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Compound 3 (255 mg, 1.88 mmol) was dissolved in 10 mL POCl3 and stirred at 110 °C for 3 h until a clear solution was obtained. Excess POCl3 was removed in vacuum and ice was added, followed by adding aqueous ammonia until reaching a pH around 9 and an equivalent amount of MeOH was added. Some precipitate formed and was filtered off, and the filtrate was adsorbed on silica and purified by silica gel chromatography (EA with 5percent MeOH) affording 4 in 83percent yield. HRMS (ESI): m/z calcd. for C6H5ClN3 [M+H]+: 154.0166; found, 154.0171.
Reference：
[1] European Journal of Medicinal Chemistry, 2018, vol. 148, p. 384 - 396
[2] ChemMedChem, 2013, vol. 8, # 6, p. 985 - 993
[3] Patent: US5057517, 1991, A,
2
[ 91184-02-0 ]
[ 3243-24-1 ]
Reference：
[1] Journal of the American Chemical Society, 2004, vol. 126, # 31, p. 9532 - 9533
With 3-chloro-benzenecarboperoxoic acid; In methanol; dichloromethane; at 0 - 20℃; for 22h;
Compound 2 (2.5 g, 20.83 mmol) was dissolved in a mixture of 60 mL DCM + 30 mL of MeOH and 10.3 g of m-CPBA (41.67?mmol) dissolved in methanol was added dropwise at 0?C. The reaction was stirred at room temperature for 22?h, after which the mixture was concentrated in vacuum. Methanol (30?mL) was added to the residue which was adsorbed on silica. The title compound 3 was isolated via silica gel chromatography using EA/MeOH (65:35) in 80% yield. 1H NMR (300?MHz, DMSO-d6) delta 8.68 (d, J?=?1.5?Hz, 1H), 8.39 (s, 1H), 8.07 (dd, J?=?6.9, 1.8?Hz, 1H), 7.64 (d, J?=?6.9?Hz, 1H). 13C NMR (75?MHz, DMSO) delta 147.96, 137.85, 136.67, 133.51, 128.35, 111.77. HRMS (ESI): m/z calcd. for C6H6N3O [M+H]+: 136.0505; found, 136.0510.
EXAMPLE 17 1H-Imidazo[4,5-c]pyridine-5-oxide 1H Imidazo[4,5-c]pyridine (4.0 g, 33.6 mmol) was dissolved in 60 ml of fresh acetic acid, heated to 73 C.+-1 C. and to the solution was added 8.8 ml of 30% H2 O2 (78 mmol). After stirring and heating at 73 C. for 24 hrs, an additional 5 ml of H2 O2 was added as well as 1 ml of trifluoroacetic acid. Heating at 73 C. was continued for an additional 3 days. After concentrating, an aliquot NMR (D2 O) shows a 2:1 product: starting material mixture. Concentration of the main reaction mixture was followed by trituration of the residue with 50 ml of acetonitrile. The filtered insolubles 1.6 g (35%) are pure N-oxide by TLC, (reverse phase, 9:1 H2 O:THF) 200 MHz NMR (D2 O, delta from TSP): 7.82 (1H, d, J=7 Hz) 8.21 (1H, d of d, J=7 Hz, J=1 Hz) 8.52 (1H, s) 8.84 (1H, d, J=1).
Compound 3 (255?mg, 1.88?mmol) was dissolved in 10?mL POCl3 and stirred at 110?C for 3?h until a clear solution was obtained. Excess POCl3 was removed in vacuum and ice was added, followed by adding aqueous ammonia until reaching a pH around 9 and an equivalent amount of MeOH was added. Some precipitate formed and was filtered off, and the filtrate was adsorbed on silica and purified by silica gel chromatography (EA with 5% MeOH) affording 4 in 83% yield. HRMS (ESI): m/z calcd. for C6H5ClN3 [M+H]+: 154.0166; found, 154.0171.
In ethanol; chloroform; water; trichlorophosphate;
EXAMPLE 18 4-Chloroimidazo-(4,5-c)pyridine 2.84 g (21 mmol) of imidazo(4,5-c)pyridine-5-oxide was dissolved in 200 ml of freshly distilled POCl3 and refluxed for 16 hrs. The insolubles (starting material, approx. 0.8 g) were filtered and the excess POCl3 was then removed by distillation and the residue was dissolved in 30 ml of H2 O and made basic with concentrated NH3 to pH 8. The solution was extracted 3 times with 30 ml of isoamyl alcohol. This was backwashed with 1 ml of H2 O and concentrated to give 1 g of product. This was dissolved in 5-10 ml of 1:1 ethanol:CHCl3 and applied to a silica gel column (56 g) packed in 7% ethanol:CHCl3 and then eluted with 15% ethanol:CHCl3. Chromatographically pure material (0.710 g, 22%) was obtained. Based on recovered starting material the yield is 31%. 200 MHz NMR (DMSO, delta from TMS): 7.68 (1H, d, J=6 Hz), 8.20 (1H, d, J=6 Hz) 8.50 (s, 1H).
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