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Product Details of [ 26892-90-0 ]

CAS No. :26892-90-0 MDL No. :MFCD00173406
Formula : C12H11NO3 Boiling Point : -
Linear Structure Formula :- InChI Key :YBEOYBKKSWUSBR-UHFFFAOYSA-N
M.W : 217.22 Pubchem ID :220876
Synonyms :

Calculated chemistry of [ 26892-90-0 ]

Physicochemical Properties

Num. heavy atoms : 16
Num. arom. heavy atoms : 10
Fraction Csp3 : 0.17
Num. rotatable bonds : 3
Num. H-bond acceptors : 4.0
Num. H-bond donors : 1.0
Molar Refractivity : 59.85
TPSA : 59.42 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.1 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.51
Log Po/w (XLOGP3) : 3.56
Log Po/w (WLOGP) : 2.12
Log Po/w (MLOGP) : 1.33
Log Po/w (SILICOS-IT) : 2.16
Consensus Log Po/w : 2.34

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.69
Solubility : 0.0439 mg/ml ; 0.000202 mol/l
Class : Soluble
Log S (Ali) : -4.49
Solubility : 0.00698 mg/ml ; 0.0000321 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -3.61
Solubility : 0.0528 mg/ml ; 0.000243 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 1.72

Safety of [ 26892-90-0 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P305+P351+P338 UN#:N/A
Hazard Statements:H319 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 26892-90-0 ]

* 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.

  • Upstream synthesis route of [ 26892-90-0 ]
  • Downstream synthetic route of [ 26892-90-0 ]

[ 26892-90-0 ] Synthesis Path-Upstream   1~22

  • 1
  • [ 26892-90-0 ]
  • [ 34785-11-0 ]
YieldReaction ConditionsOperation in experiment
92% With water; sodium hydroxide In ethanol for 3 h; Reflux 4-hydroxyquinoline-3-carboxylic acid ethyl ester (1.2 g, 0.0055 mol) was dissolved in 20 mL of ethanol,Aqueous sodium hydroxide solution (6.6 mL, 0.0165 mol) having a mass concentration of 0.1 g / mL was added thereto,Under reflux conditions for 3 h;The reaction solution was cooled to 20 ° C,4 mol / L hydrochloric acid was added to adjust the pH to 4,Precipitation of solid,After recovering 10 mL of solvent ethanol under reduced pressure,The solid was filtered and washed with a volume of ethanol and water (2 mL x 2 times)50 drying,To give 0.96 g of 4-hydroxyquinoline-3-carboxylic acid,The yield was 92percentAs an off-white solid.
Reference: [1] Molecular Crystals and Liquid Crystals Science and Technology Section A: Molecular Crystals and Liquid Crystals, 2000, vol. 344, p. 163 - 168
[2] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1995, vol. 31, # 2, p. 167 - 175[3] Khimiya Geterotsiklicheskikh Soedinenii, 1995, # 2, p. 195 - 203
[4] Patent: CN106187887, 2016, A, . Location in patent: Paragraph 0015; 0048; 0049; 0050; 0051; 0052; 0053
[5] Journal of the American Chemical Society, 1946, vol. 68, p. 1264
[6] Journal of the Chemical Society, 1948, p. 893
[7] Journal of the Chemical Society, 1946, p. 1033,1035
[8] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 5, p. 1948 - 1956
[9] European Journal of Medicinal Chemistry, 2010, vol. 45, # 5, p. 1821 - 1827
  • 2
  • [ 26892-90-0 ]
  • [ 34785-11-0 ]
  • [ 13721-01-2 ]
Reference: [1] Patent: US2011/98311, 2011, A1,
  • 3
  • [ 54535-22-7 ]
  • [ 26892-90-0 ]
YieldReaction ConditionsOperation in experiment
70%
Stage #1: at 70℃; for 4 h;
Stage #2: With sodium carbonate In water
4-Hydroxyquinoline-3-carboxylic acid ethyl ester
A 1 L three-necked flask fitted with a mechanical stirrer was charged with 2-phenylaminomethylene-malonic acid diethyl ester (26.3 g, 0.100 mol), polyphosphoric acid (270 g) and phosphoryl chloride (750 g).
The mixture was heated to 70° C. and stirred for 4 h.
The mixture was cooled to room temperature and filtered.
The residue was treated with aqueous Na2CO3 solution, filtered, washed with water and dried.
4-Hydroxyquinoline-3-carboxylic acid ethyl ester was obtained as a pale brown solid (15.2 g, 70percent).
70%
Stage #1: at 70℃; for 4 h;
Stage #2: With sodium carbonate In water at 20℃;
[0217] A l L three-necked flask fitted with a mechanical stirrer was charged with 2- phenylaminomethylene-malonic acid diethyl ester (26.3 g, 0.100 mol), polyphosphoric acid (270 g) and phosphoryl chloride (750 g). The mixture was heated to 70 0C and stirred for 4 h. The mixture was cooled to room temperature and filtered. The residue was treated with aqueous Na2CO3 solution, filtered, washed with water and dried. 4-Hydroxyquinoline-3- carboxylic acid ethyl ester was obtained as a pale brown solid (15.2 g, 70percent). The crude product was used in next step without further purification.
65% at 75℃; for 8 h; General procedure: Polyphosphoric acid (PPA) (2 equiv by weight) was added to corresponding intermediate 1 (40 mmol) to this phosphorousoxychloride (POCl3) (10 mmol) was added. The reaction mixture was heated to 75 °C for 8 h, monitored by TLC, after completion of the reaction. The reaction mixture was quenched slowly with 10percent sodium hydroxide solution by keeping it in an ice bath and the PH was adjusted to a pH ~ 7, the solid separated was filtered, dried and washed with diethyl ether (3*20 mL) to afford desired compound in good yield. 4.1.5.1. Ethyl 4-hydroxyquinoline-3-carboxylate (10a). Pale yellowsolid (5.64 g, 65percent); m.p: 276-278 C; ESI-MS was found at m/z 218.32 [M+H]+. 1H NMR (300 MHz, DMSO-d6, TMS):d 10.72 (brs,1H), 8.91 (s, 1H), 8.46e7.78 (m, 4H), 4.29 (q, J 7.1 Hz, 2H), 1.29 (t,J 7.1 Hz, 3H).
Reference: [1] Patent: US4079058, 1978, A,
[2] Patent: US2008/90864, 2008, A1, . Location in patent: Page/Page column 7
[3] Patent: WO2007/79139, 2007, A2, . Location in patent: Page/Page column 46
[4] European Journal of Medicinal Chemistry, 2015, vol. 103, p. 1 - 16
[5] Molecular Crystals and Liquid Crystals Science and Technology Section A: Molecular Crystals and Liquid Crystals, 2000, vol. 344, p. 163 - 168
[6] Journal of the American Chemical Society, 1939, vol. 61, p. 2890,2893
[7] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 12, p. 2980 - 2985
[8] Journal of Medicinal Chemistry, 2006, vol. 49, # 21, p. 6351 - 6363
[9] Patent: US2008/306048, 2008, A1, . Location in patent: Page/Page column 17
[10] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 5, p. 1948 - 1956
[11] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 2, p. 689 - 693
[12] Patent: US2012/309758, 2012, A1, . Location in patent: Page/Page column 60
[13] Patent: US2015/231142, 2015, A1, . Location in patent: Paragraph 0351
[14] Patent: WO2018/64632, 2018, A1, . Location in patent: Paragraph 00213; 00214
[15] Patent: WO2018/107100, 2018, A1, . Location in patent: Paragraph 00232; 00233
[16] Patent: US2018/280349, 2018, A1, . Location in patent: Paragraph 0096
  • 4
  • [ 62-53-3 ]
  • [ 87-13-8 ]
  • [ 26892-90-0 ]
YieldReaction ConditionsOperation in experiment
76% at 100 - 200℃; for 3 h; Aniline (1.02 mL, 0.011 mol) and diethyl ethoxymethylenemalonate (0.5-2 eq) were weighed into ethanol and heated at 100-200 ° C for three hours.Cool to room temperature, add phenyl ether, heat at 100-200 ° C for 30 min, cool to room temperature,After the reaction was completed, ice water was added, and ethyl acetate (100 mL × 2) was added, and the organic phase was combined, and the organic phase was washed with saturated brine.Dry over anhydrous sodium sulfate, filter,The organic phase was concentrated and the residue was purified by silica gel column chromatography1.6 g (76percent yield);
76% at 100 - 200℃; for 3 h; Aniline (1.02 mL, 0.011 mol) and diethyl ethoxymethylenemalonate (0.5-2 eq) were weighed into ethanol and heated at 100-200 ° C for three hours.Cool to room temperature, add phenyl ether, heat at 100-200 ° C for 30 min,Cool to room temperature,After the reaction was completed, ice water was added, and ethyl acetate was extracted (100 mL × 2).The organic phase was combined and the organic phase was washed with brine.Dry over anhydrous sodium sulfate, filter, and concentrate the organic phase.The residue was subjected to silica gel column chromatography to give the productWhite solid 1.6g (76percent yield);
69%
Stage #1: for 3 h; Reflux
Stage #2: for 1 h; Reflux
Weigh aniline (1.0 mL) and diethyl ethoxymethylenemalonate (2.2 mL) into an appropriate amount of ethanol, and heat to reflux threeAfter cooling to room temperature, add 40 mL of phenylethyl ether, reflux under heating for 1 hour, and cool to room temperature. After completion of the reaction, add ice water, extract with ethyl acetate (100 mL×2), combine the organic phase, and saturate the organic phase. The mixture was washed with brine, dried over anhydrous sodium sulfate.
66% at 90 - 100℃; for 3.5 h; Weighed aniline (0.011 mol) and diethyl ethoxymethylenemalonate (0.012 mol) were added to 20 mL of ethanol and heated at 90 ° C for three hours. Cool to room temperature, add 40 mL of phenyl ether, heat at 100 ° C for 30 min, cool to room temperature.After the reaction was completed, ice water was added, and ethyl acetate was extracted (100 mL×2).The organic phase was combined and the organic phase was washed with brine.Dry over anhydrous sodium sulfate, filter, and concentrate the organic phase.The residue was subjected to silica gel column chromatography to ethyl 4-hydroxy-2-hydro-quinoline-3-carboxylate (66percent yield)
66% at 90℃; for 3 h; Weigh aniline (0.011 mol) and diethyl ethoxymethylenemalonate (0.012 mol) into 20 mL of ethanol.Heated at 90 oC for three hours,Cool to room temperature, add 40 mL of phenyl ether and heat at 100 °C for 30 min.After cooling to room temperature, after completion of the reaction, ice water was added, and ethyl acetate was extracted (100 mL×2), the organic phase was combined, and the organic phase was saturated.Washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated.The residue was subjected to silica gel column chromatography toield ethyl 4-hydroxy-2-hydro-quinoline-3-carboxylate (66percent yield)
32%
Stage #1: at 20 - 110℃; for 17 h;
Stage #2: at 255℃; for 0.333333 h;
Synthesis of Lipophilic Group Modified Peptide Sequence Based on Nisvastatin; Scheme A; Scheme A; Ethyl 4-hydroxyquinoline-3-carboxylate (Al); [0183] Aniline (2.15g, 23mmol) and diethyl ethoxymethylene malonate (5g, 23mmol) were mixed neat and heated at 110°C for 2h then cooled and allowed to stand at room temperature for 15h. During this time the reaction mixture crystallized. [0184] Dowtherm A (70 mL) was heated to 255°C and the melted crystals were added and the mixture heated at 255°C for 20 min. The mixture was then poured into a stainless steel container cooled to 0°C with an ice bath. Hexanes were added to the cold solution to precipitate the product which was collected by filtration and rinsed with another portion of hexanes. The product was recrystallized from EtOH to give the product as a white solid. (1.6g, 7.3mmol, 32percent, M.P. 309C) that was used without further purification in the next step.

Reference: [1] Patent: CN108623581, 2018, A, . Location in patent: Page/Page column 6
[2] Patent: CN108623561, 2018, A, . Location in patent: Paragraph 0014
[3] Patent: CN108690024, 2018, A, . Location in patent: Paragraph 0144
[4] Patent: CN108623562, 2018, A, . Location in patent: Paragraph 0067
[5] Patent: CN108623560, 2018, A, . Location in patent: Page/Page column 36
[6] Patent: WO2005/123686, 2005, A1, . Location in patent: Page/Page column 75-76
[7] Journal of Medicinal Chemistry, 1993, vol. 36, # 11, p. 1669 - 1673
[8] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 8, p. 1487 - 1490
[9] European Journal of Medicinal Chemistry, 2010, vol. 45, # 5, p. 1821 - 1827
[10] Patent: US2012/309758, 2012, A1,
[11] Patent: WO2018/107100, 2018, A1,
[12] Patent: US2018/280349, 2018, A1,
  • 5
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YieldReaction ConditionsOperation in experiment
71% at 120℃; for 4 h; Ethyl 3- (2-aminophenyl) -3-oxopropionate (20.7 g, 0.1 mol) was dissolved in 100 mL of N, N-dimethylformamide,N, N-dimethylformamide dimethyl acetal (24.0 g, 0.2 mol) was added thereto, and the reaction was carried out at 120 ° C for 4 hours.The reaction solution was cooled to 20 ° C and the solvent was concentrated under reduced pressure. The residue was added to 200 g of ice water and stirred for 2 h.Ethanol and water volume (30mLx2 times), 50 drying, with 160mL ethyl acetate and petroleum ether equal volume mixedWas purified by recrystallization to obtain 15.4 g of ethyl 4-hydroxyquinoline-3-carboxylate in 71percent yield as an off-white solid.
Reference: [1] Patent: CN106187887, 2016, A, . Location in patent: Paragraph 0015; 0063; 0064; 0065; 0046; 0047
  • 6
  • [ 40516-46-9 ]
  • [ 62-53-3 ]
  • [ 26892-90-0 ]
YieldReaction ConditionsOperation in experiment
86% for 3.5 h; Reflux Weigh aniline (1.0 mL) and diethyl ethoxymethanemalonate (2.2 mL), add to the appropriate amount of ethanol, heat to reflux for three hours, cool to room temperature, add 40 mL of phenyl ether, and reflux under heating for 30 min.After cooling to room temperature, after completion of the reaction, ice water was added and extracted with ethyl acetate (100 mL×2).The combined organic phase was washed with brine, dried over anhydrous sodium sulfateThe residue was subjected to silica gel column chromatography to give the product(86percent yield).
Reference: [1] Patent: CN108623589, 2018, A, . Location in patent: Paragraph 0141; 0148
  • 7
  • [ 87-13-8 ]
  • [ 26892-90-0 ]
Reference: [1] Patent: EP1308439, 2003, A1,
[2] Patent: US2011/98311, 2011, A1,
[3] European Journal of Medicinal Chemistry, 2015, vol. 103, p. 1 - 16
[4] Patent: US2015/231142, 2015, A1,
[5] Patent: WO2018/64632, 2018, A1,
  • 8
  • [ 54535-22-7 ]
  • [ 497-19-8 ]
  • [ 26892-90-0 ]
Reference: [1] Patent: US2011/98311, 2011, A1,
  • 9
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  • [ 26892-90-0 ]
Reference: [1] Journal of the American Chemical Society, 1954, vol. 76, p. 2760
[2] Journal of the Chemical Society, 1946, p. 1035
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Reference: [1] Journal of the American Chemical Society, 1954, vol. 76, p. 2760
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Reference: [1] Journal of the American Chemical Society, 1954, vol. 76, p. 2760
  • 12
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  • [ 26892-90-0 ]
Reference: [1] European Journal of Medicinal Chemistry, 2015, vol. 103, p. 1 - 16
[2] Patent: US2015/231142, 2015, A1,
[3] Patent: WO2018/64632, 2018, A1,
  • 13
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Reference: [1] Chemistry Letters, 2001, # 7, p. 602 - 603
  • 14
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Reference: [1] Chemistry Letters, 2001, # 7, p. 602 - 603
  • 15
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  • [ 26892-90-0 ]
Reference: [1] Chemistry Letters, 2001, # 7, p. 602 - 603
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  • [ 26892-90-0 ]
Reference: [1] Patent: CN106187887, 2016, A,
  • 17
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  • [ 26892-90-0 ]
Reference: [1] Patent: CN106187887, 2016, A,
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  • [ 54535-22-7 ]
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Reference: [1] Journal of the American Chemical Society, 1946, vol. 68, p. 1264
  • 19
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YieldReaction ConditionsOperation in experiment
87%
Stage #1: at 110℃; for 0.333333 h;
Stage #2: With ammonia In water at 0℃;
Ethyl 4-chloroquinoline-3-carboxylate (A2); [0185] To solid ethyl 4-hydroxyquinoline-3-carboxylate (A1) (1.5g, 7mmol) was added POC13 (2.2g, 1.3mL, 14mmol) and the mixture heated at 110°C for 20 min. The mixture was poured into NH3 (aq, 28-30percent) and ice and then stirred until granular. The melted ice mixture was extracted with ether (3x40mL) and the combined organic layers dried (MgS04), filtered, and concentrated to give the product as an oil that crystallized on standing (1.44g, 6mmol, 87percent) that was used as is without further purification.
81% for 3 h; Reflux General procedure: To the corresponding intermediate 10 (25 mmol), POCl3 (125 mmol) was added slowly and refluxed for 3 h at 105 °C. TLC analysis indicated that the reaction was completed. Excess POCl3 was removed under reduced pressure and the crude reaction mass was quenched with crushed ice then neutralized with saturated sodium bicarbonate solution (100 mL) and extracted with ethyl acetate(3*100 mL). The organic layer was dried over anhy. Na2SO4, filtered and evaporated under reduced pressure to get corresponding desired chloro intermediate. 4.1.6.1. Ethyl 4-chloroquinoline-3-carboxylate (11a). Yellow solid (4.74 g, 81percent); m.p: 43-45 C; ESI-MS was found at m/z 236.67[M+H]+. 1H NMR (300 MHz, CDCl3, TMS): d 8.92 (s, 1H), 8.46e7.78(m, 4H), 4.28 (q, J 6.8 Hz, 2H), 1.27 (t, J 7.3 Hz, 3H).
74% With trichlorophosphate In 1,4-dioxane for 0.5 h; Reflux Weigh 4-hydroxyquinoline-3-carboxylic acid ethyl ester (2.0 g) dissolved in an appropriate amount of dioxane, then add phosphorus oxychlorideAfter mixing (0.68 mL), the mixture was heated under reflux for 30 min. After the reaction was completed, the reaction solution was poured into ice water, the pH was adjusted to neutral with saturated potassium carbonate solution, ethyl acetate was extracted (100 mL×2), and the organic phase was combined. The organic phase was washed with brine, dried over anhydrous sodium sulfateThe residue was subjected to silica gel column chromatography to give the product(74percent yield).
64% With trichlorophosphate In tetrahydrofuran at 100℃; for 1 h; Ethyl 4-hydroxyquinoline-3-carboxylate (1.6 g, 7.3 mmol) was weighed and dissolved in tetrahydrofuran, and then mixed with phosphorus oxychloride (0.5-10 eq), and heated at 100 ° C for one hour.After the reaction is over, the reaction solution is poured into ice water.The pH was adjusted to neutrality with a saturated aqueous solution of sodium hydrogencarbonate, and ethyl acetate was extracted (100 mL×2). The organic phase was combined and the organic phase was washed with brine.Dry over anhydrous sodium sulfate, filter, and concentrate the organic phase.The residue was chromatographed on silica gel to give a white solid.1.1 g (64percent yield);
64% With trichlorophosphate In tetrahydrofuran at 100℃; for 1 h; Ethyl 4-hydroxyquinoline-3-carboxylate (1.6 g, 7.3 mmol) was weighed and dissolved in tetrahydrofuran, followed by the addition of phosphorus oxychloride.(0.5-10 eq) After mixing, heat at 100 ° C for one hour. After the reaction is over, pour the reaction solution into ice water with saturated hydrogen carbonate.Potassium solution was adjusted to pH, and ethyl acetate was extracted (100 mL×2). The organic phase was combined and the organic phase was washed with brine.Dry over anhydrous sodium sulfate, filter, and concentrate the organic phase.The residue was subjected to silica gel column chromatography to give the productWhite solid 1.1 g (64percent yield);
63% With trichlorophosphate In 1,4-dioxane for 1 h; Reflux WeighEthyl 4-hydroxy-2-hydro-quinoline-3-carboxylate(2.0 g) was dissolved in an appropriate amount of dioxane, then added with phosphorus oxychloride (0.68 mL), and then heated under reflux for 1 hour. After the reaction was completed, the reaction solution was poured into ice water and extracted with ethyl acetate (100 mL) The organic phase is combined, the organic phase is washed with brine, dried over anhydrous sodium sulfate(63percent yield).
58% With trichlorophosphate In 1,4-dioxane at 80℃; for 1 h; Ethyl 4-hydroxyquinoline-3-carboxylate (7.3 mmol) was dissolved in 100 mL of dioxane, then added with phosphorus oxychloride (7.4 mmol) and heated at 80 ° C for one hour.After the reaction is over, the reaction solution is poured into ice water.Adjust the pH to neutral with saturated sodium carbonate solution,Ethyl acetate extraction (100 mL×2),The organic phase was combined and the organic phase was washed with brine.Dry over anhydrous sodium sulfate,Filtered, concentrated organic phase,The residue was subjected to silica gel column chromatography to ethyl 4-chloroquinoline-3-carboxylate (yield: 58percent);
58% With trichlorophosphate In 1,4-dioxane at 80℃; for 1 h; Ethyl 4-hydroxy-2-hydro-quinoline-3-carboxylate (7.3 mmol) was dissolved in 100 mL of dioxane. Then add phosphorus oxychloride (7.4 mmol) and heat at 80 °C for one hour.After the reaction was completed, the reaction mixture was poured into ice water, and the mixture was adjusted to neutral with a saturated sodium carbonate solution, ethyl acetate (100 mL×2), and the organic phase was combined. , filtering,The organic phase is concentrated, and the residue is obtained by silica gel column chromatography.4-chloroquinoline-3-carboxylic acid ethyl ester (58percent yield)

Reference: [1] Journal of Medicinal Chemistry, 2006, vol. 49, # 21, p. 6351 - 6363
[2] Patent: WO2005/123686, 2005, A1, . Location in patent: Page/Page column 75-76
[3] European Journal of Medicinal Chemistry, 2015, vol. 103, p. 1 - 16
[4] Patent: CN108623589, 2018, A, . Location in patent: Paragraph 0142; 0149
[5] Patent: CN108623581, 2018, A, . Location in patent: Page/Page column 7
[6] Patent: CN108623561, 2018, A, . Location in patent: Paragraph 0015
[7] Patent: CN108690024, 2018, A, . Location in patent: Paragraph 0144; 0145
[8] Patent: CN108623562, 2018, A, . Location in patent: Paragraph 0067
[9] Patent: CN108623560, 2018, A, . Location in patent: Page/Page column 36-37
[10] Yakugaku Zasshi, 1952, vol. 72, p. 1109[11] Chem.Abstr., 1953, p. 6946
[12] Journal of Organic Chemistry, 1953, vol. 18, p. 55,56
[13] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 8, p. 1487 - 1490
[14] Journal of the Chemical Society, 1951, p. 1389,1391
[15] Journal of Medicinal Chemistry, 1993, vol. 36, # 11, p. 1669 - 1673
[16] Patent: US2008/306048, 2008, A1, . Location in patent: Page/Page column 17
[17] Patent: WO2009/21961, 2009, A1, . Location in patent: Page/Page column 19
[18] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 2, p. 689 - 693
  • 20
  • [ 26892-90-0 ]
  • [ 13721-01-2 ]
YieldReaction ConditionsOperation in experiment
92%
Stage #1: for 2 h; Heating / reflux
Stage #2: With hydrogenchloride In water
4-Oxo-1,4-dihydroquinoline-3-carboxylic acid
4-Hydroxyquinoline-3-carboxylic acid ethyl ester (15 g, 69 mmol) was suspended in sodium hydroxide solution (2N, 150 mL) and stirred for 2 h at reflux.
After cooling, the mixture was filtered, and the filtrate was acidified to pH 4 with 2N HCl.
The resulting precipitate was collected via filtration, washed with water and dried under vacuum to give 4-oxo-1,4-dihydroquinoline-3-carboxylic acid as a pale white solid (10.5 g, 92percent).
1H NMR (DMSO-d6) δ 15.34 (s, 1H), 13.42 (s, 1H), 8.89 (s, 1H), 8.28 (d, J=8.0 Hz, 1H), 7.88 (m, 1H), 7.81 (d, J=8.4 Hz, 1H), 7.60 (m, 1H).
92%
Stage #1: for 2 h; Heating / reflux
Stage #2: With hydrogenchloride In water
[0219] 4-Hydroxyquinoline-3-carboxylic acid ethyl ester (15 g, 69 mmol) was suspended in sodium hydroxide solution (2N, 150 mL) and stirred for 2 h at reflux. After cooling, the mixture was filtered, and the filtrate was acidified to pH 4 with 2N HCl. The <n="49"/>resulting precipitate was collected via filtration, washed with water and dried under vacuum to give 4-oxo-l,4-dihydroquinoline-3-carboxylic acid as a pale white solid (10.5 g, 92 percent). 1H NMR (DMSO-flfe) δ 15.34 (s, 1 H), 13.42 (s, 1 H), 8.89 (s, IH), 8.28 (d, J= 8.0 Hz, IH), 7.88 (m, IH), 7.81 (d, J = 8.4 Hz, IH), 7.60 (m, IH).
10.5 g for 2 h; Reflux 4-Hydroxyquinoline-3-carboxylic acid ethyl ester (15 g, 69 mmol) was suspended in sodium hydroxide solution (2N, 150 mL) and stirred for 2 h at reflux. After cooling, the mixture was filtered, and the filtrate was acidified to pH 4 with 2N HCl. The resulting precipitate was collected via filtration, washed with water and dried under vacuum to give 4-oxo-l,4-dihydroquinoline-3-carboxylic acid as a pale white solid (10.5 g, 92 percent). 1H NMR (DMSO-
10.5 g for 2 h; Reflux 4-Hydroxyquinoline-3-carboxylic acid ethyl ester (15 g, 69 mmol) was suspended in sodium hydroxide solution (2N, 150 mL) and stirred for 2 h at reflux. After cooling, the mixture was filtered, and the filtrate was acidified to pH 4 with 2N HCl. The resulting precipitate was collected via filtration, washed with water and dried under vacuum to give 4-oxo-1,4-dihydroquinoline-3-carboxylic acid as a pale white solid (10.5 g, 92 percent).1H NMR (DMSO-d6) δ 15.34 (s, 1 H), 13.42 (s, 1 H), 8.89 (s, 1H), 8.28 (d, J = 8.0 Hz, 1H), 7.88 (m, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.60 (m, 1H).
10.5 g for 2 h; Reflux Step C:
4-Oxo-1,4-dihydroquinoline-3-carboxylic acid
4-Hydroxyquinoline-3-carboxylic acid ethyl ester (15 g, 69 mmol) was suspended in a sodium hydroxide solution (2N, 150 mL) and stirred for 2 h at reflux.
After cooling, the mixture was filtered, and the filtrate was acidified to pH 4 with 2N HCl.
The resulting precipitate was collected via filtration, washed with water and dried under vacuum to give 4-oxo-1,4-dihydroquinoline-3-carboxylic acid as a pale white solid (10.5 g, 92percent).
1H NMR (DMSO-d6) δ 15.34 (s, 1H), 13.42 (s, 1H), 8.89 (s, 1H), 8.28 (d, J=8.0 Hz, 1H), 7.88 (m, 1H), 7.81 (d, J=8.4 Hz, 1H), 7.60 (m, 1H) ppm.
10.5 g for 2 h; Reflux 4-Hydroxyquinoline-3-carboxylic acid ethyl ester (15 g, 69 mmol) was suspended in sodium hydroxide solution (2N, 150 mL) and stirred for 2 h at reflux. After cooling, the mixture was filtered, and the filtrate was acidified to pH 4 with 2N HC1. The resulting precipitate was collected via filtration, washed with water and dried under vacuum to give 4-oxo-l,4-dihydroquinoline-3-carboxylic acid as a pale white solid (10.5 g, 92 percent). lU NMR (DMSO-4) δ 15.34 (s, 1 H), 13.42 (s, 1 H), 8.89 (s, 1H), 8.28 (d, J = 8.0 Hz, 1H), 7.88 (m, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.60 (m, 1H).

Reference: [1] Patent: US2008/90864, 2008, A1, . Location in patent: Page/Page column 7
[2] Patent: WO2007/79139, 2007, A2, . Location in patent: Page/Page column 46; 47
[3] Patent: US2012/309758, 2012, A1, . Location in patent: Page/Page column 61
[4] Patent: US2015/231142, 2015, A1, . Location in patent: Paragraph 0352
[5] Patent: WO2018/64632, 2018, A1, . Location in patent: Paragraph 00215; 00216
[6] Patent: WO2018/107100, 2018, A1, . Location in patent: Paragraph 00234; 00235
[7] Patent: US2018/280349, 2018, A1, . Location in patent: Paragraph 0097
[8] Patent: WO2018/227049, 2018, A1, . Location in patent: Paragraph 00206; 00207
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Reference: [1] Patent: US2011/98311, 2011, A1,
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Reference: [1] Patent: CN108623589, 2018, A,
[2] Patent: CN108623562, 2018, A,
[3] Patent: CN108690024, 2018, A,
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