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DOI: 10.1055/s-0028-1088149
A General and Efficient Synthesis of 2-Substituted Oxazolopyridines
Publication History
Publication Date:
20 March 2009 (online)
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Abstract
Starting from commercially available halonitropyridines and haloaminopyridines, 2-substituted-oxazolo[5,4-b]pyridines, and 2-aryl-oxazolo[4,5-b]pyridines were synthesized in good yields by using a Cu(I)-mediated cyclization of halopyridylamides as a key step.
Key words
copper-catalyzed cyclization - synthesis - heterocycles - oxazolo[5,4-b]pyridines - oxazolo[4,5-b]pyridines
- Supporting Information for this article is available online:
- Supporting Information
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References and Notes
Typical Procedure
for the Synthesis and Purification of 3a
To a mixture
of 2a (2.0 mmol), CuI (0.1 mmol), N,N′-dimethylethylenediamine
(0.2 mmol), and K2CO3 (4.0 mmol) was added
dry toluene (5.0 mL) under a nitrogen atmosphere. The reaction was
refluxed for 12 h and then allowed to cool to r.t. The crude mixture
was added to 10 mL H2O and then was extracted by CH2Cl2 (2 × 20
mL). The organic layer was dried over anhyd Na2SO4 and concentrated
in vacuo to give the crude product, which was further purified by
flash chromatography over silica gel column with PE-EtOAc
(5:1) to give the pure product 3a.
Selected Spectral
Data
Compound 3a: mp 101-102 ˚C. R
f
= 0.55
(EtOAc-PE, 1:2). IR (KBr): 2913, 1617, 1544 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 8.38
(dd, J = 5.1,
1.5 Hz, 1 H), 8.34 (d, J = 1.5 Hz,
1 H), 8.34 (d, J = 2.1
Hz, 1 H), 8.10 (dd, J = 7.8,
1.5 Hz, 1 H), 7.55-7.62 (m, 3 H), 7.36-7.41 (m,
1 H). MS (EI):
m/z = 196 [M]+.
Anal. Calcd for C12H8N2O: C, 73.46;
H, 4.11; N, 14.28. Found: C, 73.46; H, 4.43; N, 14.18.
Compound 3i: mp 79-81 ˚C. R
f
= 0.38
(EtOAc-PE, 1:2). IR (KBr): 2924, 1602, 1523 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 8.35
(dd, J = 4.2,
1.5 Hz, 1 H), 8.21 (dd, J = 7.8,
1.5 Hz, 1 H), 8.12 (dd, J = 7.8,
1.5 Hz, 1 H), 7.53-7.56 (m, 1 H), 7.32-7.37 (m,
1 H), 7.10-7.16 (m, 2 H), 4.05 (s, 3 H). MS (EI): m/z = 226 [M]+.
Anal. Calcd for C13H10N2O2:
C, 69.02; H, 4.46; N, 12.38. Found: C, 68.67; H, 4.34; N, 12.38.
Compound 3k: mp 172-174 ˚C. R
f
= 0.42
(EtOAc-PE, 1:2). IR (KBr): 1496, 1620, 1223 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 8.34
(dd, J = 4.5,
1.5 Hz, 1 H), 8.05 (dd, J = 7.8, 1.5
Hz, 1 H), 7.54 (s, 2 H), 7.33-7.37 (m, 1 H), 4.04 (s, 9
H). MS (EI): m/z = 286 [M]+.
Anal. Calcd for C15H14N2O4:
C, 62.93; H, 4.93; N, 9.79; Found: C, 63.12; H, 4.74; N, 9.78.
Compound 6a: mp 163-164 ˚C. R
f
= 0.38
(EtOAc-PE, 1:2). IR (KBr): 2920, 1670, 1580 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 8.56
(s, 1 H), 8.46 (dd, J = 1.5,
7.2 Hz, 2 H), 7.81 (s, 1 H), 7.75-7.65 (m, 3 H), 2.65 (s,
3 H). ¹³C NMR (75 MHz, CDCl3): δ = 165.1,
154.4, 147.3, 132.3, 130.6, 129.0, 128.0, 126.7, 118.5, 18.9. ESI-MS: m/z = 211 [M+ + 1]. Anal.
Calcd for C13H10N2O: C, 74.27;
H, 4.79; N, 13.33. Found: C, 74.05; H, 4.77; N, 13.28.
Compound 6b: mp 165-167 ˚C. R
f
= 0.35
(EtOAc-PE, 1:2). IR (KBr): 2918, 1620, 1550 cm-¹.¹H
NMR (300 MHz, CDCl3): δ = 8.57
(s, 1 H), 8.32 (d, J = 8.4
Hz, 2 H), 8.01 (d, J = 8.3
Hz, 2 H), 7.84 (s, 1 H), 3.95 (s, 1 H), 2.64 (s, 3 H). ESI-MS: m/z = 241 [M+ + 1].
Anal. Calcd for C13H10N2O: C, 69.99;
H, 5.03; N, 11.66. Found: C, 69.78; H, 4.98; N, 11.69.
Compound 6c: mp 193-194 ˚C. R
f
= 0.32
(EtOAc-PE, 1:2). IR (KBr): 2918, 1610, 1560 cm-¹.¹H
NMR (300 MHz, CDCl3): δ = 8.59
(s, 1 H), 8.16 (d, J = 8.7
Hz, 2 H), 8.04 (d, J = 8.1
Hz, 2 H), 7.84 (s, 1 H), 2.64 (s, 3 H). ¹³C
NMR (75 Hz, CDCl3): δ = 164.3,
154.2, 147.7, 143.3, 138.4, 130.9, 129.3, 126.2, 118.6, 99.5, 18.9.
ESI-MS: m/z = 337 [M+ + 1]. Anal.
Calcd for C13H9IN2O: C, 46.45;
H, 2.70, N, 8.33. Found: C, 46.53; H, 2.75; N, 8.40.