Novel 5,6,7,8-tetrahydroimidazo[2′,1′:2,3]thiazolo[5,4-c]pyridine derivatives

Article abstract of DOI:10.1515/hc-2016-0137

Starting with 4-piperidone, new 5,6,7,8-tetrahydroimidazo[2′,1′:2,3]thiazolo [5,4-c]pyridines were synthesized. Structures of these compounds were confirmed by ¹H NMR, ¹³C NMR, MS and elemental analysis.

Full text of DOI:10.1515/hc-2016-0137

Heterocycl. Commun. 2016; 22(5): 291–294
XNixoi Hvoue, lJia5nx,u6e ,Ya7n,g8, L-intlientMraao,hCayoxduarnoLiomu* ainddaLozngofe[i2Ma′,o1′:2,3]
thiazolo[5,4-c]pyridine derivatives
DOI 10.1515/hc-2016-0137
to react with elemental sulfur and cyanamide in the pres-
ence of p-toluenesulfonic acid to form N-Boc-2-amino-
4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (3). Compound 3
was allowed to react with a variety of 3-bromoacetyl-bear-
ing compounds to form cyclic products 4a–k. These com-
pounds were then deprotected to give compounds 5a–k.
The molecular structures of 5a–k were analyzed using
Received July 20, 2016; accepted August 27, 2016
Abstract: Starting with 4-piperidone, new 5,6,7,8-tetrahyd
roimidazo[2′,1′:2,3]thiazolo [5,4-c]pyridines were synthe-
sized. Structures of these compounds were confirmed by
1H NMR, 13C NMR, MS and elemental analysis.
Keywords:
4-piperidone;
5,6,7,8-tetrahydroimi- 1H NMR, 13C NMR, and elemental analysis. The presence of
dazo[2′,1′:2,3]thiazolo [5,4-c]pyridine; synthesis.
water in the reaction mixture leading to 3 greatly reduces
the yield of compound 3. Due to the fact that the catalyst
p-toluenesulfonic acid is a monohydrate and water is also
produced in the course of the reaction, the water must be
constantly removed using a Dean-Stark apparatus. The
yield of compound 3 increases with increasing tempera-
ture up to 90°C. A further increase in temperature lowers
the yield due to formation of by-products. A catalyst is
not required for the subsequent synthesis of 4a. The reac-
tions conducted in solvents of low polarity including 1,4-
dioxane, benzene and toluene furnish higher yields of 4a
(76–82%) compared to the polar solvents such as metha-
nol (34%), ethanol (51%) and acetonitrile (59%). The use
of dichloromethane as a solvent gives product 4a in a low
yield of 23%, which indicates, as already mentioned, that
low temperature is an adverse factor. Overall, 1,4-dioxane
is a preferred solvent when compared with highly toxic
benzene and toluene with high boiling point that makes
it difficult to remove.
Introduction
Piperidine (hexahydropyridine) and imidazole are impor-
tant nitrogen-containing heterocyclic compounds. Piperi-
dine has good water solubility due to its basic group.
The piperidine ring structure is often introduced into
drug molecules, which can improve bioavailability and
efficacy of the drugs [1]. Imidazole is widely present in
natural products, and a variety of its derivatives have been
developed to treat bacterial infection, cancer, inflamma-
tory disease and low blood sugar among other things [2].
There are reports [3, 4] that tetrahydropyridine derivatives
alter the Hedgehog signaling pathway and thus signifi-
cantly inhibit the growth of prostate cancer, pancreatic
cancer, breast cancer and some blood cancers. There are
also reports [5–8] that imidazole compounds inhibit Met
receptor tyrosine kinase, which indicates the potential
therapeutical benefits of such compounds. Several new
compounds containing tetrahydropyridine and imidazole,
4 and 5, were synthesized as part of this work (Scheme 1).
Conclusion
The reported synthesis of 5,6,7,8-tetrahydroimi-
dazo[2′,1′:2,3]thiazolo[5,4-c]pyridines (5a–k) is experi-
mentally simple and highly efficient.
Results and discussion
Theaminogroupof4-piperidone(1)wasfirstprotectedwith
a Boc group to give compound 2 which then was allowed
Experimental
Melting points were determined on a YUHUA X-3 melting point
apparatus and are uncorrected. The 1H NMR (400 MHz) and 13C (100
MHz) spectra were recorded in CDCl3 on a Bruker Avance 400 spec-
trometer. The electrospray ionization mass spectra (ESI-MS) were
recorded on a Bruker Esquire 3000 instrument. Elemental analy-
ses were conducted using an ELTRA analyzer. All reagents were
obtained from commercial sources and used without further purifi-
cation. All reactions were monitored by thin-layer chromatography
*Corresponding author: Caoxuan Lou, Department of Pharmacy, The
First Affiliated Hospital and College of Clinical Medicine of Henan
University of Science and Technology, 471003 Luoyang, Henan,
P. R. China, e-mail: 3240283615@qq.com
Xixi Hou, Jianxue Yang, Linlin Mao and Longfei Mao: Department
of Pharmacy, The First Affiliated Hospital and College of Clinical
Medicine of Henan University of Science and Technology, 471003
Luoyang, Henan, P. R. China
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ꢀX. Hou et al.: 5,6,7,8-Tetrahydroimidazo[2′,1′:2,3]thiazolo[5,4-c]pyridine derivatives
NH2
R
O
N
O
O
1) pyrrolidine, TsOH.H2O
cyclohexane, reflux
(Boc)2O(1.1eq)
TEA(3.0eq)
S
(1.1eq)
N
Br
N
R
2) S8, cyanamide
MeOH, 0oC
N
S
THF rf
N
1,4-dioxane, reflux
N
N
H
Boc
Boc
Boc
4a–k
1
3
2
R
g: R= 4-fluorophenyl
h: R= methyl
i : R= isopropyl
j : R= 4-nitrophenyl
k: R= p-tolyl
a: R= 4-cyanophenyl
b: R= tert-butyl
N
HCl/MeOH
N
c: R= phenyl
d: R= trifluoromethyl
e: R= 4-chlorophenyl
f : R= 3-methoxyphenyl
MeOH, r.t
S
HN
HCl
5a–k
Scheme 1ꢀ
(TLC). Compound 2 was synthesized by using previously published
procedure [9, 10].
7.02 (s, 1 H), 4.49 (s, 2 H), 3.81 (t, Jꢀ=ꢀ5.2 Hz, 2 H), 2.71 (t, Jꢀ=ꢀ5.2 Hz, 2
+
H), 1.48 (s, 9 H), 1.33 (s, 9 H); MS: m/z 335.8, [M+H] . Anal. Calcd for
C17H25N3O2S: C, 60.87; H, 7.51; N, 12.53. Found: C, 60.79; H, 7.54; N, 12.55.
tert-Butyl 2-phenyl-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]thiazolo-
Synthesis of tert-butyl 2-amino-4,5,6,7-
1
[5,4-c]pyridine-7-carboxylate (4c)ꢁYield 72%; H NMR: δ 7.94 (s, 1
tetrahydrothiazolo[5,4-c]pyridine-5-carboxylate (3)
H), 7.79 (d, Jꢀ=ꢀ7.6 Hz, 2 H), 7.40 (t, Jꢀ=ꢀ7.2 Hz, 2 H), 7.30 (t, Jꢀ=ꢀ7.2 Hz, 1 H),
4.58 (s, 2 H), 3.87 (t, Jꢀ=ꢀ6.0 Hz, 2 H), 2.85–2.82 (m, 2 H), 1.54 (s, 9 H);
+
To a solution of compound 2 (30 g, 150 mmol) in cyclohexane (100
mL) were added pyrrolidine (13.2 mL, 158 mmol) and TsOH·H2O (1.43
g, 7.53 mmol) and the mixture was heated under reflux for 3 h with
constant removal of water using a Dean-Stark apparatus. After cool-
ing to room temperature, the mixture was filtered and the filtrate was
concentrated. The residue was dissolved in dry methanol (130 mL),
and the solution was treated with elemental sulfur (S8, 4.8 g, 151
mmol) followed by addition of a solution of cyanamide (6.34 g, 151
mmol) in dry methanol (20 mL) dropwise at 0°C. The mixture was
stirred for 2 h at 90°C. After concentration, the residue was purified
by column chromatography on silica gel eluting with petroleum
ether/ethyl acetate, 1:2, to give 22.8 g (59%) of compound 3 as a
pale yellow solid; 1H NMR: δ 4.26 (s, 2 H), 3.56 (t, Jꢀ=ꢀ5.7 Hz, 2 H), 2.42
MS: m/z 356.2, [M+H] . Anal. Calcd for C19H21N3O2S: C, 64.20; H, 5.95;
N, 11.82. Found: C, 64.27; H, 5.94; N, 11.76.
tert-Butyl2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]
thiazolo[5,4-c]pyridine-7-carboxylate (4d)ꢁYield 70%; 1H NMR: δ
7.63 (s, 1 H), 4.56 (s, 2 H), 3.86 (t, Jꢀ=ꢀ5.6 Hz, 2 H), 2.79 (m, 2 H), 1.48 (s,
+
9 H); MS: m/z 347.8, [M+H] . Anal. Calcd for C14H16F3N3O2S: C, 48.41; H,
4.64; N, 12.10. Found: C, 48.45; H, 4.65; N, 12.17.
tert-Butyl2-(4-chlorophenyl)-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]
1
thiazolo[5,4-c]pyridine-7-carboxylate (4e)ꢁYield 61%; H NMR: δ
7.74 (d, Jꢀ=ꢀ8.4 Hz, 2 H), 7.56 (s, 1 H), 7.35 (d, Jꢀ=ꢀ8.4 Hz, 2 H), 4.53 (m, 2
+
H), 3.86 (m, 2 H), 2.77 (m, 2 H), 1.49 (s, 9 H); MS: m/z 390.1, [M+H] .
+
(m, 2 H), 1.36 (s, 9 H); MS: m/z 256.3, [M+H] .
Anal. Calcd for C19H20ClN3O2S: C, 58.53; H, 5.17; N, 10.78. Found: C,
58.51; H, 5.14; N, 10.72.
General procedure for the preparation of 4a–k
tert-Butyl 2-(3-methoxyphenyl)-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]
1
thiazolo[5,4-c]pyridine-7-carboxylate (4f)ꢁYield 67%; H NMR: δ
7.57 (s, 1 H), 7.42 (s, 1 H), 7.33 (d, Jꢀ=ꢀ7.6 Hz, 1 H), 7.27 (t, Jꢀ=ꢀ8.0 Hz, 1 H),
6.83 (d, Jꢀ=ꢀ8.0 Hz, 1 H), 4.54 (m, 2 H), 3.81 (m, 5 H), 2.77 (m, 2 H), 1.50
To a solution of compound 3 (50.3 g, 197 mmol) in 1,4-dioxane (1000
mL) was added R-C(O)CH2Br (217 mmol, see Scheme 1 for R) in one
portion. After stirring at room temperature for 1 h, the mixture was
heated under reflux overnight. After concentration, the residue was
purified by column chromatography on silica gel eluting with petro-
leum ether/ethyl acetate, 2:1, to give compound 4a–k as a pale yellow
solid; yield 80%.
+
(s, 9 H); MS: m/z 386.2, [M+H] . Anal. Calcd for C20H23N3O3S: C, 62.32;
H, 6.01; N, 10.90. Found: C, 62.30; H, 6.05; N, 10.87.
tert-Butyl 2-(4-fluorophenyl)-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]
thiazolo[5,4-c]pyridine-7-carboxylate (4g)ꢁYield 64%; 1H NMR: δ
7.68 (d, Jꢀ=ꢀ8.4 Hz, 2 H), 7.55 (s, 1 H), 7.39 (d, Jꢀ=ꢀ8.4 Hz, 2 H), 4.41 (m,
+
2 H), 3.87 (m, 2 H), 2.74 (m, 2 H), 1.47 (s, 9 H); MS: m/z 374.5, [M+H] .
tert-Butyl 2-(4-cyanophenyl)-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]
thiazolo[5,4-c]pyridine-7-carboxylate (4a)ꢁYield 80%; 1H NMR: δ
7.89 (d, Jꢀ=ꢀ8.8 Hz, 2 H), 7.65 (m, 2 H), 7.37 (s, 1 H), 4.54 (s, 2 H), 3.86 (t,
Anal. Calcd for C19H20FN3O2S: C, 61.11; H, 5.40; N, 11.25. Found: C, 61.17;
H, 5.45; N, 11.21.
+
Jꢀ=ꢀ5.6 Hz, 2 H), 2.79–2.76 (m, 2 H), 1.49 (s, 9 H); MS: m/z 380.9, [M+H] .
Anal. Calcd for C20H20N4OS: C, 63.14; H, 5.30; N, 14.73. Found: C, 63.17;
H, 5.34; N, 14.75.
tert-Butyl 2-methyl-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]thiazolo-
[5,4-c]pyridine-7-carboxylate (4h)ꢁYield 76%; 1H NMR: δ 7.79 (s, 1
H), 4.71 (s, 2 H), 3.69 (t, Jꢀ=ꢀ5.6 Hz, 2 H), 2.87 (m, 2 H), 2.36 (s, 3 H), 1.45
+
tert-Butyl 2-(tert-butyl)-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]thia-
zolo[5,4-c]pyridine-7-carboxylate (4b)ꢁYield 75%; 1H NMR: δ
(s, 9 H); MS: m/z 294.4, [M+H] . Anal. Calcd for C14H19N3O2S: C, 57.31;
H, 6.53; N, 14.32. Found: C, 57.36; H, 6.61; N, 14.33.
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X. Hou et al.: 5,6,7,8-Tetrahydroimidazo[2′,1′:2,3]thiazolo[5,4-c]pyridine derivativesꢂ
ꢂ293
for C9H9ClF3N3S: C, 38.10; H, 3.20; N, 14.81. Found: C, 38.16; H, 3.14;
N, 14.85.
tert-Butyl 2-isopropyl-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]thia-
1
zolo[5,4-c]pyridine-7-carboxylate (4i)ꢁYield 73%; H NMR: δ 7.56
(s, 1 H), 4.93 (s, 2 H), 3.66 (t, Jꢀ=ꢀ5.6 Hz, 2 H), 3.17 (d, Jꢀ=ꢀ8.0 Hz, 1 H),
+
2-(4-Chlorophenyl)-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]
thiazolo[5,4-c]pyridine hydrochloride (5e)ꢁYellow solid; yield
94%; mp 271–274°C; 1H NMR: δ 10.16 (s, 1 H), 8.51 (s, 1 H), 7.87 (d, Jꢀ=ꢀ8.8
Hz, 2 H), 7.52 (d, Jꢀ=ꢀ8.8 Hz, 2 H), 4.32 (m, 2 H), 3.54 (m, 2 H), 3.11 (m, 2
H); 13C NMR: δ 165.2, 153.3, 139.3, 138.6, 131.8, 129.3, 124.7, 104.1, 59.8,
2.60 (m, 2 H), 1.65 (s, 9 H), 1.38 (s, 6 H); MS: m/z 322.5, [M+H] . Anal.
Calcd for C16H23N3O2S: C, 59.78; H, 7.21; N, 13.07. Found: C, 59.76; H,
7.19; N, 13.03.
tert-Butyl 2-(4-nitrophenyl)-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]
+
1
56.3, 47.3, 41.9; MS: m/z 289.7, [M+H] . Anal. Calcd for C14H13Cl2N3S: C,
thiazolo[5,4-c]pyridine-7-carboxylate (4j)ꢁYield 59%; H NMR: δ
51.54; H, 4.02; N, 12.88. Found: C, 51.49; H, 4.04; N, 12.85.
7.97 (d, Jꢀ=ꢀ8.4 Hz, 2 H), 7.65 (s, 1 H), 7.48 (d, Jꢀ=ꢀ8.4 Hz, 2 H), 4.93 (m, 2
H), 3.76 (d, Jꢀ=ꢀ8.4 Hz, 2 H), 2.83 (m, 2 H), 1.43 (s, 9 H); MS: m/z 401.4,
+
2-(3-Methoxyphenyl)-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]
thiazolo[5,4-c]pyridine hydrochloride (5f)ꢁYellow solid; yield
[M+H] . Anal. Calcd for C19H20N4O4S: C, 56.99; H, 5.03; N, 13.99. Found:
C, 56.96; H, 5.01; N, 13.93.
1
96%; mp 174–177°C; H NMR: δ 10.13 (s, 1 H), 8.58 (s, 1 H), 7.44 (m, 2
H), 7.36 (t, Jꢀ=ꢀ8.0 Hz, 1 H), 6.91 (d, Jꢀ=ꢀ8.0 Hz, 1 H), 4.33 (m, 2 H), 3.81
(s, 3 H), 3.54 (m, 2 H), 3.10 (m, 2 H); 13C NMR: δ 165.3, 152.9, 139.4,
138.6, 131.8, 127.9, 122.2, 107.1, 101.5, 59.8, 52.9, 44.2, 39.5; MS: m/z
tert-Butyl
2-(p-tolyl)-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]thia-
1
zolo[5,4-c]pyridine-7-carboxylate (4k)ꢁYield 54%; H NMR: δ 7.76
(d, Jꢀ=ꢀ8.4 Hz, 2 H), 7.67 (s, 1 H), 7.39 (d, Jꢀ=ꢀ8.4 Hz, 2 H), 4.81 (m, 2 H),
3.65 (d, Jꢀ=ꢀ8.4 Hz, 2 H), 2.75 (m, 2 H), 2.17 (s, 3 H), 1.43 (s, 9 H); MS: m/z
+
286.3, [M+H] . Anal. Calcd for C15H16ClN3OS: C, 55.98; H, 5.01; N, 13.06.
+
Found: C, 55.92; H, 5.04; N, 13.05.
370.5, [M+H] . Anal. Calcd for C20H23N3O2S: C, 65.01; H, 6.27; N, 11.37.
Found: C, 65.06; H, 6.32; N, 11.33.
2-(4-Fluorophenyl)-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]
thiazolo[5,4-c]pyridine hydrochloride (5g)ꢁYellow solid; yield
1
89%; mp 217–219°C; H NMR: δ 10.21 (s, 1 H), 8.57 (s, 1 H), 7.69 (d,
General procedure for the preparation of 5a–k
Jꢀ=ꢀ8.8 Hz, 2 H), 7.46 (d, Jꢀ=ꢀ8.8 Hz, 2 H), 4.27 (m, 2 H), 3.53 (m, 2 H),
3.08 (m, 2 H); 13C NMR: δ 164.7, 154.1, 139.3, 138.7, 132.2, 129.6, 124.5,
To a solution of compound 4a–k (84.5 mmol) in methanol (350 mL)
was added dropwise a solution of 4 m HCl in MeOH (300 mL) at 0°C.
The mixture was stirred at room temperature for 0.5 h and then con-
centrated to afford compound 5a–k.
+
104.3, 59.8, 56.3, 47.5, 42.3; MS: m/z 274.4, [M+H] . Anal. Calcd for
C14H13ClFN3S: C, 54.28; H, 4.23; N, 13.56. Found: C, 54.19; H, 4.34;
N, 13.55.
2-Methyl-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]thiazolo[5,4-c]pyri-
dine hydrochloride (5h)ꢁWhite solid; yield 97%; mp 167–169°C; 1H
NMR: δ 10.17 (s, 1 H), 7.97 (s, 1 H), 4.11 (s, 2 H), 3.62 (t, Jꢀ=ꢀ6.0 Hz, 2 H),
2.83 (d, Jꢀ=ꢀ6.0 Hz, 2 H), 2.21 (s, 3 H); 13C NMR: δ 159.6, 131.4, 130.1,
4-{(5,6,7,8-Tetrahydroimidazo[2′,1′:2,3]thiazolo[5,4-c]pyridine-
2-yl}benzonitrile hydrochloride (5a)ꢁYellow solid; yield 98%;
1
mp 199–201°C; H NMR: δ 10.26 (s, 1 H), 8.52 (s, 1 H), 8.00 (d, Jꢀ=ꢀ8.4
+
Hz, 2 H), 7.86 (d, Jꢀ=ꢀ8.4 Hz, 2 H), 4.52 (s, 2 H), 3.78 (t, Jꢀ=ꢀ6.0 Hz, 2 H),
117.6, 98.9, 59.3, 53.2, 44.6, 21.7; MS: m/z 248.2, [M+H] . Anal. Calcd for
3.28 (m, 2 H); 13C NMR: δ 165.2, 153.1, 139.4, 138.6, 131.8, 127.9, 122.2,
C9H12ClN3S: C, 47.05; H, 5.27; N, 18.29. Found: C, 46.97; H, 5.34; N, 18.17.
+
107.1, 101.5, 59.8, 56.3, 47.3, 42.1; MS: m/z 281.2, [M+H] . Anal. Calcd
for C15H13ClN4S: C, 56.87; H, 4.14; N, 17.68. Found: C, 56.89; H, 4.09;
N, 17.65.
2-Isopropyl-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]thiazolo[5,4-c]
pyridine hydrochloride (5i)ꢁWhite solid; yield 94%; mp 203–
205°C; 1H NMR: δ 10.11 (s, 1 H), 8.37 (s, 1 H), 4.33 (s, 2 H), 3.59 (t, Jꢀ=ꢀ5.6
Hz, 2 H), 3.21 (d, Jꢀ=ꢀ8.0 Hz, 1 H), 2.45 (m, 2 H), 1.25 (s, 6 H); 13C NMR:
δ 160.4, 132.7, 128.9, 116.3, 100.6, 61.1, 54.8, 45.6, 32.6, 22.9; MS: m/z
2-(tert-Butyl)-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]thiazolo[5,4-c]
pyridine hydrochloride (5b)ꢁYellow solid, yield 98%; mp 142–
144°C; 1H NMR: δ 10.14 (s, 1 H), 8.12 (s, 1 H), 4.67 (s, 2 H), 3.88 (t, Jꢀ=ꢀ6.0
Hz, 2 H), 3.41 (t, Jꢀ=ꢀ6.0 Hz, 2 H), 1.58 (s, 9 H); 13C NMR: δ 159.2, 131.4,
+
222.3, [M+H] . Anal. Calcd for C11H16ClN3S: C, 51.25; H, 6.26; N, 16.30.
Found: C, 51.31; H, 6.23; N, 16.37.
+
126.5, 122.3, 101.8, 59.1, 51.5, 42.3, 28.1, 23.6; MS: m/z 236.1, [M+H] .
Anal. Calcd for C12H18ClN3S: C, 53.03; H, 6.77; N, 15.46. Found: C, 53.09;
H, 6.74; N, 15.49.
2-(4-Nitrophenyl)-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]
thiazolo[5,4-c]pyridine hydrochloride (5j)ꢁYellow solid; yield
87%; mp 241–243°C; 1H NMR: δ 10.37 (s, 1 H), 8.49 (s, 1 H), 8.17 (d, Jꢀ=ꢀ8.8
Hz, 2 H), 7.97 (d, Jꢀ=ꢀ8.8 Hz, 2 H), 4.32 (m, 2 H), 3.36 (m, 2 H), 2.93 (m,
2 H); 13C NMR: δ 165.9, 156.4, 136.7, 131.5, 129.6, 127.7, 121.5, 102.6, 62.3,
2-Phenyl-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]thiazolo[5,4-c]pyri-
dine hydrochloride (5c)ꢁWhite solid; yield 95%; mp 207–209°C; 1H
NMR: δ 10.23 (s, 1 H), 8.19 (s, 1 H), 7.69 (m, 2 H), 7.54 (m, 3 H), 4.56 (s,
2 H), 3.76 (t, Jꢀ=ꢀ5.6 Hz, 2 H), 3.25 (t, Jꢀ=ꢀ6.0 Hz, 2 H); 13C NMR: δ 165.2,
153.3, 139.3, 138.6, 131.8, 127.9, 122.1, 101.5, 59.8, 56.3, 47.3, 41.9; MS:
+
55.4, 42.8, 41.3; MS: m/z 301.4, [M+H] . Anal. Calcd for C14H13ClN4O2S: C,
49.93; H, 3.89; N, 16.64. Found: C, 49.99; H, 3.84; N, 16.65.
+
2-(p-Tolyl)-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]thiazolo[5,4-c]
pyridine hydrochloride (5k)ꢁWhite solid; yield 92%; mp 252–
254°C; 1H NMR: δ 10.25 (s, 1 H), 8.81 (s, 1 H), 7.84 (d, Jꢀ=ꢀ8.8 Hz, 2 H),
7.47 (d, Jꢀ=ꢀ8.8 Hz, 2 H), 4.60 (m, 2 H), 3.32 (d, Jꢀ=ꢀ8.0 Hz, 2 H), 2.74 (m,
2 H), 2.21 (s, 3 H); 13C NMR: δ 160.3, 155.8, 136.7, 129.4, 127.6, 124.9,
m/z 256.3, [M+H] . Anal. Calcd for C14H14ClN3S: C, 57.63; H, 4.84; N,
14.40. Found: C, 57.57; H, 4.89; N, 14.45.
2-(Trifluoromethyl)-5,6,7,8-tetrahydroimidazo[2′,1′:2,3]
thiazolo[5,4-c]pyridine hydrochloride (5d)ꢁWhite solid; yield
+
1
118.1, 101.7, 65.3, 54.5, 42.2, 42.5, 27.6; MS: m/z 270.4, [M+H] . Anal.
91%; mp 191–193°C; H NMR: δ 10.12 (s, 1 H), 8.16 (s, 1 H), 3.95 (s, 2
H), 3.25 (t, Jꢀ=ꢀ6.0 Hz, 2 H), 2.81 (m, 2 H); 13C NMR: δ 161.4, 129.5, 122.5,
Calcd for C15H16ClN3S: C, 58.91; H, 5.27; N, 13.74. Found: C, 58.97; H,
5.24; N, 13.69.
+
119.7, 101.4, 59.7, 52.1, 42.3, 27.3; MS: m/z 248.2, [M+H] . Anal. Calcd
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ꢀꢀꢀꢁ
294ꢀ ꢀX. Hou et al.: 5,6,7,8-Tetrahydroimidazo[2′,1′:2,3]thiazolo[5,4-c]pyridine derivatives
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