[ CAS No. 492-27-3 ] {[proInfo.proName]}

Name: 492-27-3|4-Hydroxyquinoline-2-carboxylic Acid|97%
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SKU: A141971
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2D 3D

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Quality Control of [ 492-27-3 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 492-27-3 ]

SDS Specification

Alternatived Products of [ 492-27-3 ]

Product Details of [ 492-27-3 ]

CAS No. :	492-27-3	MDL No. :	MFCD00149476
Formula :	C₁₀H₇NO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	HCZHHEIFKROPDY-UHFFFAOYSA-N
M.W :	189.17	Pubchem ID :	3845
Synonyms :	Quinurenic acid;Kynurenic acid;Kynuronic acid;Kynurenate

Calculated chemistry of [ 492-27-3 ]

Physicochemical Properties

Num. heavy atoms :	14
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	4.0
Num. H-bond donors :	2.0
Molar Refractivity :	50.73
TPSA :	70.42 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.25 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.07
Log Po/w (XLOGP3) :	1.69
Log Po/w (WLOGP) :	1.64
Log Po/w (MLOGP) :	-0.35
Log Po/w (SILICOS-IT) :	1.31
Consensus Log Po/w :	1.07

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-2.54
Solubility :	0.545 mg/ml ; 0.00288 mol/l
Class :	Soluble
Log S (Ali) :	-2.78
Solubility :	0.311 mg/ml ; 0.00165 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.5
Solubility :	0.597 mg/ml ; 0.00316 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.49

Safety of [ 492-27-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 492-27-3 ]

* 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 [ 492-27-3 ]
Downstream synthetic route of [ 492-27-3 ]

[ 492-27-3 ] Synthesis Path-Upstream 1~12

1
[ 343-65-7 ]
[ 492-27-3 ]

Reference： [1] Patent: US5002963, 1991, A,
[2] Journal of Medicinal Chemistry, 2009, vol. 52, # 9, p. 2786 - 2793

2
[ 2922-83-0 ]
[ 492-27-3 ]

Reference： [1] Journal of Antibiotics, 2011, vol. 64, # 1, p. 117 - 122

3
[ 529-92-0 ]
[ 492-27-3 ]

Reference： [1] Chemische Berichte, 1924, vol. 57, p. 1246
[2] Archiv der Pharmazie (Weinheim, Germany), 1913, vol. 251, p. 281
[3] Archiv der Pharmazie (Weinheim, Germany), 1920, vol. 258, p. 254

4
[ 52144-34-0 ]
[ 492-27-3 ]

Reference： [1] Yakugaku Zasshi, 1950, vol. 70, p. 423

5
[ 401640-33-3 ]
[ 492-27-3 ]

Reference： [1] Chemische Berichte, 1901, vol. 34, p. 2709[2] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1901, vol. 33, p. 402

6
[ 446251-68-9 ]
[ 492-27-3 ]

Reference： [1] Gazzetta Chimica Italiana, 1950, vol. 80, p. 161,169

7
[ 577-59-3 ]
[ 492-27-3 ]

Reference： [1] Gazzetta Chimica Italiana, 1950, vol. 80, p. 161,169

8
[ 94298-60-9 ]
[ 492-27-3 ]

Reference： [1] Yakugaku Zasshi, 1950, vol. 70, p. 423

9
[ 857762-80-2 ]
[ 492-27-3 ]

Reference： [1] Yakugaku Zasshi, 1950, vol. 70, p. 423

10
[ 178114-28-8 ]
[ 492-27-3 ]

Reference： [1] Gazzetta Chimica Italiana, 1950, vol. 80, p. 161,169

11
[ 492-27-3 ]
[ 209003-46-3 ]

Reference： [1] Tetrahedron Letters, 2001, vol. 42, # 29, p. 4849 - 4851

12
[ 67-56-1 ]
[ 492-27-3 ]
[ 5965-59-3 ]

Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: for 24 h; Reflux Stage #2: With sodium hydrogencarbonate In methanol; water	EXAMPLE III Synthesis of 4-quinoline triazole derivatives; Ccncral Scheme:; Methyl 4-hydroxyquinoline-2-carboxylate, 5': 500 mg of kynurenic acid (2.65 mmol) were suspended in anhydrous methanol and 40 drops of concentrated H₂S0₄ (96percent) were added, the solution became clear. Then the reaction was heated to reflux and allowed to react under reflux for 24 hrs (until no starting material was observed in LC-MS). Then it was cooled to room temperature. The solvent was evaporated to dryness using rotatory evaporator. The produced solid was dissolved in 1 ml of methanol, and 10 ml of DDW were added. Addition of saturated sodium bicarbonate produced a white precipitate. The precipitate was filtrated and washed with diethylether. White solid, 65 percent (0.35 g). 1H NMR (DMSO, I OVA-500): (53.52 (s, 3H), 6.48 (s, 1H), 7.25 (t, 1H, J= 7.0 Hz), 7.58 (t, 1H, J= 7.0 Hz), 7.96 (d, 1H, J= 8.5 Hz), 8.05 (d, 1H, J= 8.5 Hz), 11.32 (s, 1H); LC-MS (ES+): mlz 204.09, calcd 204.06 (M+).

Reference： [1] Journal of Medicinal Chemistry, 2002, vol. 45, # 3, p. 559 - 562
[2] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 20, p. 5453 - 5463
[3] Patent: WO2012/6068, 2012, A2, . Location in patent: Page/Page column 67-68
[4] Monatshefte fuer Chemie, 1921, vol. 42, p. 100[5] Monatshefte fuer Chemie, 1922, vol. 43, p. 479
[6] Journal of Medicinal Chemistry, 2012, vol. 55, # 22, p. 9589 - 9606

[ 492-27-3 ] Synthesis Path-Downstream 1~87

1
[ 67-56-1 ]
[ 492-27-3 ]
[ 5965-59-3 ]

Yield	Reaction Conditions	Operation in experiment
65%		EXAMPLE III Synthesis of 4-quinoline triazole derivatives; Ccncral Scheme:; Methyl 4-hydroxyquinoline-2-carboxylate, 5': 500 mg of <strong>[492-27-3]kynurenic acid</strong> (2.65 mmol) were suspended in anhydrous methanol and 40 drops of concentrated H2S04 (96%) were added, the solution became clear. Then the reaction was heated to reflux and allowed to react under reflux for 24 hrs (until no starting material was observed in LC-MS). Then it was cooled to room temperature. The solvent was evaporated to dryness using rotatory evaporator. The produced solid was dissolved in 1 ml of methanol, and 10 ml of DDW were added. Addition of saturated sodium bicarbonate produced a white precipitate. The precipitate was filtrated and washed with diethylether. White solid, 65 % (0.35 g). 1H NMR (DMSO, I OVA-500): (53.52 (s, 3H), 6.48 (s, 1H), 7.25 (t, 1H, J= 7.0 Hz), 7.58 (t, 1H, J= 7.0 Hz), 7.96 (d, 1H, J= 8.5 Hz), 8.05 (d, 1H, J= 8.5 Hz), 11.32 (s, 1H); LC-MS (ES+): mlz 204.09, calcd 204.06 (M+).

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 559 - 562
[2]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 5453 - 5463
[3]Patent: WO2012/6068,2012,A2 .Location in patent: Page/Page column 67-68
[4]Monatshefte fur Chemie,1921,vol. 42,p. 100
Monatshefte fuer Chemie,1922,vol. 43,p. 479
[5]Journal of Medicinal Chemistry,2012,vol. 55,p. 9589 - 9606

2
[ 492-27-3 ]
1-hydroxy-4-oxo-1,4-dihydro-quinoline-2-carboxylic acid [ No CAS ]

Reference： [1]Gazzetta Chimica Italiana,1950,vol. 80,p. 161,169

3
[ 492-27-3 ]
[ 529-37-3 ]

Reference： [1]Journal of the American Chemical Society,1944,vol. 66,p. 1166,1168
[2]Journal of the American Chemical Society,1946,vol. 68,p. 2685
[3]Monatshefte fur Chemie,1881,vol. 2,p. 68

4
[ 52144-34-0 ]
[ 492-27-3 ]

Reference： [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1950,vol. 70,p. 423

5
[ 529-92-0 ]
[ 492-27-3 ]

Reference： [1]Chemische Berichte,1924,vol. 57,p. 1246

6
[ 401640-33-3 ]
[ 492-27-3 ]

Reference： [1]Chemische Berichte,1901,vol. 34,p. 2709
Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie,1901,vol. 33,p. 402

7
[ 492-27-3 ]
[ 541-41-3 ]
[ 78797-48-5 ]

Reference： [1]Heterocycles,1981,vol. 16,p. 751 - 754

8
[ 492-27-3 ]
[ 136631-67-9 ]
[ 127368-98-3 ]

Reference： [1]Journal of Medicinal Chemistry,1991,vol. 34,p. 3350 - 3359

9
[ 492-27-3 ]
[ 168141-98-8 ]

Reference： [1]Gazzetta Chimica Italiana,1995,vol. 125,p. 69 - 76

10
[ 492-27-3 ]
[ 33925-79-0 ]

Reference： [1]Journal of Chemical Research, Miniprint,1995,p. 1051 - 1063

11
[ 492-27-3 ]
[ 52144-34-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 5453 - 5463
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 559 - 562

12
[ 492-27-3 ]
[ 102028-50-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 5453 - 5463
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 559 - 562

13
[ 492-27-3 ]
4-hydroxyquinoline-2-carboxylic acid [2-(3,4-dihydroxy-5-oxo-2,5-dihydrofuran-2(R)-yl)-2(S)-hydroxyethyl] ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 5453 - 5463
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 559 - 562

14
[ 492-27-3 ]
[ 400844-99-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 5453 - 5463
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 559 - 562

15
[ 492-27-3 ]
4-hydroxyquinoline-2-carboxylic acid [(2R)-2-(3,4-dihydroxy-5-oxo-2,5-dihydrofuran-2-yl)-(1S)-2-bromo-ethyl] ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 5453 - 5463

16
[ 492-27-3 ]
[ 798576-75-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 5453 - 5463

17
[ 492-27-3 ]
C₅₄H₄₂N₂O₁₀ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 5453 - 5463

18
[ 492-27-3 ]
(R)-2-[(4-Hydroxy-quinoline-2-carbonyl)-amino]-3-methyl-butyric acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 4719 - 4727

19
[ 492-27-3 ]
4-Hydroxy-quinoline-2-carboxylic acid [(R)-1-((1S,2R,4S)-4-amino-1-benzyl-2-hydroxy-5-phenyl-pentylcarbamoyl)-2-methyl-propyl]-amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 4719 - 4727

20
[ 492-27-3 ]
4-Hydroxy-quinoline-2-carboxylic acid [(R)-1-((1S,2S,4S)-4-amino-1-benzyl-2-hydroxy-5-phenyl-pentylcarbamoyl)-2-methyl-propyl]-amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 4719 - 4727

21
[ 492-27-3 ]
((1S,2R,4S)-4-Amino-1-benzyl-2-hydroxy-5-phenyl-pentyl)-{(R)-2-[(4-hydroxy-quinoline-2-carbonyl)-amino]-3-methyl-butyryl}-carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 4719 - 4727

22
[ 492-27-3 ]
((1S,2S,4S)-4-Amino-1-benzyl-2-hydroxy-5-phenyl-pentyl)-{(R)-2-[(4-hydroxy-quinoline-2-carbonyl)-amino]-3-methyl-butyryl}-carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 4719 - 4727

23
[ 492-27-3 ]
4-Hydroxy-quinoline-2-carboxylic acid ((R)-1-{(1S,2R,4S)-1-benzyl-4-[2-(2,6-dimethyl-phenoxy)-acetylamino]-2-hydroxy-5-phenyl-pentylcarbamoyl}-2-methyl-propyl)-amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 4719 - 4727

24
[ 492-27-3 ]
4-Hydroxy-quinoline-2-carboxylic acid ((R)-1-{(1S,2S,4S)-1-benzyl-4-[2-(2,6-dimethyl-phenoxy)-acetylamino]-2-hydroxy-5-phenyl-pentylcarbamoyl}-2-methyl-propyl)-amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 4719 - 4727

25
[ 492-27-3 ]
C₄₈H₅₂N₆O₇ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 4719 - 4727

26
[ 492-27-3 ]
2-(5-phenyl-oxazol-2-yl)-quinolin-4-ol [ No CAS ]

Reference： [1]Tetrahedron Letters,2002,vol. 43,p. 5083 - 5086

27
[ 492-27-3 ]
[2-(5-cyclohexylamino-[1,3,4]thiadiazol-2-yl)-quinolin-4-yl]-<i>p</i>-tolyl-amine [ No CAS ]

Reference： [1]Egyptian Journal of Chemistry,1999,vol. 42,p. 413 - 419

28
[ 492-27-3 ]
[2-(5-cyclohexylamino-[1,3,4]thiadiazol-2-yl)-quinolin-4-yl]-(4-fluoro-phenyl)-amine [ No CAS ]

Reference： [1]Egyptian Journal of Chemistry,1999,vol. 42,p. 413 - 419

29
[ 492-27-3 ]
(4-chloro-phenyl)-[2-(5-cyclohexylamino-[1,3,4]thiadiazol-2-yl)-quinolin-4-yl]-amine [ No CAS ]

Reference： [1]Egyptian Journal of Chemistry,1999,vol. 42,p. 413 - 419

30
[ 492-27-3 ]
[ 168141-99-9 ]

Reference： [1]Gazzetta Chimica Italiana,1995,vol. 125,p. 69 - 76

31
[ 492-27-3 ]
(Z)-3-(4'-hydroxyquinol-2'-yl)methylen-2-oxindole [ No CAS ]

Reference： [1]Gazzetta Chimica Italiana,1995,vol. 125,p. 69 - 76

32
[ 577-59-3 ]
[ 492-27-3 ]

Reference： [1]Gazzetta Chimica Italiana,1950,vol. 80,p. 161,169

33
[ 492-27-3 ]
1-hydroxy-4-oxo-1,4-dihydro-quinoline-2-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Gazzetta Chimica Italiana,1950,vol. 80,p. 161,169

34
[ 94298-60-9 ]
[ 492-27-3 ]

Reference： [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1950,vol. 70,p. 423

35
[ 857762-80-2 ]
[ 492-27-3 ]

Reference： [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1950,vol. 70,p. 423

36
[ 178114-28-8 ]
[ 492-27-3 ]

Reference： [1]Gazzetta Chimica Italiana,1950,vol. 80,p. 161,169

37
[ 492-27-3 ]
[ 67976-94-7 ]

Reference： [1]Monatshefte fur Chemie,1921,vol. 42,p. 100
Monatshefte fuer Chemie,1922,vol. 43,p. 479

38
[ 548773-04-2 ]
[ 492-27-3 ]
2-[[4-[4-[(4-bromophenyl)(ethoxyimino)methyl]-1-piperidinyl]-4-methyl-1-piperidinyl]carbonyl]-4-quinolinol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; HATU; In DMF (N,N-dimethyl-formamide); at 20℃; for 24h;	To a solution of 4- [ (4-bromophenyl) (ethoxyimino) methyl]-1- (4-methyl-4- piperidinyl) piperidine (100MG, 0. 24mmol), 4-hydroxy-2-quinolinecarboxylic acid (56mg, 0. 29MMOL) and Et3N (87mg, 0. 86MMOL) in DMF (6 mL), HATU (119mg, 0.31 mmol) was added at room temperature and the reaction was stirred for 24 h. The reaction mixture was poured into ice water and the first crop of solid was collected by filtration. The water layer was extracted with ethyl acetate and the organic layer was washed with NaHCO3, dried and concentrated to give the second crop of solid. The two crops of crude were combined and purified by flash chromatography (2% to 10%, MeOH/CH2Cl2) to afford the title compound as an off white solid. MS 578 (M+).

Reference： [1]Patent: WO2004/113323,2004,A1 .Location in patent: Page 35

39
[ 492-27-3 ]
[ 100-39-0 ]
benzyl 4-hydroxyquinoline-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With NaH; In N-methyl-pyrrolidinone (NMP);	Benzyl 4-hydroxyquinoline-2-carboxylate To <strong>[492-27-3]4-hydroxyquinoline-2-carboxylic acid</strong> (2.08 g. 11 mmol) in N-methyl-pyrrolidinone (NMP) (20 mL) was added 60% NaH (290 mg, 12.1 mmol). The cloudy reaction mixture was heated to 40 C. for 1 hour to afford a clear yellow solution. To the mixture was added benzyl bromide (1.31 mL, 11 mmol) and the reaction mixture was stirred overnight at 40 C. After cooling the reaction mixture was poured into water (100 mL). The resulting precipitate was collected by filtration, washed with 20% ethyl acetate/hexanes (100 mL) and dried to afford the product (2.44 g, 79%). 1H NMR (300 MHz, DMSO) delta8.08 (d, 1H, J=8.0 Hz), 7.95 (d, 1H, J=8.4 Hz), 7.72 (apparent t, 1H, J=7.0 Hz), 7.52 (d, 1H, J=7.3 Hz), 7.41 (m, 5H), 6.64 (d, 1H, J=9.0 Hz), 5.46 (s, 2H).

Reference： [1]Patent: US2002/77491,2002,A1

40
[ 186581-53-3 ]
[ 492-27-3 ]
[ 90411-17-9 ]

Yield	Reaction Conditions	Operation in experiment
73%	In tetrahydrofuran;	a) <strong>[492-27-3]Kynurenic acid</strong> methyl ester An ether solution of diazomethane (100 ml, 1.5 g) was dropped during 15 min. to a suspension of <strong>[492-27-3]kynurenic acid</strong> (3.0 g, 0.016 mmole) in distilled tetrahydrofuran (200 ml) at 0 C. and under magnetic stirring. Then the reaction mixture is left to warm to room temperature and stirring is continued until complete dissolution of the starting product. Solvent is evaporated off to obtain a crude product which is subjected to flash chromatography on SiO2 (d. 4 cm; h 16 cm) eluding with chloroform (800 ml) and 95:5 chloroform-methanol (800 ml). 2.2 g of the title compound are obtained (73% yield), m.p. 224-226 C. 1 H--NMR (CDCl3 +CD3) delta: 3.95 (s, 3H); 7.45 (m, 4H); 8.15 (d, 1H) ppm.

Reference： [1]Patent: US5250541,1993,A

41
[ 492-27-3 ]
[ 105-36-2 ]
[ 133223-26-4 ]

Yield	Reaction Conditions	Operation in experiment
	With NaH; In N,N-dimethyl-formamide;	EXAMPLE 16 4-carboxymethyloxy-2-quinolinecarboxylic acid The purpose of this example is to demonstrate another method by which 4-carboxymethyloxy-2-quinolinecarboxylic acid may be produced from <strong>[492-27-3]kynurenic acid</strong>, (4-hydroxy-2-quinolinecarboxlic acid), which is commercially available. NaH (50% in oil, 2.24 g, 0.046 m) was washed 2x with 25 ml portions of sieve-dried hexane, then covered with 35 ml sieve-dried DMF. A suspension of <strong>[492-27-3]kynurenic acid</strong> (4.0 g, 0.021 m) in 45 ml DMF was added in portions. Gas evolution was noted. The suspension was heated to 60 C. for one hour and cooled to RT, after which ethyl bromoacetate (7.0 g, 0.042 mole) in 40 ml DMF was added dropwise. The reaction was stirred at room temperature overnight, then quenched into ice water and extracted 3x's with Et2 O. The organic layer was backwashed with H20 and sat. NaCl and dried over MgSO4.

Reference： [1]Patent: US5026700,1991,A

42
[ 343-65-7 ]
[ 492-27-3 ]

Yield	Reaction Conditions	Operation in experiment
		In the kidney, where kynurenine transaminase is present, it is possible that kynurenic acid is also formed from kynurenine.

Reference： [1]Patent: US5002963,1991,A
[2]Journal of Medicinal Chemistry,2009,vol. 52,p. 2786 - 2793

43
[ 492-27-3 ]
[ 4203-20-7 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium hydroxide; trichlorophosphate; In 1,4-dioxane; water;	(1) Phosphorus oxychloride (100 mL) was added to <strong>[492-27-3]kynurenic acid</strong> (25 g). The mixture was refluxed for 6 hr. The reactionmixture was concentrated under reduced pressure, and the residue was dissolved in 1,4-dioxane (100 mL). Aqueous ammonia (400 mL) was dropwise added thereto under ice-cooling. Water (500 mL) was added thereto, and the mixture was extracted with chloroform. The extract was washed with brine and concentrated under reduced pressure to give 4-chloroquinoline-2-carboxamide (27.3 g) as a black purple solid.

Reference： [1]Patent: EP1308439,2003,A1

44
[ 492-27-3 ]
[ 422-05-9 ]
[ 356-42-3 ]
C₁₆H₇F₁₀NO₄ [ No CAS ]

Reference： [1]Journal of Mass Spectrometry,2008,vol. 43,p. 782 - 790

45
[ 492-27-3 ]
[ 624-78-2 ]
[ 1010836-36-8 ]

Yield	Reaction Conditions	Operation in experiment
50%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 3h;	EXAMPLE 168 4-[2-tert-Butyl-1-(tetrahydropyran-4-ylmethyl)-1H-imidazol-4-yl]-N-ethyl-N-methylquinoline-2-carboxamide (Compound 168) Step 1; 4-Hydroxyquinoline-2-carboxylic acid (1.00 g, 5.29 mmol) was dissolved in DMF (10 mL), and N-ethylmethylamine (91 muL, 10.6 mmo1), WSC·HCl (2.03 g, 10.6 mmol), and HOBt·H2O (1.62 g, 10.6 mmol), were added thereto, and the mixture was stirred at room temperature for 3 hours. To the mixture, an aqueous sodium hydrogen carbonate solution was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol = 95/5) to give N-ethyl-4-hydroxy-N-methylquinoline-2-carboxamide (615 mg, 2.67 mmol, yield: 50%). Mass (m/e): 231 (M+H)+.

Reference： [1]Patent: EP2090570,2009,A1 .Location in patent: Page/Page column 89-90

46
[ 492-27-3 ]
N-((1s,4s)-4-aminocyclohexyl)-5-fluoro-2-(4'-hydroxy-2'-(morpholinomethyl)biphenyl-3-yloxy)nicotinamide dihydrochloride [ No CAS ]
N-((1s,4s)-4-(5-fluoro-2-(4'-hydroxy-2'-(morpholinomethyl)biphenyl-3-yloxy)nicotinamido)cyclohexyl)-4-hydroxyquinoline-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 41N-((ls,4s)-4-(5-fluoro-2-(4'-hydroxy-2'-(morpholinomethyl)biphenyl-3- yloxy)nicotinamido)cyclohexyl)-4-hydroxyquinoline-2-carboxamide To a solution of <strong>[492-27-3]4-hydroxyquinoline-2-carboxylic acid</strong> hydrate (38.2 mg, 0.20 mmol) in N- methyl-2-pyrrolidinone (2 mL) was added HOBt (37.2 mg, 0.24 mmol) and EDCI (38.8 mg, 0.20 mmol) the mixture was stirred for 10 min at RT. This mixture was then added to a solution of N-((l s,4s)-4-aminocyclohexyl)-5-fluoro-2-(4'-hydroxy-2'- (morpholinomethyl)biphenyl-3-yloxy Nicotinamide, dihydro chloride (120 mg, 0.20 mmol) and triethylamine (0.113 mL, 0.81 mmol) in N-methyl-2-pyrrolidinone (2 mL). The reaction mixture was stirred at RT overnight. A further aliquot of 0.5 eq of the acid, EDCI and HOBt was preformed and then added the reaction mixture. The mixture was diluted with -ImL water and purified using reverse phase prep HPLC (eluent = TFA(aq)/MeCN), the appropriate fractions were combined and evaporated to give an oil which on trituration with ether afforded the title compound. Yield: 23 mg.1H NMR (600 MHz, CD3OD) delta 8.48 (d, J = 7.0Hz, IH), 8.23 (dd, J = 8.2Hz, 0.9Hz, IH), 8.15 (d, J = 3.1Hz, IH), 8.11 - 8.07 (m, IH), 7.82 (d, J = 8.4Hz, IH), 7.77 - 7.73 (m, IH), 7.57 (t, J = 7.9Hz, IH), 7.46 (t, J = 7.6Hz, IH), 7.28 (dd, J = 8.1Hz, 2.2Hz, IH), 7.23 - 7.16 (m, 3H), 7.04 (d, J = 2.5Hz, IH), 6.92 (dd, J = 8.4Hz, 2.4Hz, IH), 6.73 (s, IH), 4.33 (s, 2H), 4.16 (s, IH), 4.06 - 3.98 (m, IH), 3.87 - 3.57 (m, 4H), 3.22 - 2.78 (m, 4H), 1.99 - 1.76 (m, 8H). MS: [M+H]+=692.2 (calc=692.2884) (MultiMode+)

Reference： [1]Patent: WO2009/144494,2009,A1 .Location in patent: Page/Page column 91

47
[ 492-27-3 ]
[ 100-39-0 ]
[ 1373835-84-7 ]

Yield	Reaction Conditions	Operation in experiment
		2-carboxy-4-hydroxyquinoline (5 g, 1.0 eq) was dissolved in 50 mL DMF. Cesium carbonate (20 g, 2.3 eq) was added to the solution and the resulting reaction mixture was heated at 50C for 20 minutes. Benzyl bromide (10g, 2. 1EQ) was added. The resulting reaction mixture was stirred at 50C for 1 hour. Then the reaction mixture was poured into 500 MLICE-WATER, the precipitate was collected by filtration, and dried in vacuo to afford 2- benzyloxycarbonyl-4-benzyloxyquinoline (9.1 g). 2-benzyloxycarbonyl-4-benzyloxyquinoline (9.0 g) was dissolved in 50 mL THF, and 2 N LIOH solution (20 mL) was added, and the resulting reaction mixture was stirred at ambient temperature for 2 hours. The solvent was then removed in vacuo, and the residue acidified by the addition of 2N NaHS04 to pH 3-4. The white precipitate was collected to afford 2-carboxy-4-benzyloxyquinoline (7.2 g), which was --USED-WITHOUT-FURTHER-PURIFICATION

Reference： [1]Patent: WO2004/52366,2004,A1 .Location in patent: Page 47

48
[ 478006-51-8 ]
[ 492-27-3 ]
[ 710335-35-6 ]

Yield	Reaction Conditions	Operation in experiment
		Alternatively, 2-CARBOXY-4-HYDROXYOXOQUINOLINE (640 mg, 3.2 mmol), EDCI (674 mg, 3.5 MMOL), and HOBT (525 mg, 3.5 MMOL) were combined in 20 mL CH2CI2 with triethylamine (0.67 mL, 4.8 mmol). The resulting reaction mixture was stirred at ambient temperature for 10 minutes, then 4-ETHOXYCARBONYL-1- (1-AMINO-3- (1, 1- dimethylethoxycarbonyl) propyl)-carbonylpiperazine (1.1 g, 3.3 MMOL) was added. The resulting mixture was stirred at ambient temperature for 2 hours. The reaction mixture was washed with water, 2N NAHS04, and brine, then concentrated in vacuo to afford an oil, which was purified by flash column chromatography on silica gel to afford 2- [1 S- (4- (ETHOXYCARBONYL) piperazin-1- YL) CARBONYL-3- (1, 1-DIMETHYLETHOXYCARBONYL) PROPYL] AMINOCARBONYL-4-HYDROXYQUINOLINE (1.28 G).

Reference： [1]Patent: WO2004/52366,2004,A1 .Location in patent: Page 48

49
[ 492-27-3 ]
[ 108-00-9 ]
2-(2-N,N-dimethyl-amino-ethylamino-1-carbonyl)-1H-quinolin-4-one hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%		0.40 g (2.13 mmol) of <strong>[492-27-3]kynurenic acid</strong> are dissolved in 30 ml of dimethylformamide (DMF), 0.28 g (2.13 mmol) of 1 -hydroxy benztriazole and 0.19 g (2.13 mmol) of N,N-dimethylethylene diamine are added. The mixture thus obtained is stirred at O0C for 30 minutes whereafter 0.4 ml (2.34 mmol) of N,N'-diisopropyl carbodiimide (DCI) are added. The mixture is allowed to warm up to room temperature and it is further stirred for 24 hours. After removing the solvent, the product is purified by column chromatography, using methanol as eluent.After evaporation the obtained free base is converted to a salt by using hydrochloric acid - ethanol- Et2O. 0,54 g (86 %); m.p.: 178-179 0C. 1H NMR (D2O); 3,00 (6H, s, N-CH3); 3,47 (2H, t, J = 5,8 Hz, CH2); 3,87 (2H, t, J = 5,7 Hz, CH2); 6,90 (IH, s, C3-H); 7,58 (IH, t, J = 7,2 Hz, Ar-H); 7,81- 7,86 (2H, m, Ar-H); 8,18 (IH, d, J = 8,1 Hz, Ar-H).

Reference： [1]Patent: WO2010/128345,2010,A1 .Location in patent: Page/Page column 8; 15; 16

50
[ 492-27-3 ]
[ 1256453-57-2 ]

Reference： [1]Organometallics,2010,vol. 29,p. 6051 - 6056

51
[ 492-27-3 ]
[ 106-95-6 ]
[ 1256453-63-0 ]

Reference： [1]Organometallics,2010,vol. 29,p. 6051 - 6056

52
vanadyl sulfate trihydrate [ No CAS ]
[ 492-27-3 ]
trans-[VO(4-hydroxyquinoline-2-carboxylate)2(H₂O)] [ No CAS ]

Reference： [1]Inorganic Chemistry,2011,vol. 50,p. 883 - 899

53
[ 492-27-3 ]
[ 765-30-0 ]
[ 1201581-86-3 ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 12h;	EXAMPLE 12The preparation of N-cyclopropyl-4-[(R)-1-(9H-purin-6-yl)pyrrolidin-2-yl-methoxy]quinoline-2-carboxamide (?A14?) is carried out analogously to the following scheme12.1 1 g of commercially available <strong>[492-27-3]4-hydroxyquinoline-2-carboxylic acid</strong> and 0.37 ml of commercially available cyclopropylamine are reacted at RT for 12 h in 50 ml of DMF together with 1.7 ml of N-methylmorpholine, 1 g of N-(3-di-methylaminopropyl)-N'-ethylcarbodiimide hydrochloride and 0.7 g of 1-hydroxy-benzotriazole. For work-up, the batch is poured into 50 ml of ethyl acetate and 50 ml of water. The organic phase is extracted with saturated KHSO4 solution, dried over magnesium sulfate and, after removal of the solvent, chromatographed on silica gel, giving 440 mg of colourless crystals; Rt.: 1.324 min; [M+H]+229.2.

Reference： [1]Patent: US2011/263561,2011,A1 .Location in patent: Page/Page column 23

54
[ 2922-83-0 ]
[ 492-27-3 ]

Reference： [1]Journal of Antibiotics,2011,vol. 64,p. 117 - 122

55
[ 492-27-3 ]
[ 139896-91-6 ]

Reference： [1]Patent: WO2012/6068,2012,A2

56
[ 492-27-3 ]
[ 1354965-44-8 ]

Reference： [1]Patent: WO2012/6068,2012,A2

57
[ 492-27-3 ]
[ 1354965-46-0 ]

Reference： [1]Patent: WO2012/6068,2012,A2

58
[ 492-27-3 ]
[ 1407188-92-4 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9589 - 9606

59
[ 492-27-3 ]
C₁₂H₁₀ClNO₃ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9589 - 9606

60
[ 492-27-3 ]
C₁₂H₁₀N₄O₃ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9589 - 9606

61
[ 492-27-3 ]
C₁₂H₁₀N₂O₃ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9589 - 9606

62
[ 492-27-3 ]
[ 1407189-03-0 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9589 - 9606

63
[ 492-27-3 ]
[ 1407189-07-4 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9589 - 9606

64
[ 492-27-3 ]
C₁₃H₁₃NO₄ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9589 - 9606

65
methyl (S)-3-(3-aminophenyl)-2-((tert-butoxycarbonyl)amino)propanoate [ No CAS ]
[ 492-27-3 ]
methyl 2-((tert-butoxycarbonyl)amino)-3-(3-(4-hydroxyquinoline-2-carboxamido)phenyl)propanoate [ No CAS ]

Reference： [1]ChemMedChem,2014,vol. 9,p. 2699 - 2707

66
[ 492-27-3 ]
[ 65615-90-9 ]
methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(4-hydroxyquinoline-2-carboxamido)phenyl)propanoate [ No CAS ]

Reference： [1]ChemMedChem,2014,vol. 9,p. 2699 - 2707

67
[ 492-27-3 ]
4-hydroxyquinoline-2-carboxylic-3-d acid [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 178 - 184

68
[ 109-99-9 ]
[ 492-27-3 ]
[ 125370-09-4 ]
6Ga⁽²⁺⁾*2C₄H₈O*4C₁₀H₅NO₃^(2-)*6C₇H₁₉Si₂^(1-)*2H⁽¹⁺⁾ [ No CAS ]

Reference： [1]Zeitschrift fur Anorganische und Allgemeine Chemie,2015,vol. 641,p. 253 - 260

69
[ 492-27-3 ]
[ 13325-10-5 ]
4-oxo-1,4-dihydroquinoline-2-carboxylic acid (4-hydroxybutyl)amide [ No CAS ]