum, δ, ppm (J, Hz): 0.94 (3H, t, J = 7.3,
CH3); 1.38–1.45 (2H, m, CH2); 1.69–1.76 (2H, m, CH2);
2.79–2.84 (2H, t, J = 7.7, CH2); 6.45 (1H, s, H-3); 7.04
(1H, dd, J = 8.1, J = 4.8, H-7); 7.60–7.63 (1H, m, H-6);
8.38 (1H, dd, J = 4.8, J = 1.3, H-5); 8.82 (1H, br. s, NH).
13C NMR spectrum, δ, ppm: 13.9 (CH3); 22.5 (CH2); 28.5
(CH2); 31.2 (CH2); 99.8 (CH); 115.7 (CH); 117.8 (CH);
129.4 (C); 142.1 (CH); 145.3 (C); 147.3 (C). Mass
spectrum, m/z (Irel, %): 175 (6), 174 [M]+ (38), 145
[M–C2H5]+ (9), 132 (66), 131 [M–C3H7]+ (100), 104 (7),
77 (5), 39 (6). Found, m/z: 175.1231 [M+H]+. C11H15N2.
Calculated, m/z: 175.1230.
2-(4-Methoxyphenyl)-1H-pyrrolo[3,2-b]pyridine (3e)
was synthesized from pyridine 1a (87 mg, 0.5 mmol) and
1-ethynyl-4-methoxybenzene (2e) (79 mg, 0.6 mmol),
eluent for flash chromatography EtOAc–n-hexane, gradient
from 1:1 to 4:1). Yield 89 mg (81%), gray solid, mp 242°C.
IR spectrum, ν, cm–1: 3069 (w), 3044 (w), 3021 (w),
2978 (w), 2911 (w), 1614 (w), 1566 (w), 1516 (w),
1493 (w), 1449 (w), 1414 (m), 1395 (w), 1343 (m), 1283 (w),
1263 (m), 1209 (w), 1194 (w), 1155 (w), 1115 (w),
1086 (w), 1038 (w), 986 (m), 963 (w), 912 (m), 839 (w),
1
820 (w), 801 (w), 783 (s). H NMR spectrum, δ, ppm
(J, Hz): 3.86 (3H, s, OCH3); 6.90 (1H, s, H-3); 6.98–7.00
(2H, m, H Ar); 7.06–7.08 (1H, m, H-7); 7.65–7.66 (3H, m,
H Ar, H-6); 8.43 (1H, d, J = 3.8, H-5); 8.78 (1H, br. s,
NH). 13C NMR spectrum, δ, ppm: 55.5 (CH3); 99.6 (CH);
114.7 (CH); 116.7 (CH); 117.8 (CH); 124.5 (C); 127.0 (CH);
130.0 (C); 141.8 (C); 143.5 (CH); 147.7 (C); 160.2 (C).
Mass spectrum, m/z (Irel, %): 278 (15), 277 (46), 225 (17),
224 [M]+ (100), 210 (13), 209 [M–CH3]+ (86), 201 (5),
199 (10), 183 (7), 182 (6), 181 (38), 180 (5), 179 (8), 154 (8),
153 (8), 152 (8), 149 (9), 135 (7), 128 (7), 127 (13), 112 (8),
77 (8), 43 (6). Found, m/z: 225.1026 [M+H]+. C14H13N2O.
Calculated, m/z: 225.1022.
2-Phenyl-1H-indole (3f)46 was synthesized from 2-bromo-
aniline (1b) (172 mg, 1.00 mmol) and acetylene 2a
(122 mg, 1.20 mmol), eluent for flash chromatography
EtOAc–n-hexane, 1:20. Yield 106 mg (55%), yellow
solid, mp 187°C. IR spectrum, ν, cm–1: 3443 (w), 3050 (w),
3024 (w), 2969 (w), 2957 (w), 2920 (w), 1595 (w),
1491 (w), 1481 (w), 1456 (w), 1447 (w), 1404 (w), 1368 (w),
1348 (w), 1339 (w), 1298 (w), 1260 (w), 1240 (w), 1231 (w),
1202 (w), 1188 (w), 1163 (w), 1123 (w), 1115 (w), 1074 (w),
1049 (w), 1028 (w), 990 (w), 968 (w), 932 (w), 907 (w),
880 (w), 855 (w), 824 (w), 797 (m), 762 (m), 743 (s),
1
689 (s). H NMR spectrum, δ, ppm (J, Hz): 6.82 (1H, d,
J = 1.3, H-3); 7.09–7.22 (2H, m, H Ph); 7.28–7.45 (4H, m,
H indole, H Ph); 7.61–7.65 (3H, m, H indole, H Ph); 8.30
(1H, br. s, NH). 13C NMR spectrum, δ, ppm: 100.1 (CH);
111.0 (CH); 120.4 (CH); 120.8 (CH); 122.5 (CH); 125.3
(CH); 127.8 (CH); 129.2 (CH); 129.4 (C); 132.5 (C);
136.9 (C); 138.0 (C). Mass spectrum, m/z (Irel, %): 194 (16),
193 [M]+ (100), 192 (18), 191 (6), 166 (6), 165 (27),
164 (5), 97 (8), 96 (5), 90 (5), 89 (7), 97 (8), 96 (5), 90 (5),
89 (7).
2-Ethenyl-1H-pyrrolo[3,2-b]pyridine (3d) was synthe-
sized from pyridine 1a (87 mg, 0.5 mmol), but-3-yn-1-ol
(2d) (43 mg, 0.6 mmol), and KOt-Bu (196 mg, 1.75 mmol,
3.5 equiv), eluent for flash chromatography EtOAc–
n-hexane, gradient from 1:1 to 4:1. Yield 22 mg (31%),
beige solid, mp 176°C. IR spectrum, ν, cm–1: 3127 (w),
3077 (w), 3036 (w), 3011 (w), 2967 (w), 2901 (w), 2874 (w),
1613 (w), 1549 (w), 1493 (m), 1460 (w), 1447 (w), 1437 (w),
1416 (w), 1375 (w), 1358 (w), 1289 (w), 1271 (m), 1246 (m),
1209 (w), 1179 (m), 1109 (w), 1063 (w), 1028 (m), 924 (w),
2-(4-tert-Butylphenyl)-1H-indole (3g) was synthesized
from aniline 1b (172 mg, 1.00 mmol) and acetylene 2b
(189 mg, 1.20 mmol), eluent for flash chromatography
EtOAc–n-hexane, 1:20. Yield 131 mg (53%), gray solid,
mp 190°C. IR spectrum, ν, cm–1: 3431 (w), 3051 (w),
1
912 (w), 831 (m), 824 (m), 775 (s). H NMR spectrum,
δ, ppm (J, Hz): 5.36 (1H, d, J = 11.2, =CH2); 5.82 (1H, d,
336

Chemistry of Heterocyclic Compounds 2018, 54(3), 334–338
3032 (w), 2955 (w), 2901 (w), 2866 (w), 1611 (w), 1497 (w),
209 (16), 208 [M–CH3]+ (97), 181 (8), 180 (53), 179 (11),
178 (13), 153 (8), 152 (24), 151 (9), 127 (6), 112 (11),
95 (6), 77 (6).
1454 (w), 1425 (w), 1393 (w), 1352 (w), 1300 (w), 1269 (w),
1242 (w), 1231 (w), 1202 (w), 1186 (w), 1123 (w), 1111 (w),
1049 (w), 1022 (w), 1013 (w), 1005 (w), 963 (w), 924 (w),
2-Cyclopropyl-1H-indole (3j)48 was synthesized from
aniline 1b (344 mg, 2.00 mmol) and cyclopropylacetylene
(2g) (157 mg, 2.40 mmol), eluent for flash chromatography
n-hexane. Yield 233 mg (74%), yellow solid, mp 57°C.
IR spectrum, ν, cm–1: 3396 (w), 3082 (w), 3046 (w),
3003 (w), 2696 (w), 2913 (w), 1915 (w), 1614 (w), 1580 (w),
1553 (w), 1456 (m), 1414 (w), 1393 (w), 1341 (m), 1308 (m),
1281 (w), 1236 (w), 1204 (w), 1152 (w), 1146 (w), 1094 (w),
1067 (w), 1049 (w), 1023 (m), 1013 (w), 970 (w), 928 (w),
1
887 (w), 835 (m), 789 (m), 739 (s). H NMR spectrum,
δ, ppm (J, Hz): 1.35 (9H, s, C(CH3)3); 6.78 (1H, d, J = 1.3,
H-3); 7.08–7.20 (2H, m, H Ph); 7.37–7.39 (1H, d, J = 7.7,
H indole); 7.43–7.47 (2H, m, H Ph); 7.57–7.63 (3H, m,
H indole); 8.27 (1H, br. s, NH). 13C NMR spectrum,
δ, ppm: 31.4 (CH3); 34.8 (C); 99.6 (CH); 111.0 (CH);
120.3 (CH); 120.7 (CH); 122.2 (CH); 125.0 (CH); 126.1
(CH); 129.5 (C); 129.7 (C); 136.9 (C); 138.1 (C); 151.0 (C).
Mass spectrum, m/z (Irel, %): 250 (14), 249 [M]+ (70),
235 (20), 234 [M–CH3]+ (100), 233 (6), 219 (16), 218 (8),
217 (8), 206 (18), 205 (7), 204 (9), 193 (9), 191 (5),
165 (5), 117 (7), 109 (5), 103 (28), 102 (11), 90 (5), 89 (5).
Found, %: C 86.76; H 7.85; N 5.52. C18H19N. Calculated, %:
C 86.70; H 7.68; N 5.62.
1
899 (w), 878 (m), 783 (w), 774 (m), 745 (s), 737 (s). H NMR
spectrum, δ, ppm (J, Hz): 0.73–0.77 (2H, m, CH2); 0.93–
0.96 (2H, m, CH2); 1.93 (1H, tt, J = 8.4, J = 5.1, CH); 6.14
(1H, m, H-3); 7.05–7.10 (2H, m, H indole); 7.23–7.24 (1H,
m, H indole); 7.48–7.50 (1H, m, H indole); 7.90 (1H, br. s,
NH). 13C NMR spectrum, δ, ppm: 7.4 (CH2); 9.0 (CH);
97.8 (CH); 110.3 (CH); 119.8 (2CH); 121.1 (CH); 128.8
(C); 135.9 (C); 141.8 (C). Mass spectrum, m/z (Irel, %): 158
(11), 157 [M]+ (93), 156 (82), 155 (7), 154 (17), 131 (11),
130 (100), 129 [M–C2H4]+ (30), 128 (30), 127 (10), 117 (5),
115 (6), 103 (7), 102 (6), 89 (6), 78 (5), 77 (12), 65 (5), 63 (5).
2-(Pyridin-2-yl)-1H-indole (3h)47 was synthesized from
aniline 1b (172 mg, 1.00 mmol) and 2-ethynylpyridine (2f)
(121 mg, 1.20 mmol), eluent for flash chromatography
n-hexane. Yield 45 mg (23%), yellow solid, mp 190°C.
IR spectrum, ν, cm–1: 3202 (w), 3071 (w), 3053 (w),
3021 (w), 2974 (w), 2951 (w), 1597 (m), 1532 (w), 1545 (w),
1468 (w), 1443 (w), 1412 (w), 1368 (w), 1341 (w), 1304 (m),
1262 (w), 1227 (w), 1190 (w), 1144 (w), 1071 (w), 1047 (w),
999 (w), 936 (w), 808 (w), 777 (s), 748 (s), 735 (s).
1H NMR spectrum, δ, ppm (J, Hz): 7.05 (1H, s, H-3); 7.13
(1H, td, J = 7.6, J = 2.3, H indole); 7.18 (1H, dd, J = 6.9,
J = 5.3, H indole); 7.22 (1H, t, J = 7.6, H indole); 7.37–
7.38 (1H, m, H indole); 7.68 (1H, dd, J = 7.8, J = 2.7,
H pyridine); 7.72 (1H, td, J = 7.8, J = 1.6, H pyridine); 7.82–
7.83 (1H, m, H pyridine); 8.59–8.60 (1H, m, H pyridine);
10.04 (1H, br. s, NH). 13C NMR spectrum, δ, ppm: 100.8
(CH); 111.6 (CH); 120.1 (CH); 120.2 (CH); 121.3 (CH);
122.1 (CH); 123.3 (CH); 129.2 (C); 136.8 (3C); 149.2 (CH);
150.6 (C). Mass spectrum, m/z (Irel, %): 195 (15), 194 [M]+
(100), 193 (42), 192 (11), 168 (6), 167 (12), 166 (11),
139 (5), 97 (7), 89 (7), 84 (6), 70 (7), 43 (22). Found, %:
C 80.10; H 5.37; N 14.12. C13H10N2. Calculated, %:
C 80.39; H 5.19; N 14.42.
1
Supplementary information file containing H and 13C
NMR spectra and 135-DEPT experiments of synthesized
compounds is available at the journal website at http://
link.springer.com/journal/10593.
The authors cordially thank the Fonds der Chemischen
Industrie for financial support (scholarship for Timo Lessing).
The authors cordially thank the microanalytical
laboratory of the Institut für Medizinische und Pharma-
zeutische Chemie at the Heinrich-Heine-Universität
Düsseldorf for the elemental analyses measurment.
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