3
ꢀFluoroimidazo[1,2ꢀa]pyridines
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 2, February, 2005
471
Experimental
Methyl 3ꢀfluoroꢀ7ꢀmethylimidazo[1,2ꢀа]pyridineꢀ2ꢀcarboxyꢀ
late (3b) was synthesized similarly to compound 3a. The yield
was 77%, m.p. 139—141 °С. Found (%): C, 57.51; H, 4.47;
N, 13.28. C H FN O . Calculated (%): C, 57.69; H, 4.36;
1H and 19F NMR spectra were recorded on a Bruker
DXP 200 spectrometer in CDCl3 (1a—c) and DMSOꢀd6
3a—c, 4) using residual signals from protons of the deuterated
10
9
2
2
1
N, 13.46. H NMR, δ: 2.35 (d, 3 Н, Me, J
3
= 1.0 Hz);
H(Me),H(6)
.86 (s, 3 Н, MeO); 6.84 (dd, 1 Н, H(6), JH(6),H(5) = 7.0 Hz,
JH(6),H(8) = 1.6 Hz); 7.24 (m, 1 Н, H(8)); 8.05 (dd, 1 Н, H(5),
(
1
solvent as reference ( H) and CF COOH as external stanꢀ
3
1
9
dard ( F). Melting points were determined in a glass capillary.
Methyl 3,3,3ꢀtrifluoroꢀ2ꢀ(pyridineꢀ2ꢀimino)propionate (1а).
Methyl trifluoropyruvate (7.8 g, 50 mmol), pyridine (7.8 g,
19
JH(5),H(6) = 7.0 Hz, JH(5),H(8) = 0.6 Hz). F NMR, δ: –66.01 (d,
JF,H(8) = 1.8 Hz).
Methyl 3ꢀfluoroꢀ5ꢀmethylimidazo[1,2ꢀа]pyridineꢀ2ꢀcarboxyꢀ
late (3c) was synthesized similarly to compound 3a. The yield
was 75%, m.p. 128—129 °С. Found (%): C, 57.54; H, 4.55;
N, 13.31. C H FN O . Calculated (%): C, 57.69; H, 4.36;
1
00 mmol), and SOCl (6 g, 50 mmol) were successively added
2
with stirring to a solution of 2ꢀaminopyridine (4.7 g, 50 mmol)
in benzene (50 mL). After the end of the exothermic reaction,
the reaction mixture was stirred for 1 h, the precipitate that
formed was filtered off, and the filtrate was concentrated and
subjected to fractional distillation in vacuo. The yield was 9.1 g
78%), b.p. 89—90 °С (5 Torr). Found (%): C, 46.38; H, 3.21;
N, 12.25. C H FN O . Calculated (%): C, 46.56; H, 3.04;
N, 12.07. H NMR, δ: 3.83 (s, 3 Н, MeO); 7.25 (t, 1 Н, H arom.,
J = 8.0 Hz); 7.37 (d, 1 Н, H arom., J = 8.0 Hz); 7.82 (t, 1 Н,
H arom., J = 8.0 Hz); 8.45 (d, 1 Н, H arom., J = 8.0 Hz).
1
0
9
2
2
1
N, 13.46. H NMR, δ: 2.75 (d, 3 Н, Me, J
= 6.5 Hz); 3.88 (s,
H,F
3
Н, MeO); 6.61 (d, 1 Н, H(6), JH(6),H(7) = 8.0 Hz); 7.11 (t, 1 Н,
H(7), J = 8.0 Hz); 7.28 (dd, 1 Н, H(8), J = 8.0 Hz,
H(8),H(7)
(
19
JH,F = 2.0 Hz). F NMR, δ: –61.98 (dq, JF,H(8) = 2.2 Hz,
9
7
2
2
JF,H(Me) = 6.3 Hz).
1
3
ꢀFluoroꢀ7ꢀmethylimidazo[1,2ꢀа]pyridineꢀ2ꢀcarboxylic acid
(
4). A solution of compound 3b (1.04 g, 5 mmol) in concenꢀ
trated HCl (10 mL) was refluxed for 3 h, cooled, and neutralized
19
F NMR, δ: 7.99 (s).
with 25% NH . The precipitate that formed was filtered off. The
3
Methyl 3,3,3ꢀtrifluoroꢀ2ꢀ(4ꢀmethylpyridineꢀ2ꢀimino)proꢀ
yield was 0.7 g (72%), m.p. 243—245 °С (with decomp.).
pionate (1b) was synthesized similarly to compound 1а. The
yield was 75%, b.p. 93—95 °С (5 Torr). Found (%): C, 48.61;
H, 3.87; N, 11.25. C H FN O . Calculated (%): C, 48.79;
Found (%): C, 55.48; H, 3.47; N, 14.25. C H FN O . Calcuꢀ
9
7
2
2
1
lated (%): C, 55.67; H, 3.63; N, 14.43. H NMR, δ: 2.59 (s, 3 Н,
Me); 7.27 (d, 1 Н, H(6), J = 8.0 Hz); 7.65 (s, 1 Н, H(8)); 8.25
br.s, 1 Н, ОН); 8.62 (d, 1 Н, H(5), J = 8.0 Hz). F NMR, δ:
64.04 (s).
9
7
2
2
1
H, 3.68; N, 11.38. H NMR, δ: 2.40 (s, 3 Н, Me); 3.85 (s, 3 Н,
MeO); 7.22 (dd, 1 Н, H arom., J = 8.0 Hz, J = 5.0 Hz); 7.63 (d,
Н, H arom., J = 8.0 Hz); 8.23 (d, 1 Н, H arom., J = 5.0 Hz).
F NMR, δ: 8.00 (s).
1
9
(
–
1
19
References
Methyl 3,3,3ꢀtrifluoroꢀ2ꢀ(6ꢀmethylpyridineꢀ2ꢀimino)proꢀ
pionate (1с) was synthesized similarly to compound 1а. The
yield was 80%, b.p. 96—97 °С (5 Torr). Found (%): C, 48.63;
H, 3.85; N, 11.21. C H FN O . Calculated (%): C, 48.79;
1
. V. B. Sokolov, A. Yu. Aksinenko, O. V. Korenchenko, and
I. V. Martynov, Izv. Akad. Nauk SSSR, Ser. Khim., 1989,
1213 [Bull. Acad. Sci. USSR, Div. Chem. Sci., 1989, 38, 1106
9
7
2
2
1
H, 3.68; N, 11.38. H NMR, δ: 2.45 (s, 3 Н, Me); 3.85 (s, 3 Н,
MeO); 7.12, 7.21, 7.70 (all d, 1 Н each, H arom., J = 8.0 Hz).
(
Engl. Transl.)].
19
2. O. V. Korenchenko, A. Yu. Aksinenko, V. B. Sokolov, and
F NMR, δ: 8.14 (s).
I. V. Martynov, Heteroatom Chem., 1992, 3, 147.
Methyl 3ꢀfluoroimidazo[1,2ꢀа]pyridineꢀ2ꢀcarboxylate (3а).
Trimethyl phosphite 2 (1.24 g, 10 mmol) was added with stirring
to a solution of 2ꢀpyridylimine 1a (2.3 g, 10 mmol) in DMF
3
4
5
. K. Burger, H. Goth, and E. Daltrozzo, Z. Naturforsch., Teil B,
982, 37, 473.
1
. K. Burger, S. Tremmet, W. D. Roth, and H. Goth,
J. Heterocycl. Chem., 1981, 18, 247.
. O. V. Korenchenko, A. Yu. Aksinenko, A. N. Pushin, V. B.
Sokolov, and I. V. Martynov, Izv. Akad. Nauk SSSR, Ser.
Khim., 1990, 2879 [Bull. Acad. Sci. USSR, Div. Chem. Sci.,
(
20 mL). After the end of the exothermic reaction, the reaction
mixture was stirred for 1 h, Н О (100 mL) was added, and the
2
precipitate that formed was filtered off and recrystallized
from 50% aqueous EtOH. The yield was 1.5 g (77%), m.p.
1
51—153 °С. Found (%): C, 55.48; H, 3.47; N, 14.25.
1
990, 39, 2615 (Engl. Transl.)].
C H FN O . Calculated (%): C, 55.67; H, 3.63; N, 14.43.
9
7
2
2
1
6. K. Burger, E. Hoss, K. Gaa, N. Sewald, and C. Schierlinger,
H NMR, δ: 3.85 (s, 3 Н, MeO); 6.96 (dd, 1 Н, H(6), JH(6),H(5)
=
Z. Naturforsch., Teil B, 1991, 46, 361.
7
7
(
.0 Hz, JH(6),H(7) = 8.0 Hz); 7.21 (t, 1 Н, H(7), J = 8.0 Hz);
.25 (dd, 1 Н, H(8), JH(8),H(7) = 8.0 Hz, J = 2.0 Hz); 8.16
H,F
d, 1 Н, H(5), JH(5),H(6) = 7.0 Hz). 19F NMR, δ: –65.48 (d,
Received September 16, 2004;
JF,H(8) = 2.0 Hz).
in revised form December 1, 2004