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DOI: 10.1055/s-0031-1290075
Four-Component Synthesis of Indazole through Ugi-Azide Coupling
Publikationsverlauf
Publikationsdatum:
03. Januar 2012 (online)
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Abstract
ortho-Nitrobenzaldehyde and trimethylsilyl azide were used in a Ugi-Cadogan cascade towards tetrazolyl indazoles. After the Ugi step, the intermediate tetrazoles were not purified but directly heated with triethyl phosphite to form the final indazoles.
Key words
Ugi - tetrazole - phosphite - cadogan - indazole
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References and Notes
General Procedure
for the Synthesis of Indazoles: To a 3 M solution of o-nitrobenzaldehyde (1 mmol) in MeOH
were added successively amine (1.0 equiv), isocyanide (1.0 equiv) and
trimethylsilyl azide (1.0 equiv). The resulting mixture was stirred
at r.t. overnight. After removal of the excess MeOH, the crude tetrazole
product was used as such for the next step. A 2 M solution of tetrazole
(1 mmol) and triethyl phosphite (5.0 equiv) in DMF was heated at
140 ˚C for 10 h. After completion of the reaction, the
solvent was evaporated under reduced pressure and the crude product
was purified by flash chromatography on silica gel.
3-(1-Cyclohexyl-1
H
-tetrazol-5-yl)-2-propyl-2
H
-indazole (2a):
Prepared on a 1-mmol scale according to the general procedure, 2a was isolated as a yellow solid in 62% yield; mp
110-111 ˚C; R
f
0.3 (petroleum ether-Et2O,
20:80). ¹H NMR (400 MHz, CDCl3): δ = 7.85
(d, J = 8.6 Hz, 1 H), 7.39 (t, J = 7.8 Hz, 1 H), 7.34 (d, J = 8.6 Hz, 1 H), 7.23 (t, J = 7.8 Hz, 1 H), 4.48 (t, J = 7.3 Hz, 2 H), 4.19-4.29
(m, 1 H), 2.05-2.18 (m, 2 H), 1.82-2.03 (m, 6
H), 1.63-1.72 (m, 1 H), 1.15-1.33 (m, 3 H), 0.88
(t, J = 7.3 Hz, 3 H). ¹³C
NMR (100.6 MHz, CDCl3): δ = 148.1,
145.5, 126.5, 124.4, 122.1, 118.7, 117.5, 117.4, 58.7, 53.7, 33.4,
25.1, 24.5, 24.1, 11.0. IR (thin film): 2937, 2857, 1574, 1500,
1454, 1411, 1354, 1095, 1005 cm-¹.
HRMS: m/z calcd
for C17H22N6: 310.1906; found: 310.1901.