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Structure of 4008-48-4 * Storage: {[proInfo.prStorage]}
* 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.
Reference:
[1] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 1, p. 478 - 487
2
[ 63450-86-2 ]
[ 4008-48-4 ]
Yield
Reaction Conditions
Operation in experiment
90.1%
With nitric acid In water at 17℃; for 1.41667 h; Inert atmosphere; Cooling with ice
The oxidation of 8-hydroxy-5-nitrosoquinoline (10) to 8-hydroxy-5-nitroquinoline(11 ) was carried out according to the procedure ofPetrow and Sturgeon20. Finely grounded 8-hydroxy-5-nitrosoquinoline hydrochloride (10) (15.0 g, 0.7mmol) was added into a 500 mL beaker containingconcentrated nitric acid (45 mL) and water (30 mL)in an ice bath. The mixture was stirred for 85 min at17 °C. Equal volume of cold water was added andthe mixture cooled to 0 °C and alkaline was madewith cold concentrated potassium hydroxidesolution pH 13.0. The red potassium salt wasdecomposed on neutralization with acetic acid,filtered by suction and washed with water. Theresidue was recrystallized from ethanol to afford abright yellow crystal of 8-hydroxy-5-nitroquinoline.Yield 14.10 g (90.1percent), mp 179 °C (lit 179.5-181.5°C)20.
Reference:
[1] Oriental Journal of Chemistry, 2015, vol. 31, # 1, p. 371 - 378
[2] Russian Journal of Organic Chemistry, 2004, vol. 40, # 1, p. 93 - 96
[3] Asian Journal of Chemistry, 2017, vol. 29, # 4, p. 742 - 748
[4] Journal of Heterocyclic Chemistry, 2017, vol. 54, # 2, p. 1572 - 1577
[5] Medicinal Chemistry Research, 2018, vol. 27, # 4, p. 1093 - 1102
3
[ 148-24-3 ]
[ 4008-48-4 ]
Reference:
[1] ACS Chemical Neuroscience, 2014, vol. 5, # 10, p. 952 - 962
[2] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1997, vol. 36, # 11, p. 1071 - 1073
[3] Chemistry of Heterocyclic Compounds, 2005, vol. 41, # 8, p. 1027 - 1030
[4] Russian Journal of Organic Chemistry, 2004, vol. 40, # 1, p. 93 - 96
[5] Journal fuer Praktische Chemie (Leipzig), 1892, vol. <2> 45, p. 540
[6] Molecules, 2010, vol. 15, # 1, p. 288 - 304
[7] Archives of Pharmacal Research, 2013, vol. 36, # 1, p. 32 - 40
[8] Dalton Transactions, 2015, vol. 44, # 48, p. 20913 - 20925
[9] RSC Advances, 2016, vol. 6, # 9, p. 7139 - 7158
[10] Asian Journal of Chemistry, 2017, vol. 29, # 4, p. 742 - 748
[11] Journal of Heterocyclic Chemistry, 2017, vol. 54, # 2, p. 1572 - 1577
[12] Medicinal Chemistry Research, 2018, vol. 27, # 4, p. 1093 - 1102
[13] Journal of Fluorescence, 2018, vol. 28, # 5, p. 1121 - 1126
4
[ 3565-26-2 ]
[ 4008-48-4 ]
Reference:
[1] Journal of the Chemical Society, 1954, p. 570,572
[2] Acta crystallographica. Section C, Crystal structure communications, 2002, vol. 58, # Pt 1, p. o19-21
[3] Chemistry of Heterocyclic Compounds, 2005, vol. 41, # 8, p. 1027 - 1030
[4] Journal of Fluorescence, 2018, vol. 28, # 5, p. 1121 - 1126
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at -70 - 20℃; for 16h;Inert atmosphere;Product distribution / selectivity;
To a suspension of 5-nitroquinolin-8-ol (2.30 g, 12.2 mmol), triphenylphosphine (4.10 g, 15.8 mmol) and <strong>[105250-17-7](2-aminopyridin-4-yl)methanol</strong> (1 .66 g, 13.4 mmol) in THF (50 mL) under N2 at - 70°C was added DIAD (3.31 mL, 17.0 mmol) and the reaction mixture then warmed to RT for 16 hr. The mixture was evaporated in vacuo and the residue was triturated with MeOH (50 mL), and the solid collected by filtration and washed with MeOH (2 x 50mL) and Et20 (2 x 50mL). The Mitsunobu coupling reaction was then repeated using the following amended protocol: To a suspension of 5-nitroquinolin-8-ol (1 .50 g, 7.90 mmol), triphenylphosphine (3.10 g, 1 1.8 mmol) and <strong>[105250-17-7](2-aminopyridin-4-yl)methanol</strong> (1 .18 g, 9.47 mmol) in THF (25 mL) at RT under N2 was added DIAD (2.15 mL, 1 1.0 mmol), dropwise over 10 min. After 1 hr the reaction mixture was combined with the previously isolated solid and the mixture was purified directly (without further work-up) by flash column chromatography (Si02, 120 g, MeOH in DCM, 1 -10percent, gradient elution) to afford the title compound, Intermediate H2, as a yellow solid (1.5 g, 25 percent); Rl 3.73 min (Method 1 basic); m/z 297 (M+H)+ (ES+).
1.5 g
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 1h;Inert atmosphere;
To a suspension of 5-nitroquinolin-8-ol (2.30 g, 12.2 mmol), triphenylphosphine (4.10 g, 15.8 mmol) and <strong>[105250-17-7](2-aminopyridin-4-yl)methanol</strong> (1.66 g, 13.4 mmol) in THF (50 mL) under N2 at ?70° C. was added DIAD (3.31 mL, 17.0 mmol) and the reaction mixture then warmed to RT for 16 hr. The mixture was evaporated in vacuo and the residue was triturated with MeOH (50 mL), and the solid collected by filtration and washed with MeOH (2×50 mL) and Et2O (2×50 mL). The Mitsunobu coupling reaction was then repeated using the following amended protocol: To a suspension of 5-nitroquinolin-8-ol (1.50 g, 7.90 mmol), triphenylphosphine (3.10 g, 11.8 mmol) and <strong>[105250-17-7](2-aminopyridin-4-yl)methanol</strong> (1.18 g, 9.47 mmol) in THF (25 mL) at RT under N2 was added DIAD (2.15 mL, 11.0 mmol), dropwise over 10 min. After 1 hr the reaction mixture was combined with the previously isolated solid and the mixture was purified directly (without further work-up) by flash column chromatography (SiO2, 120 g, MeOH in DCM, 1-10percent, gradient elution) to afford the title compound, Intermediate H2, as a yellow solid (1.5 g, 25percent); Rt 3.73 min (Method 1 basic); m/z 297 (M+H)+ (ES+).
General procedure: All starting materials and reagents were commercially available and used as received. Formaldehyde (75 mmol) and the cyclic secondary amine (20 mmol) were reacted under cooling on ice and the resulting hard white precipitation was added portionwise to the 8-hydroquinoline derivative (20 mmol) dissolved in 60 mL pyridine under stirring at 50 C. The added precipitate reacted readily and after a couple of minutes a yellowish precipitation was formed. Aftert 30-40 min the mixture was filtered through a Buechner funnel. The precipitate was washed with 150 mL ethanol, dissolved in 1 M HCl under heating and crystallized by addition of 1 M NaOH under gentle stirring until pH 5-6. The crystals were washed with water and the isolated product was >95% pure according to LC-MS and 1H NMR spectroscopy.
6 Production Example 6 Synthesis of Vanadium Complex of Formula (2a-6)
Production Example 6 Synthesis of Vanadium Complex of Formula (2a-6) [0075] 5-Nitro-8-quinolinol (810 mg, 4.3 mmol) was dissolved in acetonitrile (7 mL) followed by the addition of triisopropoxyvanadium(V) oxide (0.5 mL, 2.1 mmol) and stirring for 24 hours at room temperature. The precipitate that formedwas filtered and the resulting solid was washed with diethyl ether followed by drying under reduced pressure to obtaina vanadium complex of the aforementioned formula (2a-6) (974 mg, yield: 91%).[0076] 1H-NMR(400MHz, CDCl3) δ(ppm): 9.45(dd, 1H, J=1.2, 8.8Hz), 9.32(dd, 1H, J=1.3, 8.8Hz), 8.77(d, 1H, J=8.8Hz),8.72(d, 1H, J=8.8Hz), 8.71(dd, 1H, J=1.2, 4.5Hz), 8.50(dd, 1H, J=1.3, 4.5Hz), 7.61(dd, 1H, J=4.5, 8.8Hz), 7.53(dd, 1H,J=4.5, 8.8Hz), 7.20(d, 1H, J=4.5Hz), 7.14(d, 1H, J=4.5Hz), 6.56(sept, 1H, J=6.2Hz), 1.57(d, 3H, J=6.2Hz), 1.50(d, 3H,J=6.2Hz)
4-nitrophenyl 5-nitroquinolin-8-yl phosphorochloridate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With triethylamine; In tetrahydrofuran; at 0 - 65℃; for 4h;
General procedure: 5-Nitroquinolin-8-ol (5) (285.1 mg, 1.5 mmol), and triethylamine (0.27 mL,2.0 mmol) were taken into a round bottom flask (50 mL) containing THF (10 mL). Thereaction mixture was cooled to 0-10C and then <strong>[777-52-6]4-nitrophenyl phosphorodichloridate</strong>s(6) (0.38 mg, 1.5 mmol) in THF (5 mL) was added drop-wise at 10C. The reactionmixture was stirred for 30 min at 10C and the reaction temperature was raised up toreflux (60-65C). It was refluxed for 3.5 h, and completion of the reaction was confirmedby TLC. The reaction mass was cooled to ambient temperature (26-30C) and filteredto remove the salt, Et3N.HCl. The filtrate containing the intermediate, 4-nitrophenyl5-nitroquinolin-8-yl phosphorochloridate (8), was collected and used in the next step.
With dmap; N-ethyl-N,N-diisopropylamine In hexane; dichloromethane at 20℃; for 14h;
3 Example 3 tert-Butyl- (5-nitro-8-quinolinolato) carbonate
5-nitro-8-hydroxyquinoline (10.0 g, 52.6 mmol) and di-tert-butyl carbonate (12.7 g, 57.8 mmol) were dissolved in n-hexane / dichloromethane / V = 1: 2), 4-N, N-dimethylaminopyridine (0.65 g, 5.26 mmol) and diisopropylethylamine (11.2 mL, 63.12 mmol) were added at room temperature with stirring. After stirring 14h, suction filtration and concentration. 0g. Purified by column chromatography to give pale yellow solid 14. 0g. Yield 92%
2 Synthesis of X-2
The specific synthesis operation is as follows: 5-nitro-8-hydroxyquinoline was prepared according to methods reported in the literature.0.5 g (2.63 mmol) of 5-nitro-8-hydroxyquinoline and 0.32 mL of formaldehyde were dissolved in 20 ml of absolute ethanol.To this solution was added 2 equivalents of the corresponding amine.The mixture was refluxed at 80 ° C for 24 h. The reaction solution was filtered to obtain a precipitate, which was then recrystallized from a solution of EtOH:H2O = 1:1 to give the corresponding product. The experimental procedure was the same as in Example 1.
Stage #1: nitroxoline With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.5h; Inert atmosphere;
Stage #2: ethyl bromide In N,N-dimethyl-formamide Inert atmosphere;
(5-nitroquinolin-8-yloxy)methyl 2-ethylbutanoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
14%
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 16h;
5 Example 5: Synthesis of (5-nitroquinolin-8-yloxy)methyl 2-ethylbutyrate (5) 5
At room temperature, potassium carbonate (9.59 g, 69.41 mmol) was added to nitroquinoline (6.00 g, 35.55 mmol), 2-ethylbutyric acid-1 chloromethyl (10.00 g, 60.74 mmol) in N , N-dimethylformamide (100 mL) solution. The reaction solution was stirred at 60°C for 16 hours. The reaction was quenched by adding water, extracted with dichloromethane (100 mL x 3), the organic phase was washed with 1 M hydrochloric acid, 1 M aqueous sodium bicarbonate solution and saturated brine, the organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: 5% n-hexane/95% ethyl acetate) to obtain (5-nitroquinolin-8-yloxy)methyl 2-ethylbutanoic acid Ester (1.4 g, yield 14%).
14%
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 16h; Inert atmosphere;
5 Example 5 Synthesis of (5-nitroquinolin-8-yloxy)methyl 2-ethylbutanoate (5)
Potassium carbonate (9.59 g, 69.41 mmol) was added to a solution of nitroxoline (6.00 g, 35.55 mmol) and 1-chloromethyl 2-ethylbutanoate (10.00 g, 60.74 mmol) in N,N-dimethylformamide (100 mL) in batches at room temperature. The reaction solution was stirred at 60° C. for 16 hours. The reaction was quenched by water, and the solution was extracted with dichloromethane (100 mL*3). The organic phase was washed with 1 M hydrochloric acid, 1 M sodium bicarbonate aqueous solution and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (eluent: 5% hexane/95% ethyl acetate) to obtain (5-nitroquinolin-8-yloxy)methyl 2-ethylbutanoate (1.4 g, yield: 14%). 1H NMR (400 MHz, CD3OD): δ 9.17-9.14 (m, 1H), 8.97-8.95 (m, 1H), 8.55 (d, J=8.8 Hz, 1H), 7.84-7.81 (m, 1H), 7.58 (d, J=8.8 Hz, 1H), 6.21 (s, 2H), 2.34-2.27 (m, 1H), 1.67-1.47 (m, 4H), 0.815 (t, J=7.2 Hz, 6H). MS calculated: 318.1; MS observed: 319.1 [M+H]+.
14%
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 16h; Inert atmosphere;
5 Example 5 Synthesis of (5-nitroquinolin-8-yloxy)methyl 2-ethylbutanoate (5)
Potassium carbonate (9.59 g, 69.41 mmol) was added to a solution of nitroxoline (6.00 g, 35.55 mmol) and 1-chloromethyl 2-ethylbutanoate (10.00 g, 60.74 mmol) in N,N-dimethylformamide (100 mL) in batches at room temperature. The reaction solution was stirred at 60° C. for 16 hours. The reaction was quenched by water, and the solution was extracted with dichloromethane (100 mL*3). The organic phase was washed with 1 M hydrochloric acid, 1 M sodium bicarbonate aqueous solution and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (eluent: 5% hexane/95% ethyl acetate) to obtain (5-nitroquinolin-8-yloxy)methyl 2-ethylbutanoate (1.4 g, yield: 14%). 1H NMR (400 MHz, CD3OD): δ 9.17-9.14 (m, 1H), 8.97-8.95 (m, 1H), 8.55 (d, J=8.8 Hz, 1H), 7.84-7.81 (m, 1H), 7.58 (d, J=8.8 Hz, 1H), 6.21 (s, 2H), 2.34-2.27 (m, 1H), 1.67-1.47 (m, 4H), 0.815 (t, J=7.2 Hz, 6H). MS calculated: 318.1; MS observed: 319.1 [M+H]+.
With potassium carbonate
5 Example 5
Example 5 Synthesis of (5-nitroquinolin-8-yloxy)methyl 2-ethylbutanoate (5) Potassium carbonate (9.59 g, 69.41 mmol) was added to a solution of nitroxoline (6.00 g, 35.55 mmol) and 1-chloromethyl 2-ethylbutanoate (10.00 g, 60.74 mmol) in N,N-dimethylformamide (100 mL) in batches at room temperature. The reaction solution was stirred at 60° C. for 16 hours. The reaction was quenched by water, and the solution was extracted with dichloromethane (100 mL*3). The organic phase was washed with 1 M hydrochloric acid, 1 M sodium bicarbonate aqueous solution and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (eluent: 5% hexane/95% ethyl acetate) to obtain (5-nitroquinolin-8-yloxy)methyl 2-ethylbutanoate (1.4 g, yield: 14%). 1H NMR (400 MHz, CD3OD): δ 9.17-9.14 (m, 1H), 8.97-8.95 (m, 1H), 8.55 (d, J=8.8 Hz, 1H), 7.84-7.81 (m, 1H), 7.58 (d, J=8.8 Hz, 1H), 6.21 (s, 2H), 2.34-2.27 (m, 1H), 1.67-1.47 (m, 4H), 0.815 (t, J=7.2 Hz, 6H). MS calculated: 318.1; MS observed: 319.1 [M+H]+.
di-tert-butyl (5-nitroquinolin-8-yloxy)methyl phosphate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
26%
With potassium carbonate In N,N-dimethyl-formamide at 60℃;
70.1 Step 1: Preparation of di-tert-butyl (5-nitroquinoline-8-yloxy) methyl phosphate (70)
At room temperature, add potassium carbonate (1.45 g, 10.52 mmol) to nitroquinoline (1.0 g, 5.26 mmol), di-tert-butylchloromethyl phosphate (2.04 g, 7.89 mmol)N,N-dimethylformamide (17 mL) solution. The reaction solution was stirred at 60°C for 2 hours. The reaction was quenched by adding water and extracted with dichloromethane (100 mL x 3). The organic phase was washed with 1 M hydrochloric acid, 1 M aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: 5% n-hexane/95% ethyl acetate) to obtain di-tert-butyl (5-nitroquinolin-8-yloxy) methyl phosphate (570 mg, yield: 26%).
26%
With potassium carbonate In N,N-dimethyl-formamide at 60℃; Inert atmosphere;
70.1; 71.1 Step 1: Preparation of di-tert-butyl (5-nitroquinolin-8-yloxy)methyl phosphate (70)
Potassium carbonate (1.45 g, 10.52 mmol) was added to a solution of nitroxoline (1.0 g, 5.26 mmol) and di-tert-butyl chloromethyl phosphate (2.04 g, 7.89 mmol) in N,N-dimethylformamide (17 mL) at room temperature. The reaction solution was stirred at 60° C. for 2 hours. The reaction was quenched by water, and the solution was extracted with dichloromethane (100 mL*3). The organic phase was washed with 1 M hydrochloric acid, 1 M sodium bicarbonate aqueous solution and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (eluent: 5% hexane/95% ethyl acetate) to obtain di-tert-butyl (5-nitroquinolin-8-yloxy)methyl phosphate (570 mg, yield: 26%). MS[M+H]+: 413.3.
26%
With potassium carbonate In N,N-dimethyl-formamide at 60℃; Inert atmosphere;
70.1; 71.1 Step 1: Preparation of di-tert-butyl (5-nitroquinolin-8-yloxy)methyl phosphate (70)
Potassium carbonate (1.45 g, 10.52 mmol) was added to a solution of nitroxoline (1.0 g, 5.26 mmol) and di-tert-butyl chloromethyl phosphate (2.04 g, 7.89 mmol) in N,N-dimethylformamide (17 mL) at room temperature. The reaction solution was stirred at 60° C. for 2 hours. The reaction was quenched by water, and the solution was extracted with dichloromethane (100 mL*3). The organic phase was washed with 1 M hydrochloric acid, 1 M sodium bicarbonate aqueous solution and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (eluent: 5% hexane/95% ethyl acetate) to obtain di-tert-butyl (5-nitroquinolin-8-yloxy)methyl phosphate (570 mg, yield: 26%). MS[M+H]+: 413.3.
With potassium carbonate
70.a.n.d.71.1 Step 1:
Step 1: Preparation of di-tert-butyl (5-nitroquinolin-8-yloxy)methyl phosphate (70) Potassium carbonate (1.45 g, 10.52 mmol) was added to a solution of nitroxoline (1.0 g, 5.26 mmol) and di-tert-butyl chloromethyl phosphate (2.04 g, 7.89 mmol) in N,N-dimethylformamide (17 mL) at room temperature. The reaction solution was stirred at 60° C. for 2 hours. The reaction was quenched by water, and the solution was extracted with dichloromethane (100 mL*3). The organic phase was washed with 1 M hydrochloric acid, 1 M sodium bicarbonate aqueous solution and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (eluent: 5% hexane/95% ethyl acetate) to obtain di-tert-butyl (5-nitroquinolin-8-yloxy)methyl phosphate (570 mg, yield: 26%). MS[M+H]+: 413.3.