* 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.
The solution of quinoline-3-carboxylic acid (3 g, 17.32 mmol) in methanol (30 mL) was cooled on ice bath at 0°C.Then thionyl chloride (1.264 mL, 17.32 mmol) was added and the reaction mixture was heated to 80°C and maintained overnight. Reaction was monitored by TLC. After completion of reaction methanol was evaporated under reduced pressure and the resultant residue was basified with saturated sodium bicarbonate to make pH (7 to 8) to get white solid which was filtered and dried to get methyl quinoline-3- carboxylate (3.2 g, yield-99percent) as a white solid; m/z-187.3.
89%
at 0℃; for 30 h; Reflux
Quinoline-3-carboxylic acid (8 g, 46.2 mmol) was dissolved in methanol (900 mL), after which thionyl chloride (5 mL, 68.5 mmol)was added at 0 oC. The solution was kept at reflux, under stirring (10 h), monitoring the reaction progress by TLC (dichloromethane/methanol 9:1). An additional amount of thionyl chloride (5 mL) was added and the solution was kept at reflux (20 h). After cooling at room temperature, the solvent was evaporated at reduced pressure. To the residue water (400 mL) and 1 M sodium hydroxide (until pH 8) were added; the mixture was extracted with dichloromethane (4 x 400 mL). The collected organic phases were dried over sodium sulfate; after filtration, the solvent was removed at reduced pressure, to afford title compound 4 (7.78 g, 89percent), which was used directly in the next step without any further purification. The chemical and physical properties were in agreement with the reported ones.22
89%
at 0℃; for 30 h; Reflux
Quinoline-3-carboxylic acid (8 g, 46.2 mmol) was dissolved in methanol (900 mL); thionyl chloride (5 mL, 68.5 mmol) was added at 0° C. The solution was kept at reflux, under stirring (10 h), monitoring the reaction progress by TLC (dichloromethane/methanol 9:1). An additional amount of thionyl chloride (5 mL) was added and the solution was kept at reflux (20 h). After cooling at room temperature, the solvent was evaporated at reduced pressure. To the residue, water (400 ml) and 1M sodium hydroxide (until pH 8) were added; the mixture was extracted with dichloromethane (4*400 mL). The collected organic phases were dried over sodium sulfate; after filtration, the solvent was removed at reduced pressure, affording title compound 4 (7.78 g, 89percent) directly used in the next step without any further purification.
75%
Reflux
General procedure: To a suspension of the appropriate acid 17a-c (1 eq,) in MeOH (1.9 ml*mmol/eq) was added 1, 25 M HCl in MeOH solution (1.9 ml*mmol/eq). The solution was refluxed overnight, then cooled to room temperature and concentrated under vacuum. The residue was partitioned between sat. aq. NaHCO3 solution (30 ml) and EtOAc (3x35 ml). The combined organic extracts were washed with sat. aq. NaHCO3 solution (25 ml) and water (30 ml), dried over MgSO4 and concentrated under vacuum to give the pure title compounds.
74%
Reflux
Compound 3-Quinolinecarboxylic Acid (0801-131) (1.0 g, 5.78 mmol, 1.0 eq.)Dissolved in 30 ml of methanol,Then add sulfuric acid (0.5 ml),The reaction was refluxed overnight.After the reaction is completed, pH is adjusted to 8 by adding sodium bicarbonate solution.Dichloromethane extraction, liquid separation, the organic phase was dried over anhydrous sodium sulfate, spin-dry to give the product methyl 3-quinolinecarboxylate (800 mg,74percent).
61%
Stage #1: at 80℃; Stage #2: for 8 h; Reflux
Quinoline-3-carboxylic acid (0.245 g, 1 .41 mmol) was charged in the flask with stir bar and thionyl chloride was added. The resulting mixture was allowed to stir at 80 °C overnight. Upon completion, the reaction mixture was cooled to room temperature and concentrated in vacuo. MeOH was added to this crude mixture and was heated under reflux for 8 h. Upon completion, the reaction mixture was cooled to room temperature, diluted with DCM, and was washed with saturated aqueous NaHCO3. The aqueous layer was extracted with DCM twice, and the combined organic layers were dried with anhydrous Na2504. After removal of the solvents, the residue was purified by column chromatography on silica gel using EtOAc hexanes (1:6) as the eluentto give 4k (0.161 g, 61percent). 1H NMR (600 MHz,CDCI3): O 9.46 (d, J= 2.1 Hz, 1H), 8.86 (d, J= 2.2 Hz, 1H), 8.17 (d, J= 8.5 Hz, 1H), 7.95 (d, J= 8.2 Hz, 1H), 7.84 (ddd, J= 8.5, 6.9, 1.4 Hz, 1H), 7.63 (ddd, J= 8.1, 6.9, 1.2 Hz, 1H), 4.03 (5, 3H). 1H NMR matches previously reported data8.
Reference：
[1] Patent: WO2014/33604, 2014, A1, . Location in patent: Page/Page column 48
[2] Organic and Biomolecular Chemistry, 2016, vol. 14, # 24, p. 5505 - 5510
[3] Tetrahedron Asymmetry, 2013, vol. 24, # 18, p. 1142 - 1147
[4] Patent: US2016/122303, 2016, A1, . Location in patent: Paragraph 0078
[5] Tetrahedron Asymmetry, 2010, vol. 21, # 18, p. 2307 - 2313
[6] Journal of Medicinal Chemistry, 2010, vol. 53, # 3, p. 1281 - 1287
[7] European Journal of Medicinal Chemistry, 2018, vol. 149, p. 56 - 68
[8] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 15, p. 4179 - 4188
[9] Patent: CN107383024, 2017, A, . Location in patent: Paragraph 0377
[10] Patent: WO2018/152107, 2018, A1, . Location in patent: Page/Page column 19
[11] Journal of Medicinal Chemistry, 1982, vol. 25, # 9, p. 1081 - 1091
[12] Journal of Organic Chemistry, 1945, vol. 10, p. 76,85
[13] Canadian Journal of Chemistry, 1984, vol. 62, p. 1301 - 1307
[14] Phytochemistry (Elsevier), 1984, vol. 23, # 6, p. 1225 - 1228
[15] Patent: WO2017/11323, 2017, A1, . Location in patent: Paragraph 00343
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 18, p. 5532 - 5535
10
[ 34846-64-5 ]
[ 6480-68-8 ]
Reference：
[1] Tetrahedron Letters, 1995, vol. 36, # 52, p. 9561 - 9564
[2] Journal of the Chemical Society - Perkin Transactions 1, 1997, # 8, p. 1099 - 1104
[3] Journal of the American Chemical Society, 1941, vol. 63, p. 1553,1554
[4] Journal of the American Chemical Society, 1941, vol. 63, p. 1553,1554
[5] Bulletin of the Chemical Society of Japan, 1987, vol. 60, # 8, p. 2891 - 2898
The solution of quinoline-3-carboxylic acid (3 g, 17.32 mmol) in methanol (30 mL) was cooled on ice bath at 0C.Then thionyl chloride (1.264 mL, 17.32 mmol) was added and the reaction mixture was heated to 80C and maintained overnight. Reaction was monitored by TLC. After completion of reaction methanol was evaporated under reduced pressure and the resultant residue was basified with saturated sodium bicarbonate to make pH (7 to 8) to get white solid which was filtered and dried to get methyl quinoline-3- carboxylate (3.2 g, yield-99%) as a white solid; m/z-187.3.
97%
With thionyl chloride; at 0℃; for 24h;Reflux; Inert atmosphere;
To a precooled (0 C) solution of quinoline-3-carboxylic acid (1.50 g, 8.66 mmol) in MeOH (43 mL) under N2 atmosphere was added dropwise thionyl chloride (1.3 mL, 17 mmol). The resulting mixture was heated to reflux and stirred for 24 h, then allowed to cool to room temperature and concentrated in vacuo. The resulting residue was taken up in CH2Cl2 and quenched with sat. aq. NaHCO3. The layers were separated, and the aqueous phase was extracted with CH2Cl2 (3x). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to afford the product as an off-white solid (1.58 g, 97% yield). See, Chen, Org. Biomol. Chem.2016, 14 (24), 5505-5510. 1H NMR (500 MHz, Chloroform-d) d 9.43 (s, 1H), 8.82 (d, J = 2.0 Hz, 1H), 8.16 (d, J = 8.5 Hz, 1H), 7.94- 7.86 (m, 1H), 7.81 (ddd, J = 8.4, 6.9, 1.4 Hz, 1H), 7.60 (t, J = 7.5 Hz, 1H), 3.99 (s, 3H); 13C NMR (126 MHz, CDCl3) d 165.78, 149.83, 149.57, 139.07, 132.08, 129.33, 129.20, 127.64, 126.95, 123.12, 77.16, 52.59; IR (ATR) vmax 3509, 2994, 1714, 1618, 1572, 1497, 1434, 1367, 1290, 1241, 1192, 1100 cm-1; AMM 188.0704 (ESI) m/z [calc for C11H10NO2 (M+H)+ 188.0712].
89%
With thionyl chloride; at 0℃; for 30h;Reflux;
Quinoline-3-carboxylic acid (8 g, 46.2 mmol) was dissolved in methanol (900 mL), after which thionyl chloride (5 mL, 68.5 mmol)was added at 0 oC. The solution was kept at reflux, under stirring (10 h), monitoring the reaction progress by TLC (dichloromethane/methanol 9:1). An additional amount of thionyl chloride (5 mL) was added and the solution was kept at reflux (20 h). After cooling at room temperature, the solvent was evaporated at reduced pressure. To the residue water (400 mL) and 1 M sodium hydroxide (until pH 8) were added; the mixture was extracted with dichloromethane (4 x 400 mL). The collected organic phases were dried over sodium sulfate; after filtration, the solvent was removed at reduced pressure, to afford title compound 4 (7.78 g, 89%), which was used directly in the next step without any further purification. The chemical and physical properties were in agreement with the reported ones.22
89%
With thionyl chloride; at 0℃; for 30h;Reflux;
Quinoline-3-carboxylic acid (8 g, 46.2 mmol) was dissolved in methanol (900 mL); thionyl chloride (5 mL, 68.5 mmol) was added at 0 C. The solution was kept at reflux, under stirring (10 h), monitoring the reaction progress by TLC (dichloromethane/methanol 9:1). An additional amount of thionyl chloride (5 mL) was added and the solution was kept at reflux (20 h). After cooling at room temperature, the solvent was evaporated at reduced pressure. To the residue, water (400 ml) and 1M sodium hydroxide (until pH 8) were added; the mixture was extracted with dichloromethane (4*400 mL). The collected organic phases were dried over sodium sulfate; after filtration, the solvent was removed at reduced pressure, affording title compound 4 (7.78 g, 89%) directly used in the next step without any further purification.
75%
With hydrogenchloride;Reflux;
General procedure: To a suspension of the appropriate acid 17a-c (1 eq,) in MeOH (1.9 ml*mmol/eq) was added 1, 25 M HCl in MeOH solution (1.9 ml*mmol/eq). The solution was refluxed overnight, then cooled to room temperature and concentrated under vacuum. The residue was partitioned between sat. aq. NaHCO3 solution (30 ml) and EtOAc (3x35 ml). The combined organic extracts were washed with sat. aq. NaHCO3 solution (25 ml) and water (30 ml), dried over MgSO4 and concentrated under vacuum to give the pure title compounds.
74%
With sulfuric acid;Reflux;
Compound 3-Quinolinecarboxylic Acid (0801-131) (1.0 g, 5.78 mmol, 1.0 eq.)Dissolved in 30 ml of methanol,Then add sulfuric acid (0.5 ml),The reaction was refluxed overnight.After the reaction is completed, pH is adjusted to 8 by adding sodium bicarbonate solution.Dichloromethane extraction, liquid separation, the organic phase was dried over anhydrous sodium sulfate, spin-dry to give the product methyl 3-quinolinecarboxylate (800 mg,74%).
61%
Quinoline-3-carboxylic acid (0.245 g, 1 .41 mmol) was charged in the flask with stir bar and thionyl chloride was added. The resulting mixture was allowed to stir at 80 C overnight. Upon completion, the reaction mixture was cooled to room temperature and concentrated in vacuo. MeOH was added to this crude mixture and was heated under reflux for 8 h. Upon completion, the reaction mixture was cooled to room temperature, diluted with DCM, and was washed with saturated aqueous NaHCO3. The aqueous layer was extracted with DCM twice, and the combined organic layers were dried with anhydrous Na2504. After removal of the solvents, the residue was purified by column chromatography on silica gel using EtOAc hexanes (1:6) as the eluentto give 4k (0.161 g, 61%). 1H NMR (600 MHz,CDCI3): O 9.46 (d, J= 2.1 Hz, 1H), 8.86 (d, J= 2.2 Hz, 1H), 8.17 (d, J= 8.5 Hz, 1H), 7.95 (d, J= 8.2 Hz, 1H), 7.84 (ddd, J= 8.5, 6.9, 1.4 Hz, 1H), 7.63 (ddd, J= 8.1, 6.9, 1.2 Hz, 1H), 4.03 (5, 3H). 1H NMR matches previously reported data8.
With thionyl chloride; at 0℃;Reflux;
As depicted in Scheme 4-1, quinoline-3-carboxylic acid 3 was esterified with thionyl chloride in methanol to yield ester 4. Reduction of the pyridine ring of 4 with pyridine-borane complex in glacial acetic acid then delivered racemic THQ 5 whose methyl ester was saponified to yield ±-6. Alternatively, sulfonylation of ±-5 furnished compounds ±-7, which were also saponified with lithium hydroxide to afford the 3-carboxy target compounds ±-8. Further elaboration of the phenylsulfonyl group in ±-7c was accomplished by an SNAr reaction with 4- chloro-3,5-dimethylphenol followed by ester hydrolysis to afford compound ±-2, as shown in Scheme 4-2. In addition, the phenylsulfonyl moiety in ±-2 was replaced with a more flexible propylene group through a reductive amination-saponification sequence to yield ±-11.
To a stirred solution of quinoline-3-carboxylic acid (20 g, 0.12 mol) in EtOH (500 mL) was added sulfurous dichloride (25.6 mL, 0.36 mol) at room temperature. The mixture was stirred at 80 for 4 hours. The reaction was concentrated under reduced pressure. The residue was dissolved into EA (500 mL) . The organic phase was washed with saturated NaHCO3aqueous solution and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue (yellow solid, 22g, 96) was used into next step directly.1H NMR (400 MHz, DMSO-d6) delta 9.32 (s, 1H) , 8.99 (s, 1H) , 8.22 (d, J8.4 Hz, 1H) , 8.13 (d, J8.4 Hz, 1H) , 7.94 (t, J 7.6 Hz, 1H) , 7.74 (t, J7.6 Hz, 1H) , 4.44 (q, J7.2 Hz, 2H) , 1.41 (t, J7.2 Hz, 3H) ppm. MS: M/e 202 (M+1)+
Quinoline-3-carboxylic acid ((S)-2-{4-[(3S,5S)-1-((S)-1-acetyl-pyrrolidine-2-carbonyl)-5-((S)-2-dimethylcarbamoyl-pyrrolidine-1-carbonyl)-pyrrolidin-3-yloxy]-phenyl}-1-carbamoyl-ethyl)-amide[ No CAS ]
Step 1: Quinoline-3-carboxylic acid methyl ester. To a stirred solution, of quinoline-3-carboxylic acid (346 mg, 2 mmol) dissolved in 4:1 THF:MeOH (6 mL) at 0 C. was added TMS-diazomethane (2in hexane) portionwise until a diazomethane yellow color persisted. The reaction was concentrated to the give the methyl ester as a tan solid (244 mg, 65%). 1H-NMR (400 MHz, CDCl3) delta9.44 (s, 1H), 8.85 (s, 1 H), 8.17 (d, 1H), 7.96 (d, 11H), 7.84 (dd, 1H), 7.62 (dd, 11H), 4.02 (s, 3H)
With thionyl chloride; In methanol; at 0 - 80℃; for 14h;
Compound 16-a (1.00 g, 5.77 mmol, 1.00 eq) was dissolved in methanol (15.00 mL), and thionyl chloride (2.06 g, 17.31 mmol, 1.26 mL, 3.00 eq) was added thereto at 0C. The above reaction solution was stirred at 80C for 14 hours. After the reaction was completed, the reaction solution was spin-dried, to give the product of compound 16-b (1.00 g, crude), which was used directly in the next step without purification. 1H NMR (400 MHz, methanol) delta =9.82 (s, 1H), 9.72 (s, 1H), 8.52-8.58 (m, 1H), 8.30-8.42 (m, 2H), 8.05-8.14 (m, 1H), 4.13 (s, 3H).
With platinum(IV) oxide; hydrogen In trifluoroacetic acid for 46.5h;
Compound 162 Preparation of Compound 162, 5,6,7,8-tetrahydroquinoline-3-carboxylic acid
Preparation of Compound 162, 5,6,7,8-tetrahydroquinoline-3-carboxylic acid[00218] To a stirring solution of 3-quinoline carboxylic acid (500 mg, 2.89 mmol) in trifluoroacetic acid (5.80 mL) was added Adam's catalyst (58 mg, 0.255 mmol). The reaction mixture was purged with hydrogen (3 x vacuum/hydrogen cycles) and left to stir for 24 h. Further Adam's catalyst (58 mg, 0.255 mmol) was added and the reaction was allowed to stir for 22.5 h. The reaction mixture was filtered through celite and the celite pad washed with DCM. The organic solvents were removed in vacuo to afford a dark yellow oil. The oil was triturated with diethyl ether to afford a precipitate that was collected by filtration and dried under vacuum to afford the title compound as an off-white solid (323 mg, 63%).1H NMR (500 MHz, DMSO-d6) δ 8.86 (d, J = 1 .9 Hz, 2H), 8.13 (s, 1 H), 2.93 (t, J = 6.4 Hz, 2H), 2.84 (t, J = 6.2 Hz, 2H), 1 .88 - 1 .82 (m, 2H), 1 .81 - 1 .70 (m, 3H). HRMS (ESI+): calcd for C10H12NO2 (M + H)+, 178.0868; found 178.0874.
In trifluoroacetic acid
R.6.B.iv (iv)
(iv) 5,6,7,8-tetrahydroquinoline-3-carboxylic acid A mixture of 3-quinolinecarboxylic acid (1.73 g, 10.0 mmol) in trifluoroacetic acid (20 ml) with platinum dioxide (200 mg) was shaken in a Parr vessel at 10-15 psi. After 90 minutes the reaction mixture was filtered and the solvent removed in vacuo to yield an oil. The oil was added dropwise onto diethyl ether yielding a white solid which was collected by filtration and then recrystallized from ethyl acetate/hexane to yield the title compound as a white solid (770 mg).
With 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride In methanol; N,N-dimethyl-formamide at 20℃; for 24h;
3.6.1. Methyl 4-[(3-quinolinylcarbonyl)amino]benzoate 19a
Quinoline 3-carboxylic acid (0.20 g, 1.15 mmol) was dissolved in methanol (5 mL) and DMF (1 mL); methyl 4-aminobenzoate (0.17 g, 1.15 mmol) was then added followed by DMT-MM (0.30 g, 1.15 mmol). The mixture was then stirred at room temperature for 24 h. During this time the product formed as a white precipitate which was collected by filtration and dried under reduced pressure (0.25 g, 70%), m.p. >230 °C (lit. >230 °C) refPreviewPlaceHolder[2], νmax (KBr): 3249, 2994, 1715, 1676, 1600, 1478 cm-1δH (DMSO-d6): 10.9 (1H, s, NH), 9.36 (1H, d, J = 2.3, CH Ar), 8.9 (1H, d, J = 1.9, CH Ar), 8.12-8.17 (2H, m, CH Ar), 7.99-8.02 (4H, m, CH Ar), 7.89-7.91 (1H, m, C12), 7.74 (1H, t, J = 7.5, C13), 3.85 (3H, s, CH3). HREIMS: found 306.1007; C18H14N2O3 requires 306.1004.
49%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h;
With 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride In methanol; N,N-dimethyl-formamide at 20℃; for 24h;
quinoline-3-carboxylic acid (1,1-dioxo-1H-1λ6-benzo[b]thiophen-6-yl)amide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
48%
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 96h;
General procedure: [00160] To a solution of pyridine-2-carboxylic acid (148 mg, 1.2 mmol) and1,1-dioxo-1H-IA6-benzo[b]thiophen-6-ylamine (181 mg, 1.0 mmol) in 10 mL of DCM wasadded DIPEA (388 mg, 3.0 mmol). HBTU (570 mg, 1.5 mmol) was added at 0 C. Theresulting mixture was stirred at r. t. for 24 h and then was concentrated. The residue wasdissolved in DMF (10 mL). The solution was added to the stirring water (50 mL) dropwise. Ayellow solid was formed. The solid was filtered and washed with H20 (50 mL). 130 mg ofthe desired product was obtained as a yellow solid (45% yield). The general procedure was the same as HJC-3-20 by using quinoline-3-carboxylic acid as reactant. Obtained as a pale yellow solid (48% yield); 1H NMR (600MHz, DMSO-d6) o 11.25 (s, 1H), 9.08 (d, 1H, J= 4.2 Hz), 8.31 (s, 1H), 8.18 (d, 1H, J= 8.4Hz), 8.14 (d, 1H, J= 7.2 Hz), 7.93-7.95 (m, 1H), 7.85-7.88 (m, 1H), 7.79 (d, 1H, J= 4.2 Hz),7.70-7.72 (m, 1H), 7.63-7.65 (m, 2H), 7.34 (d, 1H, J= 6.6 Hz). 13C NMR (150 MHz, DMSOd6)0 166.7, 151.0, 149.7, 142.4, 139.1, 133.1, 131.6, 130.7, 128.5, 127.7, 127.2, 126.3,125.1, 124.8, 124.7, 120.0, 113.3, 113.2.
tert-butyl 6-(quinoline-3-carboxamido)indoline-1-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
68%
Stage #1: quinoline-3-carboxylic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere;
Stage #2: 6-amino-2,3-dihydroindole-1-carboxylic acid tert-butyl ester With triethylamine In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere;
Stage #1: quinoline-3-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 1h;
Stage #2: L-serine isopropyl ester hydrochloride With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 70℃; for 6h;
4.10. General procedure for the synthesis of compounds (12a-t)
General procedure: To a solution of the intermediate acid compound 1a-f (1 equiv.)in anhydrous DMF was added EDCI (1.1 equiv) and HOBt (1.1equiv), respectively. The reaction mixture was stirred for 1 h at ambient temperature, and the L-serine ester (1.1 equiv.) and DIEA(3 equiv.) were added. The solution was heated to 70 C for 6 hand then cooled to room temperature. The reaction mixture was poured into ice water, and the resulting solid was filtered and dried to give the desired compound.
N,N′-(decane-1,10-diyl)bis(quinoline-3-carboxamide)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
59%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 12h;
In a round bottom flask, 0.400 g of quinoline-3-carboxylic acid, 0.181 g of decanediamine, 0.443 g of EDCI, 0.026 g of DMAP, and 10 mL of anhydrous dichloromethane were successively added, and the mixture was stirred at room temperature for 12 hours. A white solid was isolated, suction filtered, washed sequentially with dichloromethane (2× 2.5 mL) and water (3×5 mL).Dry to give a white solid 0.300 g,The yield was 59% (see Figure 19 for the synthetic route and Figure 20 for the characterization map).
59%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 12h;
General procedure: Compounds 9e-35e were obtained by using one-pot reaction. A mixture of aromatic acid (6.30 mmol), EDCI (7.50 mmol), DMAP (0.60 mmol), and anhydrous dichloromethane (20 mL) was stirred to dissolve, then decane-diamine (3 mmol) was added and stirred at room temperature for 12 h. The mixture solution was filtered under reduced pressure. After that, the residue was washed with little amount of CH2Cl2and water successively, and dried to give the solid. Then, the residue was purified on preparative TLC eluted with chloroform/methanol = 40:1-7:1 to yield compounds 26e, 28e, 30e, and 31e.
In 1,2-dichloro-ethane at 120℃; for 12h; Schlenk technique;
8
(1) Take 0.1 mmol of quinoline-3-carboxylic acid and 0.25 mmol of tetraethylthiuram disulfide, add 1 mL of 1,2-dichloroethane to make a mixture, and place the mixture in 10 mL of The Schlenk tube was heated in an oil bath at 120°C, and after 12 hours of reaction, cooled to room temperature to obtain a reaction liquid;(2) Concentrate the reaction solution obtained in step (1) directly to obtain a concentrate. Use ethyl acetate/petroleum ether = 1/1 (v/v) as the developing solvent for thin layer chromatography to obtain 18.8 mg. Target product.The target product yield of this example was 83%.
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