* 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.
General procedure: To a mixture of alcohol in dry DMSO (10 volume) was added 1 equiv of polymer bromide and the reaction mixture was stirred at room temperature for a given period of time (Table 1). After the completion of the reaction, the reaction mixture was filtered and the polymer bed washed with DMSO. Combined DMSO layers were quenched with ice-water mixture and extracted with ether. The ether layer was given water wash, brine wash, dried over anhydrous sodium sulphate, and concentrated to get the pure carbonyl compounds. All the products were characterized by NMR and MS analysis.
79%
With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In dimethyl sulfoxide
A solution of 0.50 g (3.5 mmol) of 8-methylquinoline (21), 1.87 g (10.5 mmol) of N-bromosuccinamide (NBS), and 50 mg (0.3 mmol) of azobisisobutyronitrile (AIBN) in dichloroethane was refluxed under argon for 30 h. The reaction mixture was diluted with 150 mL dichloromethane, washed three times with 2 N NaOH, and brine, dried (MgSO4), and concentrated. The residue was refluxed in 50 mL of water for 4 h, cooled to 25 °C, diluted with 50 mL of 2 N NaOH, and extracted three times with diethyl ether. The combined organic layer was washed with brine, dried (MgSO4), concentrated, and column chromatographed on silica gel using a gradient mixture of hexane and diethyl ether as eluant to give 0.20 g (37percent yield) of 1613 and 0.30 g (53percent yield) of 2222 as solids. Compound 22 was converted to compound 16 by treating with IBX and DMSO in 79 percent yield. Compound 16: 1H NMR δ 11.45 (s, 1 H), 9.04 (dd, J = 4.3, 1.9 Hz, 1 H), 8.32 (dd, J = 7.0, 1.6 Hz, 1 H), 8.24 (dd, J = 8.4, 1.8 Hz, 1 H), 8.08 (dd, J = 8.2, 1.6 Hz, 1 H), 7.67 (t, J = 7.6 Hz, 1 H), 7.51 (dd, J = 8.4, 4.1 Hz, 1 H); 13C NMR δ 192.8, 151.5, 147.8, 136.5, 134.4, 131.9, 129.5, 128.5, 126.4, 122.0. MS (electrospray ionization) m/z 158.0 (M+H+), 128.1.
Reference：
[1] Tetrahedron Letters, 2011, vol. 52, # 51, p. 6971 - 6973
[2] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 10, p. 3480 - 3484
[3] Angewandte Chemie - International Edition, 2016, vol. 55, # 31, p. 9084 - 9087[4] Angew. Chem., 2016, vol. 128, # 31, p. 9230 - 9233,4
2
[ 16567-18-3 ]
[ 68-12-2 ]
[ 38707-70-9 ]
Yield
Reaction Conditions
Operation in experiment
53%
With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.166667 h;
To a solution of 13a (100 mg, 0.48 mmol) in dry THF (1.5 mL) at -78 °C nBuLi (2.5 M in n-hexane, 300 μL, 0.72 mmol) was added dropwise. The resulting solution turned to red and DMF (192 μL, 2.49 mmol) was added. After 10 min at -78 °C the mixture was quenched with water. The reaction was poured into a saturated aqueous solution of NaHCO3 (10 mL) and extracted with EtOAc (3 * 10 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel (10percent EtOAc in n-hexane) to afford the title compound as a yellow solid (53percent yield). 1H NMR (CDCl3, 300 MHz) δ 11.44 (s, 1H), 9.03 (dd, J1 = 1.8 Hz, J2 = 4.2 Hz, 1H), 8.31 (dd, J1 = 1.2 Hz, J2 = 7.2 Hz, 1H), 8.23 (dd, J1 = 1.8 Hz, J2 = 8.1 Hz, 1H), 8.08 (dd, J1 = 1.5 Hz, J2 = 8.4 Hz, 1H), 7.66 (t, J = 7.8 Hz, 1H), 7.50 (dd, J1 = 4.5 Hz, J2 = 8.4 Hz, 1H); ESI-MS m/z 158 [M+H]+; 180 [M+Na]+.
Reference：
[1] European Journal of Medicinal Chemistry, 2019, p. 290 - 320
[2] Journal of Organic Chemistry, 1980, vol. 45, # 8, p. 1514 - 1515
3
[ 68-12-2 ]
[ 38707-70-9 ]
Yield
Reaction Conditions
Operation in experiment
58%
Stage #1: With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.166667 h; Stage #2: at -78℃; for 0.166667 h;
sec-Butyllithium (1.4 M in cyclohexane, 5. 0ml, 7. 0mmol) is added dropwise to a stirred solution of 8-bromoquinoline (1.29g, 6. 22mmol) and anhydrous tetrahydrofuran (22ml) at-78°C under nitrogen. The reaction is then stirred at-78°C for 10 min and then dimethylformamide (2. 5ml, 32.3mmol) is added. The reaction is then stirred for 10 min at-78°C and then quenched with water. The reaction is poured into saturated sodium bicarbonate (100ml) and extracted with ethyl acetate (100ml x3). The ethyl acetate is dried over sodium sulfate and then the sodium sulfate is filtered. The crude product is concentrated on a rotary evaporator and purified by flash chromatography on silica gel eluting with 20percent ethyl acetate/hexanes to yield (0.57g, 58percent) of quinoline-8- carboxaldehyde : mass spectrum (ion spray) : m/z=158. 0 (M+l) : 1H NMR (CDC13) : 8= 11.46 (1H, s), 9.06-9. 04 (1H, m), 8.34-8. 32 (1H, m), 8.26-8. 23 (1H, m), 8.11-8. 08 (1H, m), 7.70-7. 66 (1H, m), 7.53-7. 50 (1H, m).
Reference：
[1] Chemistry of Natural Compounds, 1982, vol. 18, p. 598 - 600[2] Khimiya Prirodnykh Soedinenii, 1982, vol. 18, # 5, p. 633 - 635
[3] Chemistry - An Asian Journal, 2016, vol. 11, # 3, p. 385 - 389
[4] Journal of the American Chemical Society, 1997, vol. 119, # 38, p. 8991 - 9001
[5] Tetrahedron, 2004, vol. 60, # 51, p. 11889 - 11894
[6] Journal of Organic Chemistry, 1957, vol. 22, p. 217
[7] Zhurnal Obshchei Khimii, 1944, vol. 14, p. 330,334[8] Chem.Abstr., 1945, p. 4076
[9] Farmaco, Edizione Scientifica, 1951, vol. 6, p. 327,330
[10] Liebigs Annalen der Chemie, 1988, p. 455 - 464
[11] Journal of Organometallic Chemistry, 1987, vol. 319, p. 257 - 264
[12] Pakistan Journal of Scientific and Industrial Research, 1993, vol. 36, # 9, p. 357 - 359
[13] Journal of Organometallic Chemistry, 1983, vol. 243, # 1, p. 101 - 110
[14] Helvetica Chimica Acta, 1954, vol. 37, p. 90,93
[15] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 10, p. 3480 - 3484
[16] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 10, p. 3480 - 3484
[17] Angewandte Chemie - International Edition, 2016, vol. 55, # 31, p. 9084 - 9087[18] Angew. Chem., 2016, vol. 128, # 31, p. 9230 - 9233,4
5
[ 86-59-9 ]
[ 38707-70-9 ]
Reference：
[1] ACS Catalysis, 2018, vol. 8, # 12, p. 11134 - 11139
[2] Journal of the Chemical Society, 1943, p. 413,416
6
[ 7496-46-0 ]
[ 38707-70-9 ]
[ 16032-35-2 ]
Yield
Reaction Conditions
Operation in experiment
0.2 g
for 4 h; Reflux
A solution of 0.50 g (3.5 mmol) of 8-methylquinoline (21), 1.87 g (10.5 mmol) of N-bromosuccinamide (NBS), and 50 mg (0.3 mmol) of azobisisobutyronitrile (AIBN) in dichloroethane was refluxed under argon for 30 h. The reaction mixture was diluted with 150 mL dichloromethane, washed three times with 2 N NaOH, and brine, dried (MgSO4), and concentrated. The residue was refluxed in 50 mL of water for 4 h, cooled to 25 °C, diluted with 50 mL of 2 N NaOH, and extracted three times with diethyl ether. The combined organic layer was washed with brine, dried (MgSO4), concentrated, and column chromatographed on silica gel using a gradient mixture of hexane and diethyl ether as eluant to give 0.20 g (37percent yield) of 1613 and 0.30 g (53percent yield) of 2222 as solids. Compound 22 was converted to compound 16 by treating with IBX and DMSO in 79 percent yield. Compound 16: 1H NMR δ 11.45 (s, 1 H), 9.04 (dd, J = 4.3, 1.9 Hz, 1 H), 8.32 (dd, J = 7.0, 1.6 Hz, 1 H), 8.24 (dd, J = 8.4, 1.8 Hz, 1 H), 8.08 (dd, J = 8.2, 1.6 Hz, 1 H), 7.67 (t, J = 7.6 Hz, 1 H), 7.51 (dd, J = 8.4, 4.1 Hz, 1 H); 13C NMR δ 192.8, 151.5, 147.8, 136.5, 134.4, 131.9, 129.5, 128.5, 126.4, 122.0. MS (electrospray ionization) m/z 158.0 (M+H+), 128.1.Compound 22: 1H NMR δ 8.77 (dd, J = 3.9, 1.2 Hz, 1 H), 8.07 (dd, J = 8.2, 1.2 Hz, 1 H), 7.65 (d, J = 8.2 Hz, 1 H), 7.55 (d, J = 7.0 Hz, 1 H), 7.40 (t, J = 7.6 Hz, 1 H), 7.32 (dd, J = 8.2, 4.3 Hz, 1 H), 5.20 (s, 2 H); 13C NMR δ 149.0, 146.8, 138.2, 136.7, 128.3, 127.5, 127.3, 126.4, 121.1, 64.2. MS (electrospray ionization) m/z 160.3 (M+H+), 142.0, 141.1.
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 10, p. 3480 - 3484
7
[ 85219-47-2 ]
[ 38707-70-9 ]
Reference：
[1] Journal of Organometallic Chemistry, 1983, vol. 243, # 1, p. 101 - 110
[2] Helvetica Chimica Acta, 1954, vol. 37, p. 90,93
8
[ 7496-46-0 ]
[ 38707-70-9 ]
Reference：
[1] Justus Liebigs Annalen der Chemie, 1913, vol. 396, p. 47
[2] Organic Preparations and Procedures International, 2003, vol. 35, # 6, p. 627 - 630
[3] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 10, p. 3480 - 3484
9
[ 615-36-1 ]
[ 38707-70-9 ]
Reference：
[1] Journal of Organic Chemistry, 1980, vol. 45, # 8, p. 1514 - 1515
[2] European Journal of Medicinal Chemistry, 2019, p. 290 - 320
10
[ 858784-66-4 ]
[ 38707-70-9 ]
Reference：
[1] Journal of the Chemical Society, 1943, p. 413,416
11
[ 79663-29-9 ]
[ 38707-70-9 ]
Reference：
[1] Angewandte Chemie - International Edition, 2016, vol. 55, # 31, p. 9084 - 9087[2] Angew. Chem., 2016, vol. 128, # 31, p. 9230 - 9233,4
12
[ 578-66-5 ]
[ 38707-70-9 ]
Reference：
[1] European Journal of Medicinal Chemistry, 2019, p. 290 - 320
13
[ 215606-70-5 ]
[ 38707-70-9 ]
Reference：
[1] Chemische Berichte, 1902, vol. 35, p. 1273
14
[ 94127-04-5 ]
[ 38707-70-9 ]
Reference：
[1] Chemische Berichte, 1902, vol. 35, p. 1273
15
[ 25635-22-7 ]
[ 38707-70-9 ]
Reference：
[1] Journal of the Chemical Society, 1943, p. 413,416
16
[ 85949-81-1 ]
[ 38707-70-9 ]
Reference：
[1] Journal of the Chemical Society, 1943, p. 413,416
17
[ 95-53-4 ]
[ 38707-70-9 ]
Reference：
[1] Farmaco, Edizione Scientifica, 1951, vol. 6, p. 327,330
18
[ 215606-70-5 ]
[ 7697-37-2 ]
[ 38707-70-9 ]
Reference：
[1] Chemische Berichte, 1902, vol. 35, p. 1273
19
[ 38707-70-9 ]
[ 86-59-9 ]
Reference：
[1] Chemische Berichte, 1902, vol. 35, p. 1273
[2] Journal of the American Chemical Society, 1951, vol. 73, p. 5622,5627
[3] Organic Preparations and Procedures International, 2003, vol. 35, # 6, p. 627 - 630
Example 113; 5-(Quinolin-8-ylmethoxy)-quinazoline-2, 4-diamine; [00327] Step 1; Sodium borohydride (280 mg, 7.4 mmol) was added in portions to a solution of 3-quinoline-carboxaldehyde (1.06 g, 6.7 mmol) in methanol at room temperature. Reaction was quenched after 3 hours stirring with 10 mL (aq) sat. NH4Cl. Mixture was extracted with ethyl acetate (3 X 30 ml). Combined organics were washed with brine and dried over MgS04. Crude material was purified by chromatography using (20-40% EA/Hex gradient) to afford quinolin-8-yl-methanol as an off white solid (800 mg; 75% yield).
With n-butyllithium; In tetrahydrofuran; hexane; at -78℃; for 0.166667h;
To a solution of 13a (100?mg, 0.48?mmol) in dry THF (1.5?mL) at -78?C nBuLi (2.5?M in n-hexane, 300?muL, 0.72?mmol) was added dropwise. The resulting solution turned to red and DMF (192?muL, 2.49?mmol) was added. After 10?min?at -78?C the mixture was quenched with water. The reaction was poured into a saturated aqueous solution of NaHCO3 (10?mL) and extracted with EtOAc (3?*?10?mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel (10% EtOAc in n-hexane) to afford the title compound as a yellow solid (53% yield). 1H NMR (CDCl3, 300?MHz) delta 11.44 (s, 1H), 9.03 (dd, J1?=?1.8?Hz, J2?=?4.2?Hz, 1H), 8.31 (dd, J1?=?1.2?Hz, J2?=?7.2?Hz, 1H), 8.23 (dd, J1?=?1.8?Hz, J2?=?8.1?Hz, 1H), 8.08 (dd, J1?=?1.5?Hz, J2?=?8.4?Hz, 1H), 7.66 (t, J?=?7.8?Hz, 1H), 7.50 (dd, J1?=?4.5?Hz, J2?=?8.4?Hz, 1H); ESI-MS m/z 158 [M+H]+; 180 [M+Na]+.
With toluene-4-sulfonic acid; In ethanol; for 1h;Heating / reflux;
b) A mixture of <strong>[38707-70-9]8-quinolinecarboxaldehyde</strong> (0.248 mol), triethoxymethane (0.4464 mol) and 4-methylbenzenesulfonic acid (4g) in ethanol (250ml) was stirred and refluxed for 1 hour, brought to room temperature, poured out into K2CO3 10% and extracted with EtOAc. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated. The product was used without further purification, yielding 48.5g (80%) of 8-(diethoxymethyl)-quinoline (interm. 29).
sec-Butyllithium (1.4 M in cyclohexane, 5. 0ml, 7. 0mmol) is added dropwise to a stirred solution of 8-bromoquinoline (1.29g, 6. 22mmol) and anhydrous tetrahydrofuran (22ml) at-78C under nitrogen. The reaction is then stirred at-78C for 10 min and then dimethylformamide (2. 5ml, 32.3mmol) is added. The reaction is then stirred for 10 min at-78C and then quenched with water. The reaction is poured into saturated sodium bicarbonate (100ml) and extracted with ethyl acetate (100ml x3). The ethyl acetate is dried over sodium sulfate and then the sodium sulfate is filtered. The crude product is concentrated on a rotary evaporator and purified by flash chromatography on silica gel eluting with 20% ethyl acetate/hexanes to yield (0.57g, 58%) of quinoline-8- carboxaldehyde : mass spectrum (ion spray) : m/z=158. 0 (M+l) : 1H NMR (CDC13) : 8= 11.46 (1H, s), 9.06-9. 04 (1H, m), 8.34-8. 32 (1H, m), 8.26-8. 23 (1H, m), 8.11-8. 08 (1H, m), 7.70-7. 66 (1H, m), 7.53-7. 50 (1H, m).
With ammonium chloride In tetrahydrofuran; hexane; n-heptane; ethyl acetate
1 Alternative Route to Prepare Compound II From N,N-diethyl-4-iodobenzamide (Compound IV)
Alternative Route to Prepare Compound II From N,N-diethyl-4-iodobenzamide (Compound IV) Compound IV (0.67 g, 2.2 mmol) was dissolved in dry THF (25 mL) and cooled to -78° C. under nitrogen. n-BuLi (1.3 mL, 1.6 M in hexane, 2.2 mmol) was added dropwise during 5 min. After further 10 min, 8-formylquinoline (0.17 g, 1.1 mmol) (8-formylquinoline was made from 8-methylquinoline by oxidation with selenium dioxide at 150-155° C. for 12 h (Kingsbury, J. Med. Chem. 1993, 3308.) was added dissolved in THE (1 mL). The solution was stirred 1 h, then NH4Cl (aq.) was added. After concentration, aqueous workup and chromatography on silica (0-100% EtOAc in heptane), a total of 0.29 g (78%) compound II was obtained.
58] Intermediate 14 301[59] A solution of 4-iodo-l-tritylimidazole (commercially available) 5.2 g, 11.94 mmol) in dichloromethane (80 mL) at -10 0C was treated with ethyl magnesium bromide (3.98 mL, 11.94 mmol, 3M in ether) and allowed to react for 45 m. A solution of <strong>[38707-70-9]quinoline-8-carbaldehyde</strong>, (Intermediate 11) (1.5 g, 9.55 mmol) in dichloromethane was added via syringe at -10 0C and stirred for 16 h at room temperature. The mixture was quenched with water (50 mL) and a sat. solution of ammonium chloride (50 mL) and subjected to an aqueous work-up. The residue was purified by chromatography on silica gel with 3% NH3-MeOH: CH2Cl2 to give to give quinolin-8-yl(l-trityl-lH-imidazol-5- yl)methanol, (Intermediate 12) as a solid, (3.7 g 82.7%).
With Br3(1-)*C10H15NPol(1+); dimethyl sulfoxide; at 20℃; for 4h;
General procedure: To a mixture of alcohol in dry DMSO (10 volume) was added 1 equiv of polymer bromide and the reaction mixture was stirred at room temperature for a given period of time (Table 1). After the completion of the reaction, the reaction mixture was filtered and the polymer bed washed with DMSO. Combined DMSO layers were quenched with ice-water mixture and extracted with ether. The ether layer was given water wash, brine wash, dried over anhydrous sodium sulphate, and concentrated to get the pure carbonyl compounds. All the products were characterized by NMR and MS analysis.
79%
With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione; In dimethyl sulfoxide;
A solution of 0.50 g (3.5 mmol) of 8-methylquinoline (21), 1.87 g (10.5 mmol) of N-bromosuccinamide (NBS), and 50 mg (0.3 mmol) of azobisisobutyronitrile (AIBN) in dichloroethane was refluxed under argon for 30 h. The reaction mixture was diluted with 150 mL dichloromethane, washed three times with 2 N NaOH, and brine, dried (MgSO4), and concentrated. The residue was refluxed in 50 mL of water for 4 h, cooled to 25 C, diluted with 50 mL of 2 N NaOH, and extracted three times with diethyl ether. The combined organic layer was washed with brine, dried (MgSO4), concentrated, and column chromatographed on silica gel using a gradient mixture of hexane and diethyl ether as eluant to give 0.20 g (37% yield) of 1613 and 0.30 g (53% yield) of 2222 as solids. Compound 22 was converted to compound 16 by treating with IBX and DMSO in 79 % yield. Compound 16: 1H NMR delta 11.45 (s, 1 H), 9.04 (dd, J = 4.3, 1.9 Hz, 1 H), 8.32 (dd, J = 7.0, 1.6 Hz, 1 H), 8.24 (dd, J = 8.4, 1.8 Hz, 1 H), 8.08 (dd, J = 8.2, 1.6 Hz, 1 H), 7.67 (t, J = 7.6 Hz, 1 H), 7.51 (dd, J = 8.4, 4.1 Hz, 1 H); 13C NMR delta 192.8, 151.5, 147.8, 136.5, 134.4, 131.9, 129.5, 128.5, 126.4, 122.0. MS (electrospray ionization) m/z 158.0 (M+H+), 128.1.
A solution of 0.50 g (3.5 mmol) of 8-methylquinoline (21), 1.87 g (10.5 mmol) of N-bromosuccinamide (NBS), and 50 mg (0.3 mmol) of azobisisobutyronitrile (AIBN) in dichloroethane was refluxed under argon for 30 h. The reaction mixture was diluted with 150 mL dichloromethane, washed three times with 2 N NaOH, and brine, dried (MgSO4), and concentrated. The residue was refluxed in 50 mL of water for 4 h, cooled to 25 °C, diluted with 50 mL of 2 N NaOH, and extracted three times with diethyl ether. The combined organic layer was washed with brine, dried (MgSO4), concentrated, and column chromatographed on silica gel using a gradient mixture of hexane and diethyl ether as eluant to give 0.20 g (37percent yield) of 1613 and 0.30 g (53percent yield) of 2222 as solids. Compound 22 was converted to compound 16 by treating with IBX and DMSO in 79 percent yield. Compound 16: 1H NMR delta 11.45 (s, 1 H), 9.04 (dd, J = 4.3, 1.9 Hz, 1 H), 8.32 (dd, J = 7.0, 1.6 Hz, 1 H), 8.24 (dd, J = 8.4, 1.8 Hz, 1 H), 8.08 (dd, J = 8.2, 1.6 Hz, 1 H), 7.67 (t, J = 7.6 Hz, 1 H), 7.51 (dd, J = 8.4, 4.1 Hz, 1 H); 13C NMR delta 192.8, 151.5, 147.8, 136.5, 134.4, 131.9, 129.5, 128.5, 126.4, 122.0. MS (electrospray ionization) m/z 158.0 (M+H+), 128.1.Compound 22: 1H NMR delta 8.77 (dd, J = 3.9, 1.2 Hz, 1 H), 8.07 (dd, J = 8.2, 1.2 Hz, 1 H), 7.65 (d, J = 8.2 Hz, 1 H), 7.55 (d, J = 7.0 Hz, 1 H), 7.40 (t, J = 7.6 Hz, 1 H), 7.32 (dd, J = 8.2, 4.3 Hz, 1 H), 5.20 (s, 2 H); 13C NMR delta 149.0, 146.8, 138.2, 136.7, 128.3, 127.5, 127.3, 126.4, 121.1, 64.2. MS (electrospray ionization) m/z 160.3 (M+H+), 142.0, 141.1.
General procedure: A mixture of the appropriate amine (1M-3M, 2 mmol) and the appropriate aldehyde (2.2 mmol) in ethanol (10 mL) was stirred at room temperature for 8 h.
With potassium tert-butylate; In dimethyl sulfoxide; at 20℃; for 2h;
General procedure: To a solution of phosphonium salt 35 (1.2 equiv) and t-BuOK (1.2 equiv) in DMSO (1 ml/mmol) was added appropriate aldehyde (1.0 equiv) and the mixture was stirred at ambient temperature until the starting aldehyde disappeared (ca. 2 h). The reaction mixture was diluted with water, the organics were extracted with CHCl3, dried (Na2SO4), concentrated, and purified by column chromatography to give compounds 36i-p and 43 as white or slightly colored solids.
General procedure: A solution of 25 mg (0.071 mmol) of 6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinolin-8-amine (17) and 9 mg (0.078 mmol) of 1,3-thiazole-2-carboxaldehyde (18) in 1 mL of methanol was stirred under argon at 25 C for 30 min. To it, 1 drop of acetic acid and 13 mg (0.213 mmol) of sodium cyanoborohydride were added, and the solution was stirred for 12 h, diluted with 30 mL of aqueous ammonium chloride solution, and extracted three times with ethyl acetate. The combined extract was washed with water, brine, dried (MgSO4), concentrated, and column chromatographed on silica gel using a mixture of hexane and diethyl ether (1:1) as an eluent to give 23 mg (72% yield) of compound 2 as a light yellow oil.
4-(2-((2,4-difluorophenyl)amino)-5-((methylsulfonyl)methyl)phenyl)-6-methyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one[ No CAS ]
4-(2,4-difluorophenyl)-10-methyl-7-((methylsulfonyl)methyl)-3-(quinolin-8-yl)-3,4-dihydro-1H-1,4,10-triazadibenzo[cd,f]azulen-11(10H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
20%
With titanium tetrachloride; In tetrahydrofuran; toluene; at 60℃; for 48h;
Example 12d (532 mg, 0.120 mmol) and qumolirifi-S-carbaldehyde (94.0 mg, 0.600 mmol) were com ined in tetrahydroturan ( l mL). To this suspensionwas added 1M titanium (IV) chloride in toluene (0.240 mL, 0.240 mmol). The reaction mixture was healed at 60 * for 4S hours, cooled, diluted withwater, the pH adjusted to 7 y the addition of saturated aqueous sodiumbicarbonate, and extracted with ethyl acetate. The organic layer was washed with s aturated aqueous s odium cliloride, dried withanl^lrous sodium sulfate, filtered, and concentrated. The residue was purified b y flas h chromatography (s ilica geL 2-4 % methanol in dichlorornethane) to provide the title compound ( 14 mg, 20 ). 1 H NMR (500 MHz, DMSO-_4) 5 12.02 (s, 1H), 9.14 (dd, J = 4.2, 1 .7 Hz. 1H), S.34 (dd, /= S.3, 1 .7 Hz, 1H), S .21 (td, = 9.6, 6.2 Hz, 1 H 7.77 - 7 J6S (m, 4H), 7J62 (dd, /= S.3, 4.2 Hz, 1H), 729 (d, = 2.1 Hz, 1 H), 7 OS (t, / = 7.7 Hz, 1 E 7.00 (td, J = S.1 , 20 Hz, 1H), 6.93 - 6.S4 (m, 2E 6.71 (dd, J = S. l , l.S Hz. 1H), 609 (d, = S .1 Hz, 1 E 4.37 - 4.23 (m, 2E 3.69 (s, 3E 2.64 (s , 3H). MuXi (EpsilonXi 1+ ) m/z 583 (M+H) 1.
3-ethyl-1-isopentyl-1,3,8-triazaspiro[4.5]decane-2,4-dione hydrochloride[ No CAS ]
3-ethyl-1-(3-methylbutyl)-8-(quinolin-8-ylmethyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione hydrochloride[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
78.7%
A mixture of 12n (100.2 mg, 0.33 mmol, 1.0 equiv) and quinolone-8-carboxaldehyde (102.9 mg, 0.655 mmol, 1.985 equiv) was dissolved in DMF (2 mL) and was stirred at room temp for 30 minutes before the addition of sodium triacetoxyborohydride (174.74mg, 0.824 mmol, 2.5 equiv). After 48 hrs, reaction was quenched with a few drops of water, followed by TFA. The solution was then purified by reverse phase HPLC (10 to 60%acetonitrile/water/0.05%TFA). Fractions were then combined and concentrated, leaving an oily yellowish product. This oil was then washed with saturated sodium bicarbonate and extracted twice with EtOAc. The organic layers were then combined, dried, filtered and concentrated to give a yellow oily product (112.4mg). This oil was then diluted with a minimal amount of diethyl ether and transferred to a 2 dram vial, along with 330 muL of HCl (1 M in diethyl ether). This mixture was slurried for ~30 minutes, then filtered and dried to give the target compound (an offwhite solid) as an HCl salt (115.5 mg, 0.260 mmol, 78.7% yield). 1H NMR (400 MHz, DMSO-d6)delta 9.06 (dd, J=4.1, 1.6 Hz, 1 H), 8.52 (dd, J=8.3, 1.7 Hz, 1 H), 8.21 (dd, J=7.1, 1.3 Hz, 1 H), 8.17 (dd, J=8.3, 1.3 Hz, 1 H), 7.75 (dd, J=8.2, 7.2 Hz, 1 H), 7.68 (dd, J=8.3, 4.2 Hz, 1 H), 5.01 (br. s.,2 H), 3.43 - 3.61 (m, 4 H), 3.32 - 3.42 (m, 2 H), 3.17 (t, J=1.0 Hz, 2 H), 2.08 (s, 2 H), 1.92 (d,J=14.7 Hz, 2 H), 1.48 - 1.59 (m, 1 H), 1.41 (d, J=7.9 Hz, 2 H), 1.04 - 1.11 (m, 3 H), 0.88 (d,J=6.4 Hz, 6 H). ES-MS m/z 410 (MH+).
4-hydroxy-6-methyl-3-[(2E)-3-quinolin-8-ylprop-2-enoyl]-2H-pyran-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
With piperidine; In chloroform;Reflux;
General procedure: A mixture of dehydroacetic acid (1.68 g; 0.01 mol) and R-carboxaldehyde(0.01 mol) were refluxed in 25 ml of chloroform containinga few drops of piperidine. 5e7 ml of the chloroform-waterazeotrope mixture was removed by a simple distillation. Theproduct were obtained by slow evaporation of the remainingchloroform and washed with ethyl acetate (2 5 ml). L3 and L4were recrystalized from dichloromethane and a mixture of Ethanoland a few drops of DMSO, respectively. Crystals were dried undervaccum.
With ammonium acetate; phenyltrimethylammonium tribromide; In acetonitrile; at 20℃; for 14h;
General procedure: to a solution of 2-pyridinecarbaldehyde 1 (54 mg, 0.5 mmol) and ammonium acetate (385mg, 5.0 mmol) in MeCN )6ml), was added trimethylphenylammonium tribromide (376 mg, 1.0 mmol) at room temperature. after stirring for 21 h at rt, the reaction mixture was treated with 0.5 M aq Na2S2O3(10 ml), 1.0 M NaHCO3 )15 ml) and extracted with EtOAc (60 mL). The organic layer was washed with 0.5 M Na2S2O3 and successively washed with saturated aq.NaCl, and dried over MgSO4.
4,4-difluoro-8-(4'-iodophenyl)-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene[ No CAS ]
C29H23BF2IN3[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
18%
With piperidine; toluene-4-sulfonic acid; In toluene; at 140℃; for 3h;Inert atmosphere; Schlenk technique; Dean-Stark;
General procedure: In a round bottom flask equipped with a Dean stark apparatus, <strong>[38707-70-9]quinoline-8-carboxaldehyde</strong> 1(2.2 equiv.), piperidine (2 ml) and acrystal of p-TsOH were added to astirred solution of the relevant BODIPY dye (1.0 equiv.) in toluene (20 ml).The mixture was heated at 140 C for 3 hours. After cooling to room temperature, the mixture was washed three times with water. The organic phase was dried over MgSO4 and the solvent was evaporated under reduced pressure. The resulting crude residue was purified by silica-gel column chromatography to afford the desired compound.
2,6-diethyl-4,4-difluoro-1,3,5,7-tetramethyl-8-(4-iodophenyl)-4-bora-3a,4a-diaza-s-indacene[ No CAS ]
C33H31BF2IN3[ No CAS ]
C43H36BF2IN4[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
53%; 27%
With piperidine; toluene-4-sulfonic acid; In toluene; at 140℃; for 3h;Inert atmosphere; Schlenk technique; Dean-Stark;
General procedure: In a round bottom flask equipped with a Dean stark apparatus, <strong>[38707-70-9]quinoline-8-carboxaldehyde</strong> 1(2.2 equiv.), piperidine (2 ml) and acrystal of p-TsOH were added to astirred solution of the relevant BODIPY dye (1.0 equiv.) in toluene (20 ml).The mixture was heated at 140 C for 3 hours. After cooling to room temperature, the mixture was washed three times with water. The organic phase was dried over MgSO4 and the solvent was evaporated under reduced pressure. The resulting crude residue was purified by silica-gel column chromatography to afford the desired compound.
With piperidine; toluene-4-sulfonic acid; In toluene; at 140℃; for 3h;Inert atmosphere; Schlenk technique; Dean-Stark;
General procedure: In a round bottom flask equipped with a Dean stark apparatus, <strong>[38707-70-9]quinoline-8-carboxaldehyde</strong> 1(2.2 equiv.), piperidine (2 ml) and acrystal of p-TsOH were added to astirred solution of the relevant BODIPY dye (1.0 equiv.) in toluene (20 ml).The mixture was heated at 140 C for 3 hours. After cooling to room temperature, the mixture was washed three times with water. The organic phase was dried over MgSO4 and the solvent was evaporated under reduced pressure. The resulting crude residue was purified by silica-gel column chromatography to afford the desired compound.
8-quinolinecarbaldehyde salicylhydrazone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
In methanol; for 6h;Reflux;
Take <strong>[38707-70-9]quinoline-8-formaldehyde</strong> 157mg and salicylaldide 152mg in a round bottom flask,Add 50 mL of methanol,The reaction was refluxed for 6 hours. After cooling to room temperature, a yellow precipitate is obtained and filtered.The filter residue was successively washed twice with methanol and ether.Dry, talk about yellow solids,Yield 90%.
General procedure: Carbohydrazones 1-7 were prepared by reactions of <strong>[497-18-7]carbohydrazide</strong> (1,3-diaminourea,10 mmol) and appropriate aldehydes and ketones (5 mmol) in water (10 ml) at room temperaturewith addition one drop of conc. hydrochloric acid. Reaction mixture was stirred for 2h and the resulting precipitate was collected by filtration, and recrystallized from a suitablesolvent
Weigh 1.225 g (1.4 mmol) Heptaisobutyl-propylamino polysilsesquioxane (C31H71NO12Si8),0.224 g (1.4 mmol) 8-aldehyde quinoline (KL),10 mL methylene chloride (CH2CI2) - Add 50 mL portions The flask was stirred at room temperature for 12 h.When solvent dichloromethane was added, the reactant solids were all dissolved and a light yellow solution.The color of the solution changed significantly after 12 h. The reaction mixture was rotary evaporated on a rotary evaporatorThe solvent was removed to give a yellow mixture solid,The mixture was then washed with 50 mL of methanol and washed repeatedly Polyester, filtered 5 times, the yield after drying was 67%. Abbreviated as P1.
N-((quinolin-8-yl)methylene)acetohydrazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90.6%
In ethanol; at 20℃; under 760.051 Torr; for 5h;
1.57 g of <strong>[38707-70-9]quinoline-8-carbaldehyde</strong> was dissolved in 50 mL of absolute ethanol,An additional 0.94 g of acetohydrazide,The reaction was stirred at room temperature and pressure 5h,Precipitation of a large number of solids,Vacuum filtration,The residue was washed with anhydrous ethanol to give a white solid as the target product,The yield of the target product was 90.6%.
62%
In ethanol; at 20℃; for 0.5h;
As shown in Scheme 1, a mixture of <strong>[38707-70-9]8-formylquinoline</strong> (1.57g, 10mmol) and acethydrazide (0.74g, 10mmol) in ethanol (30ml) were stirred at room temperature for 0.5h, clear brown solution was formed. The pale-yellow solid was precipitated after stirring for another 4h, then filtered and washed three times with ethanol. Yield: 1.32g (62%). M.p.: 168-170C. Elemental analysis for HL (C12H11N3O) (%): Calc.: C: 67.59; H: 5.20; N: 19.71; Found: C: 67.48; H: 5.27; N: 19.64. FT-IR (cm-1): v(C=O) 1673, v(C=N, imine) 1615, v(C=N, quinoline) 1584. 1H NMR (400MHz, d6-DMSO) delta:11.69/11.45 (1H, s, 1:2, OH/NH), 9.45/9.28 (1H, s, 1:2, H10), 8.97-8.99 (1H, m, H1)/8.42-8.46 (1H, m, H7)/8.30-8.33 (1H, m, H3)/8.05-8.08 (1H, m, H5)/7.67-7.72 (1H, m, H6)/7.60-7.64 (1H, m, H2) for Ar-H, 2.28/1.99 (3H, s, 2:1, H12). 13C NMR (400MHz, d6-DMSO) delta: 172.58/166.01 (C11), 150.83/150.80 (C1), 145.74/145.65 (C9), 143.00/140.11 (C10), 137.15/137.10 (C3), 131.71/131.59 (C8), 130.31/130.08 (C5), 128.49 (C7), 127.01/126.98 (C4), 125.93/125.55 (C6), 122.35 (C2), 22.13/20.87 (C12). ESI-MS: m/z=214.0990 for [M+H]+.
8.82 g of <strong>[38707-70-9]quinoline-8-carbaldehyde</strong> was dissolved in 160 mL of 75% ethanol.Then add 2.75g of carbon dihydrazide,Under normal pressure, reflux and stir for 4h. After cooling to room temperature, a large amount of solids precipitated and was filtered under reduced pressure.The filter residue was washed with 75% ethanol to give a pale green solid, which was the target product.The yield of the target product is 85%.
(Z)-2-(1H-indol-3-yl)-3-(quinolin-8-yl)acrylonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
54%
General procedure: To an indole-3-acetonitrile derivative (1.0 equiv) dissolved in anhydrous methanol (4mL for 2.31mmol of starting material) in a dried microwave vial, sodium methoxide (1.7 equiv) was added and stirred at room temperature for 15min protected from light. Quinoline/isoquinoline-carboxaldehyde derivative (1.2 equiv) was added and the mixture was subjected to microwave irradiation at 95C for 8.5min. The reaction was cooled to room temperature and then chilled in an ice/salt bath. The resulting precipitate was filtered, washed with methanol, and dried under vacuum to afford a solid as the product.
(9-ethyl-9H-carbazol-3-yl)(quinolin-8-yl)methanol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
46.4%
To an oven-dried round-bottom flask flushed with N2 was added 3-bromo-9-ethyl-9H-carbazole (508mg, 1.85mmol) in 13mL dry THF. The mixture was cooled to-78 C and tert-BuLi (2M in heptane) (1.85mL, 3.7mmol) was added dropwise. The mixture was stirred at-78 C for 1h, then 8-Quinolinecarboxaldehyde (291mg, 1.85mmol) was added. The resulting mixture was stirred at-78 C for 1.5h, then allowed to warm to 0 C .50mL sat. N H4Cl was added, then organics were extracted with EtOAc (2×30mL), washed with water and brine, and dried over MgSO4. Solvents were removed in vacuo, and the resulting oil was purified by column chromatography eluting with a gradient of 12-100% EtOAc in Heptane to yield the title compound as a dark purple oil (303mg, 46.4% yield). 1H NMR (400MHz, Chloroform-d) delta 8.90 (dd, J=4.3, 1.8Hz, 1H), 8.26-8.24 (m, 1H), 8.22 (dd, J=8.4, 1.8Hz, 1H), 8.06 (dt, J=7.8, 1.0Hz, 1H), 7.75 (dd, J=8.0, 1.7Hz, 1H), 7.60 (dd, J=8.4, 1.7Hz, 1H), 7.45 (dd, J=6.1, 1.8Hz, 2H), 7.39 (d, J=5.0Hz, 1H), 7.19 (ddd, J=7.9, 6.9, 1.2Hz, 1H), 6.97 (s, 1H), 6.67 (s, 1H), 4.36 (q, J=7.2Hz, 2H), 1.42 (t, J=7.2Hz, 3H).
46.4%
To an oven-dried round-bottom flask flushed with N2 was added 3-bromo-9-ethyl-9/-/- carbazole (508 mg, 1.85 mmol) in 13 mL dry tetrahydrofuran. The mixture was cooled to -78 C and tert- BuLi (2M in heptane) (1.85 mL, 3.7 mmol) was added dropwise. The mixture was stirred at -78 C for 1 hour, then 8-Quinolinecarboxaldehyde (291 mg, 1.85 mmol) was added. The resulting mixture was stirred at -78 C for 1.5 hour, then allowed to warm to 0 C. 50 mL sat. NH4CI was added, then organics were extracted with ethyl acetate (2 c 30 mL), washed with water and brine, and dried over MgS04. Solvents were removed in vacuo, and the resulting oil was purified by column chromatography eluting with a gradient of 12- 100% ethyl acetate in heptane to yield the title compound as a dark purple oil (303 mg, 46.4% yield). 1 H NMR (400 MHz, CDCI3) d 8.90 (dd, J = 4.3, 1.8 Hz, 1 H), 8.26 - 8.24 (m,1 H), 8.22 (dd, J = 8.4, 1.8 Hz, 1 H), 8.06 (dt, J = 7.8, 1.0 Hz, 1 H), 7.75 (dd, J = 8.0, 1.7 Hz, 1 H), 7.60 (dd, J = 8.4, 1.7 Hz, 1 H), 7.45 (dd, J = 6.1 , 1.8 Hz, 2H), 7.39 (d, J = 5.0 Hz, 1 H), 7.19 (ddd, J = 7.9, 6.9, 1.2 Hz, 1 H), 6.97 (s, 1 H), 6.67 (s, 1 H), 4.36 (q, J = 7.2 Hz, 2H), 1.42 (t, J = 7.2 Hz, 3H).
(E)-N,N-dimethyl-2-(quinolin-8-ylmethylene)hydrazinecarbothio-amide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
69%
In methanol; at 65℃; for 2h;
By <strong>[38707-70-9]quinoline-8-formaldehyde</strong> (0.78g, 5mmol)With N,N-dimethyl-indole thiocarboxamide (0.59 g, 5 mmol)The HL ligand was prepared by condensation in methanol (50 mL).The mixed solution was heated under reflux at 65 C for 2 hours.A yellow solution was obtained.Colorless luster crystals were obtained by slowly evaporating the solution at 4 C.The yield was 0.89 g (69%).
benzyl 6‑methyl‑2‑oxo‑4‑(quinolin‑8‑yl)‑3,4‑dihydropyrimidine‑5‑carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
With 1,3,5-trichloro-2,4,6-triazine; water; In neat (no solvent); at 60℃; for 0.25h;Sonication; Green chemistry;
General procedure: A mixture of aldehyde (5 mmol), urea (6 mmol), ethyl/benzyl acetoacetate (5 mmol) and TCT (10 mol%) was mixed thoroughly in a petri dish at room temperature.Then the reaction mixture was irradiated in the ultrasonicbath at 60 C in open air for the time specified in Table 2. After completion of the reaction (monitored by TLC), the residue obtained was washed with water (4 × 25 ml) and then filtered. The formed solid was collected, dried and recrystallized from ethanol which afforded the desired 3,4-dihydropyrimidin-2(1H)-ones in excellent purity forfurther characterizations.
(S)-4-methyl-N-(quinolin-8-ylmethylene)benzenesulfinamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
81%
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 20℃; for 6h;
General procedure: In a round-bottom flask, to aldehyde (1.0 mmol) in DMF(1 mL) was added sulfinamide (2 or 2a) (1.5 mmol) followed by DBU (1.5 mmol). The solution was allowed to stirat room temperature for 2-10 h. The progress of the reaction was monitored by TLC. After complete conversion, the reaction mixture was diluted with ethyl acetate and washed with water. The organic layer was dried over anhydrous sodium sulfate, filtered, and evaporated. The crude product was subjected to column chromatography on silica gel (eluent:petroleum ether/ethyl acetate = 80:20) to provide the corresponding N-sulfinyl imines.
(S)-2-methyl-N-(quinolin-8-ylmethylene)propane-2-sulfinamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 20℃; for 5h;
General procedure: In a round-bottom flask, to aldehyde (1.0 mmol) in DMF(1 mL) was added sulfinamide (2 or 2a) (1.5 mmol) followed by DBU (1.5 mmol). The solution was allowed to stirat room temperature for 2-10 h. The progress of the reaction was monitored by TLC. After complete conversion, the reaction mixture was diluted with ethyl acetate and washed with water. The organic layer was dried over anhydrous sodium sulfate, filtered, and evaporated. The crude product was subjected to column chromatography on silica gel (eluent:petroleum ether/ethyl acetate = 80:20) to provide the corresponding N-sulfinyl imines.
8-quinolinylmethylene-4-cyclohexyl-4-methyl-3-thiosemicarbazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
88.3%
With hydrogenchloride; In ethanol; water; at 80℃; for 4h;
1) In the present invention, 1 mmol of 8-quinoline formaldehyde (0.157 g) is dissolved in 20 ml of ethanol (the concentration of the solvent ethanol is 20 v / v%), and stirred at 80 for 15 min.A solution was prepared, and the above solution was added dropwise to 20 ml of ethanol (the concentration of the solvent ethanol was 20 v / v%) with 1 mmol of 4-cyclohexyl-4-methyl-3-thiosemicarbazide (0.187 g) added. ) Add 3 drops of concentrated hydrochloric acid dropwise to the solution. After refluxing and stirring at 80 for 4 hours, a light yellow precipitate is obtained.The light yellow precipitate obtained above was filtered and washed with absolute ethanol and ether three times,After drying, the ligand 8-quinoline formaldehyde 4-cyclohexyl-4-methyl-3-thiosemicarbazide hydrochloride is obtained.After recrystallization from ethanol, light yellow crystals were obtained to obtain 8-quinoline formaldehyde 4-cyclohexyl-4-methyl-3-thiosemicarbazide ligand. The yield is 88.3%.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
