* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With iodine; potassium carbonate In N,N-dimethyl-formamide at 85℃; for 15 h;
Synthesis of 3-Iodo-5-nitro-pyridin-2-ol (CXXI): To a mixture of 2-Hydroxy-5-nitro pyridine (14 g, 99.9 mmol) and potassium carbonate (13.8 g, 99.9 mmol) in N,N- dimethylformamide (100 mL) was added iodine (25.3 g, 99.7 mmol) in a portionwise fashion at room temperature. The resulting reaction mixture was heated at 85 °C for 15 h, before 5 being allowed to cool to room temperature. The progress of the reaction was monitored by TLC. The reaction mixture was diluted with water (150 mL) and then extracted with ethyl acetate (75 mL x 3). The combined organic extracts were washed with brine (150 mL x 3), dried over anhydrous sodium sulfate and concentrated in vacuo. The remaining solid residue was washed with n-hexanes (50 mL x 2) and allowed to dry in a stream of air to afford CXXI 10 (14 g, 53percent) as a brown solid, which was used without further purification.
Reference：
[1] Australian Journal of Chemistry, 2008, vol. 61, # 6, p. 438 - 445
[2] Patent: WO2015/73528, 2015, A1, . Location in patent: Page/Page column 191
[3] Journal of Medicinal Chemistry, 2002, vol. 45, # 13, p. 2841 - 2849
[4] Fortschr. Teerfarbenfabr. Verw. Industriezweige, 1930, vol. 17, p. 2439
[5] Patent: US1753170, 1926, ,
[6] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 17, p. 2439
2
[ 5418-51-9 ]
[ 25391-58-6 ]
Reference：
[1] Patent: US2004/77605, 2004, A1,
3
[ 25391-58-6 ]
[ 25391-60-0 ]
Yield
Reaction Conditions
Operation in experiment
94.4%
at 80℃; for 3 h;
2-Hydroxy-3-iodo-5-nitropyridine (1.0 g, 3.76mmol) and phosphorus oxychloride (3.5 g, 11.28mmol) were charge, and the temperature was raised to 80°C. The reaction was carried out at 80°C for 3 hours and the mixture was poured into ice water. The precipitated crystals were filtered to give the title compound (1.01 g, 94.4percent).
81%
With trichlorophosphate In quinoline at 120℃; for 2 h;
Synthesis of 2-Chloro-3-iodo-5-nitro-pyridine (CXXII): To a solution of CXXI (14 g, 52.6 mmol) in quinoline (5 mL) was added phosphorous oxychloride (4.8 mL, 52.2 mmol). The resulting mixture was heated at 120 °C for 2 h. Progress of the reaction was monitored by 15 TLC. After cooling to room temperature the reaction mixture was poured onto ice cold water (75 mL) and the precipitate that formed was collected by filtration. The filtered solid was washed with water and allowed to dry to obtain CXXII (12 g, 81percent) as a brown solid.1H NMR (400 MHz, CDCl3): δ 9.12 (d, J= 2.3 Hz, 1H), 8.84 (d, J= 2.4 Hz, 1H).
69%
at 140℃; for 0.75 h;
Intermediate 1; 6-Phenyl-5-(trifluoromethyl)pyridin-3-amineA. 2-Chloro-3-iodo-5-nitropyridineA mixture of 3-iodo-5-nitropyridin-2-ol (37.60 mmol, 10 g), POCI3 (86.47 mmol, 7.94 ml) and PCI5 (48.87 mmol, 10.2 g) was heated at 14O0C for 45 minutes under argon atmosphere. The mixture was cooled at room temperature, poured slowly over iced-water and extracted with dichloromethane. The organic phase was washed with water, NaHCO3 aqueous solution and brine. The solvent was evaporated and the crude mixture was purified by chromatography over SiO2 eluting hexane/DCM mixtures affording 7.32 g (yield 69percent) of the expected product. <n="39"/>1H NMR (300 MHz, CDCI3) δ ppm: 8.90 (s, 1 H), 9.19 (s, 1H). Intermediate 4A. 2-Chloro-3-iodo-5-nitropyridineA mixture of 3-iodo-5-nitropyridin-2-ol (37.6 mmol, 10 g), POCI3 (86.47 mmol, 7.94 ml) and PCI5 (48.87 mmol, 10.2 g) was heated at 14O0C for 1h, under argon atmosphere. The crude mixture was poured into a mixture of ice and water and extracted with DCM. The solid residue was purified by chromatography over SiO2 eluting with hexane/dichloromethane mixtures affording 2-chloro-3-iodo-5-nitropyridine (7.32 g, yield69percent) of the expected product. 1H NMR (300 MHz, CDCI3) δ ppm: 8.91 (d, J=2.47 Hz, 1H) 9.19 (d, J=2.47 Hz, 1H). Intermediate 606-Chloro-5-(trifluoromethyl)pyridin-3-amineA. 2-Chloro-3-iodo-5-nitropyridine A mixture of 3-iodo-5-nitropyridin-2-ol (37.60 mmol, 10 g), POCI3 (86.47 mmol, 7.94 ml) and PCI5 (48.87 mmol, 10.2 g) was heated at 14O0C for 45 minutes under argon atmosphere. The mixture was cooled at room temperature, poured slowly over iced-water and extracted with dichloromethane. The organic phase was washed with water, NaHCO3 aqueous solution and brine. The solvent was evaporated and the crude mixture was purified by chromatography over SiO2 eluting hexane/DCM mixtures affording 7.32 g (yield 69percent) of the expected product. δ 1H NMR (300 MHz, CDCI3): 8.90 (s, 1H), 9.19 (s, 1H).
Reference：
[1] Australian Journal of Chemistry, 2008, vol. 61, # 6, p. 438 - 445
[2] Patent: EP2599771, 2013, A1, . Location in patent: Paragraph 0505
[3] Patent: WO2015/73528, 2015, A1, . Location in patent: Page/Page column 191
[4] Journal of Medicinal Chemistry, 2002, vol. 45, # 13, p. 2841 - 2849
[5] Patent: WO2009/21696, 2009, A1, . Location in patent: Page/Page column 37-38; 41; 69
[6] Patent: WO2007/65662, 2007, A2, . Location in patent: Page/Page column 47-48
[7] Patent: WO2008/79965, 2008, A1, . Location in patent: Page/Page column 78-79
4
[ 25391-58-6 ]
[ 10026-13-8 ]
[ 25391-60-0 ]
Reference：
[1] Patent: US2004/77605, 2004, A1,
5
[ 25391-58-6 ]
[ 697300-68-8 ]
Reference：
[1] Journal of Medicinal Chemistry, 2004, vol. 47, # 10, p. 2453 - 2465
With iodine; potassium carbonate; In N,N-dimethyl-formamide; at 85℃; for 15h;
Synthesis of 3-Iodo-5-nitro-pyridin-2-ol (CXXI): To a mixture of 2-Hydroxy-5-nitro pyridine (14 g, 99.9 mmol) and potassium carbonate (13.8 g, 99.9 mmol) in N,N- dimethylformamide (100 mL) was added iodine (25.3 g, 99.7 mmol) in a portionwise fashion at room temperature. The resulting reaction mixture was heated at 85 C for 15 h, before 5 being allowed to cool to room temperature. The progress of the reaction was monitored by TLC. The reaction mixture was diluted with water (150 mL) and then extracted with ethyl acetate (75 mL x 3). The combined organic extracts were washed with brine (150 mL x 3), dried over anhydrous sodium sulfate and concentrated in vacuo. The remaining solid residue was washed with n-hexanes (50 mL x 2) and allowed to dry in a stream of air to afford CXXI 10 (14 g, 53%) as a brown solid, which was used without further purification.
2-Hydroxy-3-iodo-5-nitropyridine (1.0 g, 3.76mmol) and phosphorus oxychloride (3.5 g, 11.28mmol) were charge, and the temperature was raised to 80C. The reaction was carried out at 80C for 3 hours and the mixture was poured into ice water. The precipitated crystals were filtered to give the title compound (1.01 g, 94.4%).
81%
With trichlorophosphate; In quinoline; at 120℃; for 2h;
Synthesis of 2-Chloro-3-iodo-5-nitro-pyridine (CXXII): To a solution of CXXI (14 g, 52.6 mmol) in quinoline (5 mL) was added phosphorous oxychloride (4.8 mL, 52.2 mmol). The resulting mixture was heated at 120 C for 2 h. Progress of the reaction was monitored by 15 TLC. After cooling to room temperature the reaction mixture was poured onto ice cold water (75 mL) and the precipitate that formed was collected by filtration. The filtered solid was washed with water and allowed to dry to obtain CXXII (12 g, 81%) as a brown solid.1H NMR (400 MHz, CDCl3): delta 9.12 (d, J= 2.3 Hz, 1H), 8.84 (d, J= 2.4 Hz, 1H).
69%
With phosphorus pentachloride; trichlorophosphate; at 140℃; for 0.75h;Product distribution / selectivity;
Intermediate 1; 6-Phenyl-5-(trifluoromethyl)pyridin-3-amineA. 2-Chloro-3-iodo-5-nitropyridineA mixture of <strong>[25391-58-6]3-iodo-5-nitropyridin-2-ol</strong> (37.60 mmol, 10 g), POCI3 (86.47 mmol, 7.94 ml) and PCI5 (48.87 mmol, 10.2 g) was heated at 14O0C for 45 minutes under argon atmosphere. The mixture was cooled at room temperature, poured slowly over iced-water and extracted with dichloromethane. The organic phase was washed with water, NaHCO3 aqueous solution and brine. The solvent was evaporated and the crude mixture was purified by chromatography over SiO2 eluting hexane/DCM mixtures affording 7.32 g (yield 69%) of the expected product. <n="39"/>1H NMR (300 MHz, CDCI3) delta ppm: 8.90 (s, 1 H), 9.19 (s, 1H). Intermediate 4A. 2-Chloro-3-iodo-5-nitropyridineA mixture of <strong>[25391-58-6]3-iodo-5-nitropyridin-2-ol</strong> (37.6 mmol, 10 g), POCI3 (86.47 mmol, 7.94 ml) and PCI5 (48.87 mmol, 10.2 g) was heated at 14O0C for 1h, under argon atmosphere. The crude mixture was poured into a mixture of ice and water and extracted with DCM. The solid residue was purified by chromatography over SiO2 eluting with hexane/dichloromethane mixtures affording 2-chloro-3-iodo-5-nitropyridine (7.32 g, yield69%) of the expected product. 1H NMR (300 MHz, CDCI3) delta ppm: 8.91 (d, J=2.47 Hz, 1H) 9.19 (d, J=2.47 Hz, 1H). Intermediate 606-Chloro-5-(trifluoromethyl)pyridin-3-amineA. 2-Chloro-3-iodo-5-nitropyridine A mixture of <strong>[25391-58-6]3-iodo-5-nitropyridin-2-ol</strong> (37.60 mmol, 10 g), POCI3 (86.47 mmol, 7.94 ml) and PCI5 (48.87 mmol, 10.2 g) was heated at 14O0C for 45 minutes under argon atmosphere. The mixture was cooled at room temperature, poured slowly over iced-water and extracted with dichloromethane. The organic phase was washed with water, NaHCO3 aqueous solution and brine. The solvent was evaporated and the crude mixture was purified by chromatography over SiO2 eluting hexane/DCM mixtures affording 7.32 g (yield 69%) of the expected product. delta 1H NMR (300 MHz, CDCI3): 8.90 (s, 1H), 9.19 (s, 1H).
With quinoline; trichlorophosphate; at 20 - 120℃; for 2h;
K1 ) 2-Chloro-3-iodo-5-nitro-pyridine; :<strong>[25391-58-6]2-hydroxy-3-iodo-5-nitropyridine</strong> (2.0 g, 7.52 mmol) is added to a mixture of POCI3 (0.7 ml, 7.52 mmol) and quinoline (0.44 ml, 3.76 mmol) at room temperature. The <n="49"/>reaction mixture is heated at 120 0C for 2 h. The reaction mixture is then cooled to 96 0 C and is carefully quenched by the dropwise addition of water (32 ml). The reaction mixture is cooled to room temperature and filtered. The solid collected is dissolved in EtOAc and dried (MgSO4) then concentrated in vacuo to yield the title compound.
Example 70: N-[6-methyl-5-(9H-pyrimido[4,5-b]indol-7-yl)pyridin-3-yl]-3- (trifluoromethyl)benzamide <n="80"/>Stepl : 2-chloro-3-iodo-5-nitropyridine3-Iodo-5-nitropyridin-2-ol (3.00 g, 0.0113 mol) was heated to reflux in phosphoryl chloride(15 mL, 0.1609 mol) for 4 hours. The reaction was quenched in ice/water and was neutralized with Na2CO3. The reaction was extracted with ethyl acetate and the organic extracts were washed with water, saturated NaCl, dried (MgSO4) and stripped in vacuo to give the product, which was used in the next reaction without purification
With potassium acetate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 120℃; for 17h;
5-Nitro-3-thiazol-5-yIpyridin-2-ol; NO2[787] N2 was bubbled through a solution of <strong>[25391-58-6]3-iodo-5-nitropyridin-2-ol</strong> (1.33g,S.OOmmol), thiazole (2.13g, 25.0mmol), potassium acetate (1.47g, IS.Ommol), andtetrakis(triphenylphosphine)palladium(0) (0.4g, 0.4mmol) in DMF (lOmL) for 10 min. Themixture was then heated to 120C and stirred for 17h. The solvents were removed in vacua.The residue was stirred with methanol (5mL) and dichloromethane (lOmL) for 30min. Thesolids were collected by filtration, washed with dichloromethane (2mL) and water (3x8mL),and dried in vacua to afford the title compound as an off-white solid. ^-NMR (DMSO-d6,400 MHz): 8 = 8.74 (d, J= 2.8 Hz, 1 H), 8.77 (s, 1 H), 8.79 (d, J= 2.8 Hz, 1 H), 9.12 (s, 1 H),13.26 (s, br, 1 H). MS (ES+): m/z 224.09 [MH*]. HPLC: tR = 2.16 min (ZQ2000,polar_5min).
B. 2-Chloro-3-iodo-5-nitropyridine (765B) 2-Hydroxy-3-iodo-5-nitropyridine (2.55 g, 9.5 mmol), phosphorous pentachloride (2.60 g, 12 mmol) and phosphorous oxychloride (2 mL) were combined in a flask under nitrogen and heated to 140 C. for 45 mins. The cooled reaction mixture was poured over ice to give a solid which was partitioned between CH2Cl2 and water. The organic layer was separated, washed with brine, dried (MgSO4), filtered, and the solvent was removed in vacuo to give compound 765B (2.25 g, 83%) as a yellow solid. HPLC: 98.5% at 2.75 min(YMC S5 ODS column) eluding with 10-90% aqueous methanol containing 0.2% phosphoric acid over a 4 min gradient monitoring at 220 nm.
With potassium iodate; potassium iodide; In sulfuric acid; water;
A. 2-Hydroxy-3-iodo-5-nitropyridine (765A) 2-Hydroxy-5-nitropyridine (7.0 g, 50 mmol) was suspended in 100 mL of 20% sulfuric acid and then treated with potassium iodate (4.2 g, 19.6 mmol) dissolved in 10 mL of water. The mixture was heated to 100 C. and potassium iodide (8.0 g, 48.2 mmol) dissolved in 20 mL of water was added dropwise over one h. The reaction mixture turns a purplish-red and a precipitate forms. After 0.5 h, the reaction mixture is cooled and filtered. The solid is stirred for 15 min with 10% sodium meta-bisulfite solution, filtered, washed with water and dried at 80 C. overnight on a vacuum pump to give the desired compound 765A (12.32 g, 92%) as a yellow solid. The product was characterized by 1H NMR.
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 2h;
Example 1.9: Preparation of Intermediate 4-[2-(3-Iodo-5-nitro-pyridin-2-yloxy)-ethyl]- morpholine.To a suspension of <strong>[25391-58-6]3-iodo-5-nitro-pyridin-2-ol</strong> (1.95 g, 7.32 mmol) in THF (60 mL), triphenyl phosphine (4.09 g, 15.6 mmol) and 4-(2-hydroxyethyl)motaupholine (1.90 mL, 15.6 mmol) were added followed by dropwise addition of diisopropyl azodicarboxylate (DIAD) (3.00 mL, 15.5 mmol). After 1 hour, an LC/MS showed only partial conversion so extra triphenyl phosphine (2.73'g, 10.4 mmol) and 4-(2-hydroxyethyl)morpholine (1.30 mL, 10.7 mmol) were added followed by dropwise addition of diisopropyl azodicarboxylate (DIAD) (2.00 mL, 10.3 mmol). The reaction mixture was stirred at room temperature for 1 more hour and then concentrated. The resulting gummy residue was dissolved in water (500 mL), acidified with HCl to pH 1 , washed with ethyl acetate (three 300 mL portions, which were discarded), basified to pH 10 with NaOH, and extracted three times with 300 mL portions of ethyl acetate. The combined organic phase was dried over MgSO4, filtered and concentrated, yielding an oil which was purified by HPLC to afford 4-[2-(3-iodo-5-nitro-pyridin-2-yloxy)-ethyl] -morpholine as an impure brown oil (1.06 g). LCMS m/z (%) = 380 (M+H, 100). 1H NMR (400 MHz, DMSO-de) delta: 9.04 (d, J= 2.63 Hz, IH), 8.87 (d, J= 2.60 Hz, IH), 4.55 (t, J= 5.61 Hz, 2H), 3.58-3.50 (m, 4H), 2.75 (t, /= 5.59 Hz, 2H), 2.43-2.30 (m, 4H).
With silver carbonate; In toluene; at 70℃; for 6h;
Intermediate 26; 6-(Benzyloxy)-5-phenylpyiotadin-3-amineA. 2-(Benzyloxy)-3-iodo-5-nitropyridineTo a solution of <strong>[25391-58-6]3-iodo-5-nitropyridin-2-ol</strong> (0.011 mol, 3 g) in 30 ml of toluene, 2.5 ml of (bromomethyl)benzene and 5.1 g of Ag2CO3 was added. The mixture was stirred at 7O0C for 6h. The crude was filtered through Celite and washed with ethyl acetate. The solvent was evaporated affording 3.6 g (yield 90%) of the expected product.1H NMR (300 MHz, CDCI3) delta ppm: 5.56 (s, 2H), 7.33 - 7.46 (m, 3H), 7.46 - 7.54 (m,2H), 8.84 (d, 1 H), 9.03 (d, 1 H).
With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 100℃; for 4h;
Intermediate 3; <n="41"/>6-Methoxy-5-phenylpyridin-3-amineA. 5-Nitro-3-phenylpyridin-2-olIn a schlenck tube, a mixture of <strong>[25391-58-6]3-iodo-5-nitropyridin-2-ol</strong> (7.52 mmol, 2 g), phenylboronic acid (8.28 mmol, 1.01 g), PdCI2dppf.DCM (0.75 mmol, 0.6 g), Cs2CO3 (22.56 mmol, 7.4 g) in a dioxane/water 4:1 mixture (26 ml) was heated at 1000C for 4 hours, under argon atmosphere. The solvent was evaporated and the crude mixture was extracted between water and ethyl acetate. The organic phase was evaporated and the crude was suspended in methanol affording a solid that was filtered off and dried under vacuum overnight affording 1.2 g (74% of yield) of the expected product.1H NMR (300 MHz, CDCI3) delta ppm:: 7.31 - 7.54 (m, 3H), 7.61 - 7.76 (m, 2H), 8.26(d, 1H), 8.44 (s, 1 H).ESI/MS (m/e, %): 215 [(M-1)', 100].
With lithium hydroxide monohydrate; In 1,2-dimethoxyethane; at 5 - 20℃; for 2h;
Preparation of 3-lodo-5-nitro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyridin-2- one (1 a).2-Hydroxy-3-iodo-5-nitro pyridine (26.6g, lOOmmol) was stirred in anhydrous 1 ,2- dimethoxyethane (50OmL) at ambient temperature and lithium hydroxide monohydrate (8.5g, 203mmol) was added. The reaction mixture was cooled to 50C using ice/water and then 2-(trimethylsilyl)ethoxymethyl chloride (18.84g, 2OmL, 113mmol) was added dropwise and the reaction stirred at ambient temperature for 2 hours. The reaction mixture was diluted with diethyl ether (100OmL) and the mixture washed with 2M aqueous sodium hydroxide solution (2x200mL) and then 20% aqueous sodium thiosulphate solution (20OmL) and finally water (3x200mL). The solution was dried over anhydrous sodium sulphate and concentrated to an orange oil. The resultant crude product was purified by flash chromatography on SiO2 eluting with hexane - 20% ethyl acetate / hexane (gradient). The title compound was isolated as a yellow oil, 26.9g, 68%.
With potassium carbonate; In acetone; at 60℃; for 3h;
To acetone (19ml), <strong>[25391-58-6]2-hydroxy-3-iodo-5-nitropyridine</strong> (1.0 g, 3.76mmol), methyl iodide (0.58 g, 4.14mmol) and potassium carbonate (1.0 g, 7.52mmol) were added, and reacted at 60C for 3 hours. The mixture was cooled to room temperature and crystallized (-out) with addition of water. The precipitated crystals were filtered to give the title compound (0.88 g, 83.5%).
5-nitro-3-(2H-1,2,3-triazol-2-yl)pyridin-2-ol[ No CAS ]
5-nitro-3-(1H-1,2,3-triazol-1-yl)pyridin-2-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With copper(l) iodide; 2,2,6,6-tetramethylheptane-3,5-dione; caesium carbonate; In water; dimethyl sulfoxide; ethyl acetate; at 155℃; for 1h;Inert atmosphere; Enzymatic reaction;
1st Step Cesium carbonate (24.4 g), 1,2,3-triazole (4.35 ml), 2,2,6,6-tetramethyl-3,5-heptanedione (3.89 ml), and copper iodide (7.1 g) were added to a DMSO (100 ml) solution containing <strong>[25391-58-6]3-iodo-5-nitropyridin-2-ol</strong> (10 g) in a nitrogen atmosphere, followed by stirring at 155 C. for 1 hour. The reaction solution was adjusted to room temperature and water was added to the reaction solution. An insoluble precipitate was removed by filtration. 1M hydrochloric acid (110 ml) was added to the resulting filtrate so as to acidify the reaction solution, followed by extraction with ethyl acetate. The organic layers were washed with saturated saline and dried over anhydrous sodium sulfate and the solvent was distilled away under reduced pressure. Ethyl acetate was added to the obtained residue and insoluble matter was collected by filtration. A yellow solid mixture (4.86 g) of 5-nitro-3-(2H-1,2,3-triazol-2-yl)pyridin-2-ol and 5-nitro-3-(1H-1,2,3-triazol-1-yl)pyridin-2-ol was thus obtained.
With copper(l) iodide; 2,2,6,6-tetramethylheptane-3,5-dione; caesium carbonate; In dimethyl sulfoxide; at 155℃; for 1h;Inert atmosphere;
1st Step Cesium carbonate (24.4 g), 1,2,3-triazole (4.35 ml), 2,2,6,6-tetramethyl-3,5-heptanedione (3.89 ml), and copper iodide (7.1 g) were added to a DMSO (100 ml) solution containing <strong>[25391-58-6]3-iodo-5-nitropyridin-2-ol</strong> (10 g) in a nitrogen atmosphere, followed by stirring at 155 C. for 1 hour. The reaction solution was adjusted to room temperature and water was added to the reaction solution. An insoluble precipitate was removed by filtration. 1M hydrochloric acid (110 ml) was added to the resulting filtrate, followed by extraction with ethyl acetate. The organic layers were washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure, a small amount of ethyl acetate was added to the obtained residue, and insoluble matter was collected by filtration. A yellow solid mixture (4.86 g) of 5-nitro-3-(2H-1,2,3-triazol-2-yl)pyridin-2-ol and 5-nitro-3-(1H-1,2,3-triazol-1-yl)pyridin-2-ol was thus obtained.
184 mg
With copper(l) iodide; caesium carbonate; dimethyl sulfoxide; L-proline; at 100℃; for 3h;Inert atmosphere;
Cesium carbonate (550 mg), L-proline (65 mg), and 1H-1,2,3-triazole (92 mg) were added to a dimethyl sulfoxide (3 ml) solution containing <strong>[25391-58-6]2-hydroxy-3-iodo-5-nitropyridine</strong> (300 mg), and copper iodide (106 mg) was further added in a nitrogen atmosphere, followed by stirring at 100C for 3 hours. The reaction solution was adjusted to room temperature. Water and ethyl acetate were added. The pH was adjusted to pH 7 with 1M hydrochloric acid. Insoluble matter was filtered, followed by extraction with ethyl acetate (x3). The resultant was washed with saturated saline and dried over anhydrous sodium sulfate. Subsequently, the solvent was distilled away under reduced pressure, the obtained residue was purified by silica gel chromatography (chloroform : methanol = 1:0 to 10:1), and an orange solid of a mixture (184 mg) of 5-nitro-3-(2H-1,2,3-triazol-2-yl)pyridin-2-ol and 5-nitro-3-(1H-1,2,3-triazol-1-yl)pyridin-2-ol was thus obtained.
5-nitrofuro[2,3-b]pyridine-2-2-MIDA boronate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triphenylphosphine; N,N,N',N'-tetramethylguanidine; In N,N-dimethyl-formamide; at 50℃; for 22h;Inert atmosphere;
General procedure: Dry DMF (6.0 mL) was added to methyl 4-hydroxy-3-iodobenzoate (0.56 g, 2.0 mmol), ethynylboronic acid MIDA ester (0.47 g, 2.6 mmol), CuI (38 mg, 0.20mmol), PdCl2(Ph3P)2 (70 mg, 0.10 mmol) and Ph3P (52 mg, 0.20 mmol) under N2. 1,1,3,3-Tetramethylguanidine(TMG) (0.30 mL, 2.4 mmol) was added to the resulting solution under N2. The reactionmixture was stirred at 50 Cfor 22 h under N2. The resulting mixture was diluted with water to form aprecipitate, which was filtered, washed with water and dried at room temperature. The obtained solid was dissolved in acetone and purified by flash chromatography (SiO2, CH2Cl2 : MeOH = 10 : 1). The eluted material was washed with hot EtOH and dried to give 1A (493.6 mg, 75%) as a pale brown solid;
With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; N,N-dimethyl acetamide; water; at 120℃; for 17.5h;Inert atmosphere;
1st step Cesium carbonate (3.6 g), cyclopropylboronic acid·monohydrate (1.0 g), tetrakis(triphenylphosphine)palladium (0.87 g), and water (0.2 ml) were added to a 1,4-dioxane (20 ml) solution containing <strong>[25391-58-6]2-hydroxy-3-iodo-5-nitropyridine</strong> (2.00 g) in a nitrogen atmosphere, followed by stirring for 10 hours. Then, N,N-dimethylacetamide (10 ml) was added to the reaction solution, followed by stirring at 120C for 7.5 hours. The reaction solution was adjusted to room temperature and the pH was adjusted to pH 2 with the addition of water and 6M hydrochloric acid, followed by extraction with ethyl acetate. The resultant was washed with saturated saline and dried over anhydrous sodium sulfate, the solvent was distilled away under reduced pressure, the obtained residue was purified by silica gel chromatography (n-hexane : ethyl acetate = 3:1 to 0:1), and a white solid of 2-hydroxy-5-nitro-3-cyclopropylpyridine (0.41 g) was thus obtained. MS (ESI m/z): 181 (M+H) RT (min): 1.04
1-methyl-5-nitro-3-(2H-1,2,3-triazol-2-yl)pyridin-2(1H)-one[ No CAS ]
1-methyl-5-nitro-3-(1H-1,2,3-triazol-1-yl)pyridin-2(1H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
184 mg
Cesium carbonate (550 mg), L-proline (65 mg), and 1H-1,2,3-triazole (92 mg) were added to a dimethyl sulfoxide (3 ml) solution containing <strong>[25391-58-6]2-hydroxy-3-iodo-5-nitropyridine</strong> (300 mg), and copper iodide (106 mg) was further added in a nitrogen atmosphere, followed by stirring at 100C for 3 hours. The reaction solution was adjusted to room temperature. Water and ethyl acetate were added. The pH was adjusted to pH 7 with 1M hydrochloric acid. Insoluble matter was filtered, followed by extraction with ethyl acetate (x3). The resultant was washed with saturated saline and dried over anhydrous sodium sulfate. Subsequently, the solvent was distilled away under reduced pressure, the obtained residue was purified by silica gel chromatography (chloroform : methanol = 1:0 to 10:1), and an orange solid of a mixture (184 mg) of 5-nitro-3-(2H-1,2,3-triazol-2-yl)pyridin-2-ol and 5-nitro-3-(1H-1,2,3-triazol-1-yl)pyridin-2-ol was thus obtained.
2-hydroxy-5-nitro-3-(1H-pyrazol-1-yl)pyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
1.02 g
With copper(l) iodide; dimethylaminoacetic acid; caesium carbonate; In N,N-dimethyl acetamide; at 90℃; for 2.5h;Inert atmosphere;
Pyrazole (0.60 g), cesium carbonate (3.6 g), N,N-dimethylglycine (0.76 g), and copper iodide (I) (0.76 g) were added to an N,N-dimethylacetamide (20 ml) solution containing <strong>[25391-58-6]2-hydroxy-3-iodo-5-nitropyridine</strong> (2.00 g) in a nitrogen atmosphere, followed by stirring at 90C for 2.5 hours. The reaction solution was adjusted to room temperature, water and ethyl acetate were added, and an insoluble precipitate was removed. The pH was adjusted to pH 2 with the addition of 6M hydrochloric acid. Then, organic layer was washed with saturated saline and dried over anhydrous sodium sulfate, the solvent was distilled away under reduced pressure. Ethyl acetate was added to the obtained residue, a solid precipitate was collected by filtration, and a green solid of 2-hydroxy-5-nitro-3-(1H-pyrazol-1-yl)pyridine (0.35 g) was thus obtained. Thereafter, the filtrate was collected, the solvent was distilled away under reduced pressure, the obtained residue was purified by silica gel chromatography (n-hexane: ethyl acetate = 3:1 to 0:1), and a light green solid of 2-hydroxy-5-nitro-3-(1H-pyrazol-1-yl)pyridine (1.02 g) was thus obtained. MS (ESI m/z): 207 (M+H) RT (min): 0.94
2-chloro-5-nitro-3-(2H-1,2,3-triazol-2-yl)pyridine[ No CAS ]
2-chloro-5-nitro-3-(1H-1,2,3-triazol-1-yl)pyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
177 mg; 83 mg
Thionyl chloride (3.9 ml) and DMF (0.39 ml) were added to a mixture of 2-hydroxy-5-nitro-3-(2H-1,2,3-triazol-2-yl)pyridine and 2-hydroxy-5-nitro-3-(1H-1,2,3-triazol-1-yl)pyridine (385 mg), followed by stirring at 90C for 2 hours.The reaction solution was adjusted to room temperature, slowly added to ice water, and stirred under ice cooling for 30minutes, followed by extraction with ethyl acetate. Then, the resultant was washed with saturated saline and dried overanhydrous sodium sulfate. The solvent was distilled away under reduced pressure, the obtained residue was purifiedby silica gel chromatography (n-hexane : ethyl acetate = 9:1 to 2:1), and a yellow solid of 2-chloro-5-nitro-3-(2H-1,2,3-triazol-2-yl)pyridine (177 mg) and a yellow solid of 2-chloro-5-nitro-3-(1H-1,2,3-triazol-1-yl)pyridine (83 mg) were thusobtained.2-Chloro-5-nitro-3-(2H-1,2,3-triazol-2-yl)pyridineMS (ESI m/z): 226, 228 (M+H)RT (min): 1.101H-NMR (DMSO-d6, 300MHz) delta:9.32 (d, 1H, J = 2.5Hz), 8.85 (d, 1H, J = 2.5Hz), 8.01 (s, 2H)2-Chloro-5-nitro-3-(1H-1,2,3-triazol-1-yl)pyridineMS (ESI m/z): 226, 228 (M+H)RT (min): 0.841H-NMR (DMSO-d6, 300MHz) delta:9.38 (d, 1H, J = 2.3Hz), 8.90 (d, 1H, J = 2.3Hz), 8.26 (d, 1H, J = 1.0Hz), 7.97 (d, 1H, J= 1.0Hz).
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