686
Y. Liu, W. Zhang, and L. M. Sayre
Vol 47
(þ); HRMS calcd for C7H7N3S (Mþ) 165.0361, found
165.0363.
2H), 4.22 (t, J ¼ 7.6 Hz, 2H), 6.77 (dd, J ¼ 7.7, 6.5 Hz, 1H),
7.13 (d, J ¼ 7.7 Hz, 1H), 7.37 (d, J ¼ 6.5 Hz, 1H); 13C-NMR
(CD3OD) d 14.1 (ꢀ), 20.5 (þ), 30.8 (þ), 55.4 (þ), 115.3 (ꢀ),
120.9 (ꢀ), 128.8 (ꢀ), 135.8 (þ), 146.4 (þ); HRMS calcd for
C9H15N3 (Mþ) 165.1266, found 165.1265.
Preparation of 9 from 11. A solution of 11 (165.2 mg, 1.0
mmol) and CS2 (5 mL) in EtOH (8 mL) in a sealed Teflon-
screwed high-pressure vessel was stirred at 80ꢁC for 24 h and
concentrated. The residue was mixed with MeI (1.41 g, 10.0
mmol) in MeOH (6 mL), stirred at room temperature for 24 h,
and concentrated resulting in a crude mixture, which was sub-
jected to chromatography (EtOAc/MeOH, 4:1) to afford 9
(179.3 mg, 81%). 1H-NMR, 13C-NMR, and HRMS data were
identical with those of 9 prepared from 8.
4-Butyl-2-(methylthio)-4H-imidazo[4,5-b]pyridine (9). A
suspension of 8 (1.65 g, 10.0 mmol) in a solution of n-butyl
iodide (2.76 g, 15.0 mmol) and triethylamine (1.52 g, 15.0
mmol) in benzene (150 mL) was sealed in a Teflon-screwed
high-pressure vessel and stirred at 100ꢁC for 24 h and concen-
trated. The residue was diluted with mixed solvent of CH2Cl2/
MeOH (9:1), basified with 28% aqueous NH4OH solution,
and subjected to chromatography (EtOAc/acetone/MeOH/
1
28%NH4OH, 140:60:10:1) to afford 9 (2.03 g, 92%): H-NMR
(CDCl3) d 0.97 (t, J ¼ 7.3 Hz, 3H), 1.38 (m, 2H), 2.01 (m,
2H), 2.78 (s, 3H), 4.60 (t, J ¼ 7.3 Hz, 2H), 7.07 (dd, J ¼ 7.7,
6.7 Hz, 1H), 7.45 (d, J ¼ 6.6 Hz, 1H), 7.84 (d, J ¼ 7.7 Hz,
1H); 13C-NMR (CDCl3) d 13.6 (ꢀ), 14.6 (ꢀ), 19.8 (þ), 31.6
(þ), 53.9 (þ), 113.5 (ꢀ), 124.0 (ꢀ), 129.2 (ꢀ), 143.2 (þ),
151.8 (þ), 172.1 (þ); HRMS calcd for C11H15N3S (Mþ)
221.0987, found 221.0982.
Preparation of 6 from 9. Chlorine was introduced into a
solution of 9 (664.0 mg, 3.0 mmol) in hydrochloric acid (12N,
300 mL) with stirring at room temperature for 8 h. After
standing overnight, the reaction mixture was concentrated
under reduced pressure. The resulting residue was diluted with
ice water (400 mL), basified with 2N aqueous solution of
NaOH, and extracted with CH2Cl2 (3 ꢂ 100 mL). The com-
bined organic extracts were washed with brine, dried over
Na2SO4, and concentrated resulting in a crude, which was sub-
jected to chromatography (CH2Cl2/CH3OH, 5:1) to afford 6
(597.5 mg, 95%). 1H-NMR, 13C-NMR, and HRMS data were
identical with those of 6 prepared from 5.
Acknowledgments. The authors thank the National Institutes of
Health for support of this work through grants HL 53315 and AG
14249. Case Western Reserve University is acknowledged for
supporting an alumina research fellowship for Y.L. (1998). They
also thank Dr. D. R. Sell and Professor V. M. Monnier for helpful
discussions.
REFERENCES AND NOTES
[1] Current address: Genomics Institute of the Novartis
Research Foundation, San Diego, CA 92121.
[2] Current address: Discovery Chemistry, Hutchison Medi-
Pharma Limited, Shanghai, China 201203.
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4-Butyl-2-(propylamino)-4H-imidazo[4,5-b]pyridine (2). A
mixture of 6 (524.2 mg, 2.50 mmol) and propylamine (1.18 g,
20.0 mmol) in EtOH (30 mL) was sealed in a Teflon-screwed
high-pressure vessel and stirred at 125ꢁC for 24 h and was
evaporated to result in a residue, which was subjected to chro-
matography (CH2Cl2/MeOH, 5:1) to afford 2 (557.2 mg,
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1
96%). H-NMR (CD3OD) d 0.98 (t, J ¼ 7.5 Hz, 3H), 1.01 (t,
J ¼ 7.3 Hz, 3H), 1.38 (m, 2H), 1.72 (m, 2H), 1.96 (m, 2H),
3.46 (t, J ¼ 6.9, 2H), 4.56 (t, J ¼ 7.3, 2H), 7.16 (dd, J ¼ 7.6,
6.6 Hz, 1H), 7.75 (d, J ¼ 7.6 Hz, 1H), 8.00 (d, J ¼ 6.6, 1H);
13C-NMR (CDCl3) d 11.5 (ꢀ), 13.6 (ꢀ), 19.6 (þ), 22.8 (þ),
31.4 (þ), 44.9 (þ), 53.3 (þ), 114.2 (ꢀ), 118.1 (ꢀ), 129.9 (ꢀ),
152.6 (þ), 156.7 (þ), 161.8 (þ); HRMS calcd for C13H20N4
(Mþ) 232.1688, found 232.1685.
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Oda, O.; Ogawa, H. Tetrahedron Lett 1999, 40, 2569; (b) Yokakawa,
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[9] For some examples: (a) Jarvest, R. L.; Armstrong, S. A.;
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2-Amino-3-(butylamino)pyridine (10) and 1-butyl-3-
amino-2-pyridone imine (11). A mixture of 4 (1.09 g, 10.0
mmol) and n-butyl iodide (7.36 g, 40.0 mmol) in EtOH (60
mL) was sealed in a Teflon-screwed high-pressure vessel and
stirred at 95ꢁC for 24 h and concentrated. The resulting resi-
due was dissolved in a mixed solvent of MeOH and water
(1:1) (160 mL), adjusted to pH 10 with 2N aqueous solution
of NaOH, and evaporated ending in a crude, which was sub-
jected to chromatographic (EtOAc/MeOH, 4:1) separation to
afford 10 (1.19 g, 72%) and 11 (396.6 mg, 24%). 10: 1H-
NMR (CDCl3) d 0.97 (t, J ¼ 7.2 Hz, 3H), 1.45 (m, 2H), 1.64
(m, 2H), 3.08 (t, J ¼ 6.7 Hz, 2H), 6.70 (dd, J ¼ 7.6, 4.8 Hz,
1H), 6.80 (d, J ¼ 7.6 Hz, 1H), 7.57 (d, J ¼ 4.8 Hz, 1H); 13C-
NMR (CDCl3) d 14.0 (ꢀ), 20.4 (þ), 31.5 (þ), 43.6 (þ), 115.8
(ꢀ), 116.7 (ꢀ), 132.5 (þ), 135.8 (ꢀ), 148.7 (þ); HRMS calcd
for C9H15N3 (Mþ) 165.1266, found 165.1264. 11: 1H-NMR
(CD3OD) d 0.98 (t, J ¼ 7.3 Hz, 3H), 1.42 (m, 2H), 1.79 (m,
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1175.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet