[ CAS No. 486-74-8 ] {[proInfo.proName]}

Name: 486-74-8|Quinoline-4-carboxylic acid|98%
Brand: Ambeed
SKU: A820464
Price: 15.0 USD
Availability: InStock
Rating: 94 (29 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

2D 3D

Structure of 486-74-8 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 486-74-8 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 486-74-8 ]

SDS Specification

Alternatived Products of [ 486-74-8 ]

Product Details of [ 486-74-8 ]

CAS No. :	486-74-8	MDL No. :	MFCD00006782
Formula :	C₁₀H₇NO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VQMSRUREDGBWKT-UHFFFAOYSA-N
M.W :	173.17	Pubchem ID :	10243
Synonyms :	Cinchoninic acid (6CI,7CI,8CI);4-Carboxyquinoline

Calculated chemistry of [ 486-74-8 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	48.7
TPSA :	50.19 Å²

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) :	-7.03 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.31
Log Po/w (XLOGP3) :	0.46
Log Po/w (WLOGP) :	1.93
Log Po/w (MLOGP) :	0.23
Log Po/w (SILICOS-IT) :	1.82
Consensus Log Po/w :	1.15

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.71
Solubility :	3.4 mg/ml ; 0.0196 mol/l
Class :	Very soluble
Log S (Ali) :	-1.08
Solubility :	14.3 mg/ml ; 0.0827 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-3.07
Solubility :	0.147 mg/ml ; 0.000851 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.06

Safety of [ 486-74-8 ]

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 [ 486-74-8 ]

* 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 [ 486-74-8 ]
Downstream synthetic route of [ 486-74-8 ]

[ 486-74-8 ] Synthesis Path-Upstream 1~5

1
[ 491-35-0 ]
[ 4363-93-3 ]
[ 486-74-8 ]

Reference： [1] Synthetic Communications, 1996, vol. 26, # 9, p. 1681 - 1684

2
[ 7732-18-5 ]
[ 7758-99-8 ]
[ 486-74-8 ]
[ 580-18-7 ]

Reference： [1] Patent: US2764587, 1954, ,

3
[ 64-17-5 ]
[ 486-74-8 ]
[ 10447-29-7 ]

Reference： [1] Recueil des Travaux Chimiques des Pays-Bas, 1889, vol. 8, p. 218
[2] Chemische Berichte, 1938, vol. 71, p. 387,393
[3] Journal of the American Chemical Society, 1946, vol. 68, p. 1837,1838
[4] Proceedings of the Royal Society of London, Series B: Biological Sciences, 1938, vol. 125, p. 60,69
[5] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1988, p. 670 - 673[6] Khimiya Geterotsiklicheskikh Soedinenii, 1988, vol. 24, # 6, p. 819 - 821

4
[ 486-74-8 ]
[ 10447-29-7 ]

Reference： [1] Bulletin of the Chemical Society of Japan, 1987, vol. 60, # 8, p. 2891 - 2898

5
[ 486-74-8 ]
[ 15733-89-8 ]

Reference： [1] Chemische Berichte, 1879, vol. 12, p. 97
[2] Chemische Berichte, 1883, vol. 16, p. 2158

[ 486-74-8 ] Synthesis Path-Downstream 1~74

1
[ 491-35-0 ]
[ 486-74-8 ]

Reference： [1]Chemical Communications,2002,p. 180 - 181
[2]Recueil des Travaux Chimiques des Pays-Bas,1883,vol. 2,p. 14
[3]Journal of the American Chemical Society,1937,vol. 59,p. 524
[4]Justus Liebigs Annalen der Chemie,1958,vol. 613,p. 153,155, 162
[5]Justus Liebigs Annalen der Chemie,1958,vol. 613,p. 153,155, 162
[6]Justus Liebigs Annalen der Chemie,1958,vol. 613,p. 153,155, 162
[7]Patent: US1945067,1930,

2
[ 4363-93-3 ]
[ 6281-32-9 ]
[ 486-74-8 ]

Reference： [1]Archiv der Pharmazie,1959,vol. 292,p. 682,690
[2]Journal of the American Chemical Society,1946,vol. 68,p. 2568
[3]Journal of the American Chemical Society,1946,vol. 68,p. 2568

3
[ 2973-27-5 ]
[ 4363-95-5 ]
[ 486-74-8 ]

Reference： [1]Chemische Berichte,1912,vol. 45,p. 1806

4
[ 5467-57-2 ]
[ 486-74-8 ]

Reference： [1]Journal of the American Chemical Society,1946,vol. 68,p. 1837,1838
[2]Proceedings of the Royal Society of London. Series B, Biological sciences,1938,vol. 125,p. 60,69

5
[ 64-17-5 ]
[ 486-74-8 ]
[ 10447-29-7 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1889,vol. 8,p. 218
[2]Chemische Berichte,1938,vol. 71,p. 387,393
[3]Journal of the American Chemical Society,1946,vol. 68,p. 1837,1838
[4]Chemistry of Heterocyclic Compounds,1988,p. 670 - 673
Khimiya Geterotsiklicheskikh Soedinenii,1988,vol. 24,p. 819 - 821

6
[ 486-74-8 ]
[ 50821-72-2 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; In toluene; for 1h;Heating / reflux;	Example 134A Quinoline-4-carbonyl chloride A solution of 4-quinolinecarboxylic acid (Aldrich, 0.25 g, 1.4 mmol) in 5 mL of thionyl chloride was warmed to reflux and allowed to stir for 1 hour. The mixture was then cooled to ambient temperature and concentrated under reduced pressure. This material was dissolved in 10 mL toluene and concentrated under reduced pressure (3*) to afford the title compound.
	With thionyl chloride; for 1h;Heating / reflux;	A solution of 4-quinolinecarboxylic acid (Aldrich, 0.25 g, 1.4 mmol) in 5 mL of thionyl chloride was warmed to reflux and allowed to stir for 1 hour. The mixture was then cooled to ambient temperature and concentrated under reduced pressure. This material was dissolved in 10 mL toluene and concentrated under reduced pressure (3X) to afford the title compound
	With thionyl chloride; N,N-dimethyl-formamide; at 40℃; for 3h;	A suspension of quinoline 4-carboxylic acid (1.13 g, 6.53 mmol) and DMF (3 drops) in thionyl chloride (15 mL) was stirred at 40 °C for 3 h. Thionyl chloride was evaporated and the residue was dissolved in dry DCM (50 mL) and MeNHOMe*HCl (0.96 g, 9.8 mmol) and Et3N (2.7 mL, 19.6 mmol) was added. The mixture was stirred at 20 °C for 16 h. The resulting solution was diluted with DCM (100 mL) and washed with water (2 .x. 30 mL), washed with brine (30 mL), dried and the solvent evaporated. The residue was purified by column chromatography, eluting with EtOAc, to give amide 69 (1.36 g, 96percent) as soft solid

With thionyl chloride;N,N-dimethyl-formamide; at 40℃; for 3h;Product distribution / selectivity;

Example 1-106 7V-(3-Methylphenyl)-4-(4-quinolinyl)-l,3-thiazol-2-amine (192). [0398] 7V-Methyl-7V-(methyloxy)-4-quinolinecarboxamide (189). A suspension of quinoline 4-carboxylic acid (1.13 g, 6.53 mmol) and DMF (3 drops) in thionyl chloride (15 mL) was stirred at 40 0C for 3 h. Thionyl chloride was evaporated and the residue was dissolved in dry DCM (50 mL) and MeNHOMeetaCl (0.96 g, 9.8 mmol) and Et3N (2.7 mL, 19.6 mmol) was added. The mixture was stirred at 20 0C for 16 h. The resulting solution was diluted with DCM (100 mL) and washed with water (2 x 30 mL), washed with brine (30 mL), dried and the solvent evaporated. The residue was purified by column chromatography, eluting with EtOAc, to give amide 189 (1.36 g, 96percent) as soft solid: 1H NMR (CDCl3) delta 8.97 (d, J= 4.3 Hz, 1 H, H-2), 8.16 (d, J= 8.5 Hz, 1 H, H-5), 7.87 (d, J= 8.3 Hz, 1 H, H-8), 7.73-7.78 (m, 1 H, H-7), 7.56-7.62 (m, 1 H, H-6), 7.39 (d, J= 4.3 Hz, 1 H, H-3), 3.47 (s, 3 H, OCH3), 3.41 (s, 3 H, NCH3); MS m/z 216.4 (MH+, 100percent).

Reference： [1]Chemical Communications,2008,p. 4007 - 4009
[2]Chemische Berichte,1917,vol. 50,p. 1504
[3]Journal of Medicinal Chemistry,1992,vol. 35,p. 4893 - 4902
[4]Bulletin of the Chemical Society of Japan,1987,vol. 60,p. 2891 - 2898
[5]Journal of Medicinal Chemistry,1995,vol. 38,p. 3094 - 3105
[6]European Journal of Medicinal Chemistry,2004,vol. 39,p. 85 - 97
[7]Organic Letters,2000,vol. 2,p. 3735 - 3737
[8]Patent: US2008/58335,2008,A1 .Location in patent: Page/Page column 34
[9]Patent: WO2009/67613,2009,A1 .Location in patent: Page/Page column 92
[10]Journal of Medicinal Chemistry,2009,vol. 52,p. 4883 - 4891
[11]Angewandte Chemie - International Edition,2010,vol. 49,p. 1275 - 1277
[12]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 6122 - 6126
[13]ACS Medicinal Chemistry Letters,2010,vol. 1,p. 371 - 375
[14]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 3347 - 3356
[15]Angewandte Chemie - International Edition,2011,vol. 50,p. 10448 - 10452
[16]Journal of Medicinal Chemistry,2013,vol. 56,p. 220 - 240
[17]Organic Letters,2013,vol. 15,p. 1922 - 1925
[18]Chemistry - A European Journal,2014,vol. 20,p. 9902 - 9905
[19]Angewandte Chemie - International Edition,2017,vol. 56,p. 1877 - 1880
Angew. Chem.,2017,vol. 129,p. 1903 - 1906,4
[20]Patent: WO2009/114552,2009,A1 .Location in patent: Page/Page column 178

7
[ 486-74-8 ]
[ 13337-69-4 ]

Yield	Reaction Conditions	Operation in experiment
66%		<strong>[486-74-8]Quinoline-4-carboxylic acid</strong> (580 mg, 3.35 mmol) was dissolved in an aqueous potassium hydroxide solution (1 M, 10 mL). Nickel/aluminum amalgam (3 g) was added in portions over 1.5 hours. The heterogeneous mixture was stirred at room temperature for 48 hours. Upon completion, the reaction was filtered through Celite.(R). and washed with ethyl acetate. The pH of the aqueous layer was adjusted with concentrated hydrochloric acid to 4-5. Solid sodium chloride was added until the aqueous layer was saturated. The ethyl acetate layer was separated. The aqueous phase was extracted with ethyl acetate. The extracts were combined, washed with minimal brine, dried over sodium sulfate, filtered, and concentrated. l,2,3,4-Tetrahydro-quinoline-4-carboxylic acid was used without further purification (389 mg, 66percent). 1H-NMR (CDCl3) delta: 1.95 - 2.08 (m, IH), 2.22 - 2.37 (m, IH), 3.23 - 3.34 (m, IH), 3.39 - 3.49 (m, IH), 3.79 (dd, IH), 6.56 (d, IH), 6.69 (dd, IH), 7.07 (dd, IH), 7.17 (d, IH). MS m/z: 178 (M+l).
	With hydrogen;nickel; In methanol; at 20℃; under 3102.97 Torr; for 19h;	Example 31; N-(1-benzyl-1,2,3,4-tetrahydroquinolin-4-yl)-N'-1H-indazol-4-ylurea; Example 31A; 4.35 g (25.1 mmol) quinoline-4-carboxylic acid was added to 125 mL methanol and 8.7 g Raney nickel in a Parr shaker. The reactor was sealed and flushed with nitrogen, and then was pressurized with 60-psi hydrogen. The mixture was shaken at ambient temperature for 19 hours. After the reactor was flushed with nitrogen, the Raney nickel was filtered off and washed with methanol, and the filtrate was concentrated to provide 5.25 g of Example 31A.
	With sodium hydroxide;Raney nickel; In water;	Example 73; rac- 4-(lH-Imidazol-2-ylmethyl)-l,2,3,4-tetrahydro-quinoline; a) rac-1, 2,3,4- Tetrahvdro-quinoline-4-carboxylic acidrac- 1, 2,3,4- Tetrahydro-quinoline-4-carboxylic acid was prepared from quinoline-4- carboxylic acid by treatment with Raney nickel in aqueous sodium hydroxide according to the procedure described in Khimiya Geterotsiklicheskikh Soedinenii 1988, 77-9; brown <n="66"/>crystals; 1H-NMR (CDCl3): 2.04 (IH, m), 2.29 (IH, m), 3.24-3.46 (br m, 3 H, CH2N and NH), 3.77 (IH, t, CHCO2), 6.55 (IH, d, ArH), 6.67 (IH, dd, ArH), 7.04 (IH, dd, ArH), 7.15 (1H, d, ArH).

Reference： [1]Chemistry of Heterocyclic Compounds,1988,vol. 24,p. 65 - 67
Khimiya Geterotsiklicheskikh Soedinenii,1988,vol. 24,p. 77 - 79
[2]Patent: WO2006/91674,2006,A1 .Location in patent: Page/Page column 84
[3]Monatshefte fur Chemie,1881,vol. 2,p. 29
Monatshefte fuer Chemie,1882,vol. 3,p. 61 Anm. 2
[4]Patent: US2006/128689,2006,A1 .Location in patent: Page/Page column 21-22
[5]Patent: WO2007/85558,2007,A1 .Location in patent: Page/Page column 64-65
[6]Journal of Medicinal Chemistry,2013,vol. 56,p. 9897 - 9919

8
[ 486-74-8 ]
[ 15733-89-8 ]

Reference： [1]Chemische Berichte,1879,vol. 12,p. 97

9
[ 486-74-8 ]
[ 500534-95-2 ]

Reference： [1]Chemical Communications,2015,vol. 51,p. 15458 - 15461
[2]Monatshefte fur Chemie,1880,vol. 1,p. 845,846
[3]Monatshefte fur Chemie,1880,vol. 1,p. 845,846
[4]Journal of the American Chemical Society,1925,vol. 47,p. 2021

10
[ 486-74-8 ]
[ 91799-73-4 ]

Yield	Reaction Conditions	Operation in experiment
5.8 g (87%)	With thionyl chloride; In dichloromethane;	(a) 4-Quinolinecarboxylic acid chloride hydrochloride To 4-quinolinecarboxylic acid (5.0 g, 29.1 mmol) at 0° C. under argon was added thionyl chloride (20.0 ml, 0.27 mol). The reaction mixture was slowly warmed to room temperature and stirred for 1 hour. Dichloromethane (100 ml) was added and the reaction mixture was refluxed for 3 hours. The solvents were removed by distillation and the residue was dried at 130° C. in high vacuum to afford 5.8 g (87percent) of 4-quinolinecarboxylic acid chloride hydrochloride as a green crystals, m.p. 249°-251° C.

Reference： [1]European Journal of Medicinal Chemistry,1992,vol. 27,p. 977 - 984
[2]Chemische Berichte,1926,vol. 59,p. 1479,1482
[3]Patent: US5294612,1994,A

11
[ 2973-27-5 ]
[ 486-74-8 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1987,vol. 60,p. 2891 - 2898
[2]Chemische Berichte,1912,vol. 45,p. 1806
[3]Chemische Berichte,1912,vol. 45,p. 1806

12
[ 120-72-9 ]
[ 486-74-8 ]
[ 89391-04-8 ]

Yield	Reaction Conditions	Operation in experiment
	solid phase synthesis; Yield given. Multistep reaction;

Reference： [1]Hoemann, Michael Z.; Melikian-Badalian, Anita; Kumaravel; Hauske, James R. [Tetrahedron Letters, 1998, vol. 39, # 27, p. 4749 - 4752]

13
[ 7732-18-5 ]
[ 7758-99-8 ]
[ 486-74-8 ]
[ 580-18-7 ]

Reference： [1]Patent: US2764587,1954,

14
[ 486-74-8 ]
[ 215790-38-8 ]
trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolinecarboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 1878 - 1885

15
[ 486-74-8 ]
[ 497233-85-9 ]
quinoline-4-carboxylic acid (3-{4-[3-(7-chloro-quinolin-4-ylamino)-propyl]-piperazin-1-yl}-propyl)-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 542 - 557

16
[ 67-56-1 ]
[ 486-74-8 ]
[ 21233-61-4 ]

Yield	Reaction Conditions	Operation in experiment
93%	With thionyl chloride; at 0 - 60℃;Inert atmosphere;	[399] Into a 100-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed quinoline-4-carboxylic acid (1 g, 5.77 mmol, 1.00 equiv), methanol (25 mL), thionyl chloride (1.38 g, 2.00 equiv) was added at 0°C. The resulting solution was stirred overnight at 60 °C. After cooled to room temperature, the resulting mixture was concentrated under vacuum. This resulted in 1 g (93percent) of methyl quinoline-4-carboxylate as yellow oil. MS: (ES, m/z) [M+H]+: 188.

Reference： [1]Patent: WO2017/205296,2017,A1 .Location in patent: Paragraph 399
[2]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 4179 - 4188

17
[ 5319-77-7 ]
[ 486-74-8 ]
quinoline-4-carboxylic acid (5-methylsulfanyl-[1,3,4]thiadiazol-2-yl)-amide [ No CAS ]

Reference： [1]Medicinal Chemistry Research,2005,vol. 14,p. 260 - 273

18
[ 79611-76-0 ]
[ 486-74-8 ]
quinoline-4-carboxylic acid 3-(2-morpholin-4-yl-ethoxy)phenyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃; for 10h;	To a solution of quinoline-4-carboxylic acid (1.0 g) in methylene chloride (20 ml) were added 1,3- dicyclohexylcarbodiimide (1.2 g), 4-(dimethylamino)pyridine (0.07 g) and morpholinoethyl resorcinol (1.28 g), and stirring was conducted for 10 hrs at room temperature. The reaction solution was filtered, concentrated in a vacuum, and subjected to extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated in a vacuum, followed by purification through silica gel column chromatography to afford the object compound (1.6 g, 73percent).1H NMR(300 MHz, CDCl3) delta 9.01 - 6.54(m, 10H), 4.14(t, 2H), 3.72(t, 4H), 2.83ft 2H), 2.57ft 4H); <n="32"/>MS m/z 378(M+)

Reference： [1]Patent: WO2007/114672,2007,A1 .Location in patent: Page/Page column 30-31

19
[ 27627-84-5 ]
[ 486-74-8 ]
quinoline-4-carboxylic acid 2-(2-morpholin-4-yl-ethoxy)phenyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃; for 10h;	To a solution of quinoline-4-carboxylic acid (1.0 g) in methylene chloride (20 ml) were added 1,3- dicyclohexylcarbodiimide (1.2 g), 4-(dimethylamino)pyridine (0.07 g) and morpholinoethyl catechol (1.28 g), and stirring was conducted for 10 hrs at room temperature. The reaction solution was filtered, concentrated in a vacuum, and subjected to extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated in a vacuum, followed by purification through silica gel column chromatography to afford the object compound (1.3 g, 59percent).1H NMR(300 MHz, CDCl3) delta 9.12 - 7.05(m, 10H), 4.19(t, 2H), 3.50(t, 4H), 2.71(t, 2H), 2.40(t, 4H);MS m/z 378(M+)

Reference： [1]Patent: WO2007/114672,2007,A1 .Location in patent: Page/Page column 31

20
[ 56-57-5 ]
[ 486-74-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: hydrobromic acid / Heating 2: phosphorus trichloride 3: Heating 4: aq. base

Reference： [1]Ono, Isao; Hata, Norisuke [Bulletin of the Chemical Society of Japan, 1987, vol. 60, # 8, p. 2891 - 2898]

21
[ 486-74-8 ]
[ 10447-29-7 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1987,vol. 60,p. 2891 - 2898

22
[ 15733-89-8 ]
[ 486-74-8 ]

Reference： [1]Proceedings of the Royal Society of London. Series B, Biological sciences,1938,vol. 125,p. 60,69
[2]Journal of the American Chemical Society,1946,vol. 68,p. 1837,1838

23
[ 486-74-8 ]
[ 515881-16-0 ]
4-[[4-[4-[(Z)-(4-bromophenyl)(ethoxyimino)methyl]-1-piperidinyl]-4-methyl-1-piperidinyl]carbonyl]quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; HATU; In DMF (N,N-dimethyl-formamide); at 20℃; for 16h;	To a solution OF 4- [ (Z)- (4-BROMOPHENYL) (ethoxyimino) METHYL]-1- (4-METHYL-4- piperidinyl) piperidine (240 mg, 0.59 MMOL), quinoline-4-carboxylic acid (112 mg, 0.64 MMOL) and Et3N (119 mg, 1. 18 MMOL) in DMF (2 mL), HATU (290 mg, 0.76 MMOL) was added at room temperature. After 16 h, the reaction mixture was poured into ice water, and the solid was collected by filtration. Further purification by flash chromatography afforded title compound.'H NMR (DMSO-d6) 8 0.9 (s, 3H), 1. 18 (t, 3H), 1.22-1. 85 (m, 7H), 1. 98-2. 18 (m, 3H), 2.39 (m, 1H), 2.75 (m, 1 H), 2.96 (m, 2H), 3.31 (q, 1 H), 3.50 (q, 1H), 4.04 (q, 2H), 4.26 (m, 1 H), 7.09 (m, 2H), 7.28 (m, 1H), 7.5 (m, 2H), 7.58 (q, 1H), 7.71-7. 85 (m, 2H), 8.13 (d, 1H), 8.92 (d, 1H).

Reference： [1]Patent: WO2004/113323,2004,A1 .Location in patent: Page 39

24
[ 305794-41-6 ]
[ 486-74-8 ]
4-[[4-[4-[(4-bromophenyl)(2-pyridinyloxy)methyl]-1-piperidinyl]-4-methyl-1-piperidinyl]carbonyl]quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; HATU; In DMF (N,N-dimethyl-formamide); at 20℃; for 16h;	To a solution OF 4- [ (4-BROMOPHENYL) (2-PYRIDINYLOXY) METHYL]-1- (4-METHYL-4- piperidinyl) piperidine (220 mg, 0.5 MMOL), quinoline-4-carboxylic acid (110mg, 0.64 MMOL), and Et3N (192 mg, 1.9 MMOL) in DMF (5 mL) was added HATU (260 mg, 0.68 MMOL) at room temperature. After 16 h the reaction mixture was poured into ice water. The solid was collected by filtration, dissolved in CH2CI2, and dried over NA2SO4. Concentration and purification by flash chromatography (CH2CI2-MEOH, 95: 5 to 9: 1) afforded the title compound as a light yellow POWDER. HNMR (CDCI3, 400MHZ) : LC-MS. 598 (M+). H NMR (CDCL3) No. 0.91 (s, 3H), 1.16-2. 14 (m, 11H), 2.74 (m, 1 H), 2.96 (m, 2H), 3.30 (m, 1H), 3.56 (m, 1 H), 4.06 (q, 2H), 4.24 (m, 1H), 5.80 (m, 1H), 6.75 (m, 2H), 7.25 (m, 1H), 7.30 (d, 1H), 7.42 (m, 2H), 7.50-7. 65 (m, 2H), 7.75 (m, 1H), 7.85 (m, 1H), 8. 05 (m, 1H), 8.15 (d, 1H), 8.95 (d, 1H).

Reference： [1]Patent: WO2004/113323,2004,A1 .Location in patent: Page 53

25
[ 433920-55-9 ]
[ 486-74-8 ]
C₅₄H₆₈N₆O₁₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%		[0124] To the solution of compound of Example 1 (120 mg, 0.136 mmol), catalytic amount of dimethylaminopyridine and 4-quinolinecarboxylic acid (50 mg, 0.29 mmol) in CH2Cl2 (2 mL) was added 1,3-dicyclohexylcarbodiimide (120 mg, 0.58 mmol). The reaction was stirred at room temperature for 24 h before being diluted with methanol (5 mL) and stirred for another 24 h. The solvent was then removed and the residue was dissolved in ethyl acetate (50 mL). The resulting organic solution was washed with sat. aq. NaHCO3 and brine, and dried over MgSO4, and concentrated. Purification by chromatography (silica gel, 94:6:0.3 dichloromethane/methanol/conc. NH4OH) yielded 43 mg (32percent) of the title compound. MS 993 (M+H)+.

Reference： [1]Patent: US2004/18994,2004,A1 .Location in patent: Page/Page column 20

26
[ 486-74-8 ]
[ 864674-12-4 ]

Yield	Reaction Conditions	Operation in experiment
100%		Example 36; Synthesis of l-quinolin-4-yl-ethanone; [0135] Commercially available 4-quinolinecarboxylic acid was converted to the Weinreb amide in 100 percent yield. The Weinreb amide was converted to 4-acetylquinoline by reaction with methylmagnesium iodide in 50 percent yield.

Reference： [1]Patent: WO2005/84439,2005,A1 .Location in patent: Page/Page column 42-43
[2]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 3347 - 3356
[3]Patent: WO2009/114552,2009,A1

27
trans-3-(2-(1-(4-amino)cyclohexyl)ethyl)-2,3,4,5-tetrahydro-1H-3-benzazepine [ No CAS ]
[ 486-74-8 ]
trans-3-(2-(1-(4-(4-quinolinyl)carboxamido)cyclohexyl)ethyl)-2,3,4,5-tetrahydro-1H-3-benzazepine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride;benzotriazol-1-ol; In dichloromethane; for 16h;	A mixture of the appropriate trans-2- (2- (1- (4-amino) cyclohexyl) ethyl)-2, 3,4, 5- tetrahydro-1 H-3-benzazepine (0.35 mmol), the appropriate acid (0.35 mmol), 1- ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.35 mmol), 1- hydroxybenzotriazole (catalytic amount) and dichloromethane (5ml) was shaken for 16h. Saturated sodium bicarbonate (4ml) was then added and the mixture shaken for 0.25h. Chromatography of the organic layer on silica with 50-100percent ethyl acetate in hexane and 0-10percent methanol in ethyl acetate gradient elution gave the title compounds.

Reference： [1]Patent: WO2005/94835,2005,A1 .Location in patent: Page/Page column 37

28
[ 110-89-4 ]
[ 95753-56-3 ]
[ 486-74-8 ]
4-[[(4-quinolinyl)carbonyl]amino]-L-phenylalanine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one;	Example 63 Synthesis of 4-[(4-Quinolinylcarbonyl)amino]-L-phenylalanine on Wang Resin A 250 mL cylindrical glass vessel equipped with a coarse glass frit was charged with <strong>[95753-56-3]4-amino-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-phenylalanine</strong> (10 g) obtained in Example 62 and a solution prepared from quinoline-4-carboxylic acid (5.2 g, 30 mmol), BOP (13.75 g, 30 mmol) and diisopropylethylamine (6.8 mL) in 70 mL of N-methylpyrrolidinone. The slurry was agitated for 4 hr. The mixture was filtered and washed with dichloromethane (2100 mL), methanol (2100 mL) and dimethylformamide (2100 mL). To the washed resin was added a solution of 25% piperidine in N-methylpyrrolidinone (80 mL), the mixture was agitated at room temperature for 20 minutes and filtered. The process was repeated and the resulting slurry was filtered and washed with dichloromethane (2100 mL), methanol (2100 mL) and dimethylformamide (2100 mL). Filtration afforded 4-[(4-quinolinylcarbonyl)amino]-L-phenylalanine on Wang resin suitable for use in the next step.
	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine;	Example 37 Synthesis of 4-[[(4-quinolinyl)carbonyl]amino]-L-phenylalanine on Wang resin A 250 mL cylindrical glass vessel equipped with a coarse glass frit was charged with <strong>[95753-56-3]4-amino-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-phenylalanine</strong> on Wang resin (10 g) obtained in Example 36 and a solution prepared from quinoline-4-carboxylic acid (5.2 g, 30 mmol), BOP (13.75 g, 30 mmol) and diisopropylethylamine (6.8 mL) in 70 mL of NMP. The slurry was agitated for 4 hours. The mixture was filtered and washed with dichloromethane (2100 mL), methanol (2100 mL) and dimethylformamide (2100 mL). To the washed resin was added a solution of 25% piperidine in NMP (80 mL), the mixture was agitated at room temperature for 20 minutes and filtered. The process was repeated and the resulting slurry was filtered and washed with dichloromethane (2100 mL), methanol (2100 mL) and dimethylformamide (2100 mL). Filtration afforded 4-[[(4-quinolinyl)carbonyl]amino]-L-phenylalanine on Wang resin suitable for use in the next step.

Reference： [1]Patent: US6455550,2002,B1
[2]Patent: US6229011,2001,B1

29
[ 486-74-8 ]
[ 220876-23-3 ]
[ 220876-24-4 ]

Yield	Reaction Conditions	Operation in experiment
75%	With sodium hydroxide; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In methanol; ethanol; water; ethyl acetate; N,N-dimethyl-formamide;	Example 27 Synthesis of N-[(1-Phenylcyclopentyl)carbonyl]-4-[(4-quinolinylcarbonyl)amino]-L-phenylalanine Sodium Salt To a solution of 4-amino-N-[(1-phenylcyclopentyl)carbonyl]-L-phenylalanine methyl ester (81 mg, 0.2 mmol) and 4-quinolinecarboxylic acid (43.3 mg, 0.25 mmol) in 1 nL of DMF was added HBTU (95 mg, 0.25 mmol) and diisopropylethylamine (65 muL, 0.5 mmol) at room temperature. The mixture was then stirred at this temperature for overnight. The reaction was then diluted with 15 mL of ethyl acetate and was washed with water (2 mL), saturated NaHCO3 (22 mL) and saturated brine (22 mL). The solution was dried (MgSO4) and concentrated. The residue was hydrolyzed with 0.5 mL of 1N NaOH in 5 mL of ethanol at 25° C. overnight. The crude product was purified by passing through an open C-18 column eluding with water (200 mL), 30percent methanol in water (200 mL), 40percent methanol in water (200 mL) and pure methanol (200 mL). The fractions containing product were concentrated and lyophilized to give N-[(1-phenylcyclopentyl)carbonyl]-4-[(4-quinolinylcarbonyl)amino]-L-phenylalanine sodium salt (79.5 mg, 75percent), HR-FABMS: obs. mass, 530.2056. Calcd. mass, 530.2058.

Reference： [1]Patent: US6455550,2002,B1

30
(2R,4S)-2-benzyl-1-(3,5-bis-trifluoromethyl-benzoyl)-4-piperidineamine [ No CAS ]
[ 68641-49-6 ]
[ 486-74-8 ]
(2R,4S)-N-[1-(3,5-bis-trifluoromethyl-benzoyl)-2-benzyl-piperidin-4-yl]-quinoline-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane;	EXAMPLE 1 (2R,4S)-N-[1-(3,5-Bis-trifluoromethyl-benzoyl)-2-benzyl-piperidin-4-yl]-quinoline-4-carboxamide 2.95 g (11.6 mmol) of bis(2-oxo-3-oxazolidinyl)phosphinic acid chloride are added at 0 C. to a solution of 4.16 g (9.67 mmol) of (2R,4S)-2-benzyl-1-(3,5-bis-trifluoromethyl-benzoyl)-4-piperidineamine [EP 532 456 A1, Example 38 f], 1.84 g (10.6 mmol) of quinoline4-carboxylic acid and 3 ml (21.3 mmol) of triethylamine in 30 ml of methylene chloride and the ice bath is removed after 10 minutes. The reaction mixture is stirred for 4 hours at room temperature and then diluted with methylene chloride. The organic phase is extracted with aqueous 10% citric acid and with 1 N potassium carbonate solution, washed with brine, dried over magnesium sulfate and concentrated to dryness by evaporation.

Reference： [1]Patent: US5965562,1999,A

31
[ 486-74-8 ]
[ 21233-61-4 ]

Yield	Reaction Conditions	Operation in experiment
98.6%	In ethyl acetate;	Step 1 Method was as described for Example 36, Step 1, but using quinoline-4-carboxylic acid. The crude reaction mixture was chromatographed on silica gel using ethyl acetate as a eluant to obtain quinoline-4-carboxylic acid methylester (28.6 g, 98.6percent) as a oil.

Reference： [1]Patent: US5331006,1994,A

32
[ 486-74-8 ]
[ 121689-22-3 ]
[ 157915-10-1 ]

Yield	Reaction Conditions	Operation in experiment
	With nitric acid In sulfuric acid	8 (1R,5S,6S,8R,2'S,4'S)-2-(2-(4-Carboxyquinol-8-ylcarbamoyl)pyrrolidin-4-ylthio)-6-(1-hydroxyethyl)-1-methylcarbapenem-3-carboxylic Acid Disodium Salt The starting material was prepared as follows: To a suspension of 4-carboxyquinoline (5 g; 28.9 mM) in concentrated sulphuric acid (10 ml) was added, at 65° C., fuming nitric acid (9 ml) and concentrated sulphuric acid (9 ml). After stirring at 75° C for 30 minutes, the mixture was poured onto ice; the pH adjusted to pH3 and the resulting precipitate filtered and dried to give a mixture of 4-carboxy-8-nitroquinoline and 4-carboxy-5-nitroquinoline which was not separated (4.4 g; 70%). NMR (DMSO-d6): 8 7.97-8.03 (m, 2H); 8.37 (d, 1H); 8.47 (d,! H); 9.19 (d, 1H).

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - US5441949, 1995, A

33
[ 541-41-3 ]
[ 486-74-8 ]
[ 87-25-2 ]
[ 108890-73-9 ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium carbonate; In water; acetone;	Preparation of Ethyl-N-ethoxycarbonyl-o-aminobenzoate 2 To an ice cooled solution of ethyl-o-aminobenzoate 1 (33 g, 0.2 mole) in acetone (270 ml) was added with stirring an ice cooled solution of potassium carbonate (36.7 g, 0.27 mole) in water (214 ml) followed by addition of ethyl chloroformate (43 g, 0.4 mole). Stirring was continued at 0° C. for 11/2 hour and at 25° C. for 2 hours. The mixture was poured in water (300 ml) and extracted with three 300 ml portions of ether. The combined and dried (MgSO4) ether phases were evaporated in vacuo to give pure 2 (46.7 g, 98percent). The product was recrystallized (EtOH, H2 O) to give colorless crystals, mp <40° C. (Calc. for C12 H15 NO4: C 60.75; H 6.37; N 5.90). (Found C 60.75; H 6.29; N 5.85) 1 H NMR (CDCl3) delta= 1.3 (3H, t, J=7 Hz) 1.4 (3H, t, J=7 Hz) 4.2 (2H, q, J=7 Hz) 4.3 (2H, q, J=7 Hz) 6.9-8.5 (4H, AA'BB'). IR (CCl4): 3300(m), 2980(m), 1735(s), 1690(s), 1600(s), 1510(w), 1450(s).

Reference： [1]Patent: US4952573,1990,A

34
Al₂ O₃ [ No CAS ]
[ 486-74-8 ]
[ 13337-72-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	In acetic acid;	EXPERIMENTAL SECTION A solution of 4-quinoline carboxylic acid (1.5 g., 8.6 mmoles) in acetic acid (30 ml) containing 5percent Rh/Al2 O3 (400 mg) was reduced (4.2 kg, 85° C.) in a steel bomb for 15 hours. After cooling, the catalyst was filtered and the solvent was evaporated to dryness. The residue was triturated with EtOH/Et2 O (50/50), filtered and washed with a minimum of Et2 O to give pure 4-decahydroquinoline carboxylic acid (1.4 g, 90percent) as white crystals, mp >300° C., see Burckhardt, Helferick, L. Wissel, J. Prak. Chim. 39 (1966). An analytical sample of its hydrochloride salt was recrystallized in acetonitrile/water. (Found: C 54.19; H 8.62; N 6.33. Calc. for C10 H18 ClNO2: C 54.66 H 8.26; N 6.38). 1 H NMR 400 MHz (H2 O) delta=1.3-1.5 (4H, m) 1.67-1.76(1H,m) 1.82-2.04 (5H, m) 2.29-2.4 (1H, m) 2.62-2.7 (1H, d t) 3.01-3.17 (1H, m) 3.46-3.57 (2H,m) 7.89 (1H, broad s, exchangeable D2 O) 8.29 (1H broad s, exchangeable D2 O).

Reference： [1]Patent: US4952573,1990,A

35
methyl 3-(5-[1,2,3,6-tetrahydropyridin-4-yl]pyridin-2-yl)-N-(2,6-dichlorobenzoyl)-L-alaninate dihydrochloride [ No CAS ]
[ 486-74-8 ]
N-(2,6-dichlorobenzoyl)-3-[1'-(quinolin-4-ylcarbonyl)-1',2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-L-alanine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%		DIEA (51 mul, 0.29 mmol), 4-quinoline carboxylic acid (33 mg, 0.19 mmol) and TBTU (74 mg, 0.23 mmol) were added to a solution of methyl 3-(5-[l,2,3,6- tetrahydropyridin-4-yl]pyridin-2-yl)-N-(2,6-dichlorobenzoyl)-L-alaninate (83 mg, 0.19 o mmol) in DMF (2 ml). The solution was stirred at room temperature for 4 hours. A solution of 2nu LiOH (210 mul, 0.42 mmol) was added. After stirring overnight, the crude mixture was filtered and purified by reverse phase chromatography using a gradient of acetonitrile in water containing ammonium carbonate (4g/l). After evaporation and trituration in methylene chloride/ether, the title compound was obtained as a white solid s (33 mg, 61percent); 1H NMR spectrum fDMSO-d + CD3COOD, 500 MHz): presence of 2 rotamers (nearly 50/50) 2.35 (bs, IH), 2.71 (bs, IH), 3.09 (dd, IH), 3.29 (dd, IH), 3.37 (bs, IH), 3.67-4.60 (bs, 4H), 4.96 (dd, IH), 6.04 (bs, 0.5H), 6.39 (bs, 0.5H), 7.29 (d, IH), 7.34- 7.44 (m, 3H), 7.50-7.59 (m, IH), 7.62-7.89 (m, 4H), 8.10-8.17 (m, IH), 8.56-8.62 (m, IH), 8.97-9.03 (m, IH); Mass spectrum (M+H)+ = 575.

Reference： [1]Patent: WO2007/60409,2007,A1 .Location in patent: Page/Page column 98

36
[ 10025-74-8 ]
[ 486-74-8 ]
Dy⁽³⁺⁾*3C₁₀H₆NO₂^(1-)*2H₂O [ No CAS ]

Reference： [1]Journal of Inorganic and Nuclear Chemistry,1977,vol. 39,p. 599 - 605

37
trans-4-{2-[4-(4-fluorophenoxy)-piperidin-1-yl]-ethyl}-cyclohexylamine trifluoroacetate [ No CAS ]
[ 486-74-8 ]
quinoline-4-carboxylic acid trans-(4-{2-[4-(2-chloro-4-fluoro-phenoxy)-piperidin-1-yl]-ethyl}-cyclohexyl)-amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54.9%		11.5 <strong>[486-74-8]Quinoline-4-carboxylic acid</strong> trans(4-{2[4-(2-chloro-4-fluoro-phenoxy)-piperidin-1-yl]-ethyl}-cyclohexyl)-amide The title compound was prepared as follows. <strong>[486-74-8]Quinoline-4-carboxylic acid</strong> (0.020 g, 0.115 mmol), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyl uronium tetrafluoroborate (0.035 g, 0.106 mmol) and (0.05 mL, 0.318 mmol) of N-ethyldiisopropylamine were stirred in 0.5 mL of dimethylformamide (DMF) for 0.5 h at room temperature and Trans-4-{2-[4-(4-Fluoro-phenoxy)-piperidin-1-yl]-ethyl}-cyclohexylamine; trifluoro-acetic acid salt (0.050 g, 0.106 mmol) was added. The mixture was stirred for 12 hours at room temperature. The mixture was concentrated to dryness and the residue was taken up on methanol and purified with preparative HPLC on reversed phase eluding with acetonitrile/water. The combined product fractions were evaporated under reduced pressure to yield 0.054 g of a off-white solid (0.101 mmol, 54.9percent). MS (m/e): 510.2 (M+H+).

Reference： [1]Patent: US2008/103174,2008,A1 .Location in patent: Page/Page column 16-17

38
[ 486-74-8 ]
[ 141104-65-6 ]
[ 1092447-44-3 ]

Yield	Reaction Conditions	Operation in experiment
59%	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃;	EXAMPLE 49; 2-[fOuinoline-4-carbonyl)-aminol-indan-2-carboxylic acid ethyl ester (49):To a solution of quinoline-4-carboxylic acid (301mg, 1.74mmol), 2-amino-indan-2-carboxylic acid ethyl ester (357mg, 1.74mmol), HATU (992mg, 2.61mmol) in anhydrous DMF (8mL) is added DIPEA (431muL, 2.61mmol). The resulting solution is stirred at RT overnight. After the removal of DMF in vacuo, the residue is dissolved in EtOAc (4OmL) and washed with water (1 x 1OmL) and brine (2 x 1OmL). The organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The residue is purified by flash column chromatography (12Og silica gel, gradient elution: 5-70percent EtOAc in heptane) to give a pure product (49) as a pale yellow solid (370mg, 59percent).1H NMR (CDCl3, 300MHz): delta 1.34(t, 3H), 3.48(d, 2H), 3.82(d, 2H), 4.34(q, 2H), 6.86(s, IH), 7.21-7.29(m, 5H), 7.51-7.56(m, IH), 7.65-7.71(m, IH), 7.98(d, IH), 8.18(d, IH), 8.73(d, IH)73 <n="75"/>LC/MS (ES+) m/z = 361.14

Reference： [1]Patent: WO2008/151211,2008,A1 .Location in patent: Page/Page column 73-74

39
[ 486-74-8 ]
[ 221164-26-7 ]
ethyl 3,4-dihydro-3-oxo-7-((4-(N-(4-quinolyl)carbamoyloxy)methyl)-imidazole-1-yl)-6-trifluoromethylquinoxaline-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%		To a solution of quinoline-4-carboxylic acid (182 mg, 1.05 mmol) in benzene (5 ml) were added diphenylphosphoryl azide (226 mul, 1.05 mmol) and triethylamine (146 mul, 1.05 mmol), and the mixture was refluxed for 3 hours . To this was added a solution of the compound in Example 81 (200 mg, 523 mumol) in N,N-dimethylformamide (1 ml), and the mixture was refluxed further for 2 hours. Ethyl acetate was added to the reaction mixture, which was washed with brine, then dried over anhydrous magnesium sulfate, and solvent was distilled off. The residue obtained was purified by means of silica gel column chromatography [methylene chloride-ethanol [30:1 7:1)] to obtain 188 mg of ethyl 3,4-dihydro-3-oxo-7-((4-(N-(4-quinolyl)carbamoyloxy)methyl)-imidazole-1-yl)-6-trifluoromethylquinoxaline-2-carboxylate as yellow powder. Yield 65percent. To a solution of the ethyl ester (150 mg, 272 mumol) obtained in ethanol (3 ml) were added 1N aqueous solution of lithium hydroxide (950 mul, 950 mumol) and water (3 ml), and the mixture was stirred for 1.5 hours at 50° C. After cooling, ice water was added and the insolubles were filtered off. After dissolved these by adding 3N hydrochloric acid, the insolubles were filtered off. The filtrate was purified with synthetic adsorbent Sepabeads.(R). SP850 [water-acetonitrile (20:1-->5:1)] and recrystallized from water to obtain 10.3 mg of the title compound as light brown powder. Yield 7percent. mp 239-241° C. (decomposition). HR-FAB-:523.0975 (-0.2 mmu).

Reference： [1]Patent: US6348461,2002,B1 .Location in patent: Page column 121

40
[ 486-74-8 ]
4-[4-[1-(4-bromophenyl)ethenyl]-1-piperidinyl]-4-methyl-1-piperidinecarboxylic acid 1,1-dimethylethyl ester [ No CAS ]
4-[[4-[4-[1-(4-bromophenyl)ethenyl]-1-piperidinyl]-4-methyl-1-piperidinyl]carbonyl]quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a stirred solution of 4- [4- [1- (4-bromophenyl) ethenyl]-4-piperidinyl] 4-methyl-1- piperidinecarboxylic acid, dimethylethyl ester (51 mg, 0.11 MMOL) in CH2CI2 (2 mL) was added TFA (1 mL) at room temperature. After 2 h, the reaction was concentrated in vacuo and dried over vacuum. The crude product was dissolved in DMF (2 mL), then 4-QUINOLINECARBOXYLIC acid (21 mg, 0.12 MMOL), Et3N (22 mg, 0. 22 MMOL), and HATU (55 mg, 0.14 MMOL) was added at room temperature. After 16 h the mixture was poured into ice water (10 mL), and extracted with CH2CI2 (3x10 mL). The organic phase was dried over NA2SO4, and concentrated in vacuo. The crude product was purified by preparative TLC to afford the title compound. MS: 518 (M+). H NMR (CDCl3, 400MHz) 6 0.93 (d, 3H), 1.1-1. 62 (m, 4H), 1.62-1. 9 (m, 3H), 1.98-2. 22 (m, 3H), 2.24-2. 42 (m, 1H), 2.7-2. 88 (m, 1H), 2.9-3. 1 (m, 1H), 3.24-3. 42 (m, 1H), 3.5-3. 7 (m, 1H), 4.17- 4.4 (m, 1H), 5.0-5. 1 (s, 1H), 5.1-5. 22 (s, 1H), 7.14-7. 23 (m, 2H), 7.28-7. 36 (m, 1H), 7.4-7. 48 (m, 2H), 7.54-7. 66 (m, 1H), 7.72-7. 9 (m, 2H), 8.1-8. 2 (d, 1H), 8.9-9. 0 (m, 1H).

Reference： [1]Patent: WO2004/113323,2004,A1 .Location in patent: Page 54; 55

41
[ 305794-90-5 ]
[ 486-74-8 ]
4-[[4-[4-[(4-bromophenyl)(hydroxy)methyl]-piperidin-1-yl]-4-methylpiperidin-1-yl]carbonyl]quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a stirred solution OF 4- [4- (4-BROMOPHENYL) HYDROXYMETHYL]-1-PIPERIDINYL]-4-METHYL-1- piperidinecarboxylic acid 1, 1-diemthylethyl ester (1.03 g, 2.2 MMOL) in CH2CI2 (10 ML) was added TFA at room temperature. After 2 h the reaction mixture was concentrated in vacuo, and dried under vacuum. The product was dissolved in DMF (10 mL), and quinoline-4-carboxylic acid (450mg, 2. 6MMOL), Et3N (1. 0mL, 7. 2MMOL), and HATU (1. 1G, 2.9 MMOL) was added at room temperature. After 16 h, the reaction mixture was poured into ice water while stirring vigorously. The solid was collected by filtration, and was re-dissolved in CH2CI2 AND dried over NA2SO4. Concentration and purification by flash chromatography (CH2CI2-MEOH, 100: 1 to 100: 2 to 100: 4) afforded the title compound as a brown powder. MS: 523.1 (M++1). TH NMR (CD3) No. 0.92 (s, 3H), 1.27-2. 14 (m, 10H), 2.72-3. 00 (m, 3H), 3.33 (m, 1H), 3.60 (m, 1H), 4.21 (m, 1H), 4.38 (m, 1H), 7.19 (m, 2H), 7.31 (m, 1H), 7. 48 (m, 2H), 7.62 (m, 1H), 7.77-7. 86 (m, 2H), 8.15 (br. d, 1 H), 8.94 (m, 1 H).

Reference： [1]Patent: WO2004/113323,2004,A1 .Location in patent: Page 52

42
[ 1238071-99-2 ]
[ 486-74-8 ]
[ 1238070-08-0 ]

Yield	Reaction Conditions	Operation in experiment
68%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20℃; for 20h;	d) Quinoliotane-4-carboxylic acid ((S)-3-(benzoyl-methyl-amiotano)-4-phenyl-butyl]-amiotade N-((S)-3-Amino-1-benzyl-propyl)-N-methyl-benzamide (100mg, 0.35 mmo.) , quinoline-4- carboxylic acid (74 mg, 0 43 mmol), HOBt (65 mg, 0.43 mmol). EDC x HCI (102 mg, 0.53 mmo.) and tpiethylamine (143 mg, 1.42 mmol) were dissolved in DCM (10 ml) and stirred at rt for 20 h, The mixture was diluted with EtOAc, washed with NaHCO3- and NaCI-soln , dried (Na2SO4), filtered and concentrated The crude product was purified by chromatography (Flashrnaster, DCM to DCM:MeOH 97:3 over 20 mm ) to yield 105 mg (68percent) of the title compound as white solid. [1 H-NMR (DMSO, 600 MHz) 8 97-8.95 (m, 1 H)1 8.78/8 72 (t, 1 H), 8.17-7.02 (m, 14 H), 6.62 (d, 1H), 5 01/3 74 (br s. 1 H), 3 42-3 35/3.15-3 10 (m, 2H). 2 98- 2.72 (m, 2H), 2.99/2.68 (s, 3H), 2 00-1.77 (m, 2H), LCMS Rt6 = 3 007 mm, (M+Hf ~ 438 2]

Reference： [1]Patent: WO2010/86366,2010,A1 .Location in patent: Page/Page column 44; 45

43
(1RS,2SR)-1-(4-fluorophenyl)-1-hydroxy-3-(4-(trifluoromethyl)phenyl)-2-propylamine hydrochloride [ No CAS ]
[ 486-74-8 ]
N-((1RS,2SR)-2-(4-fluorophenyl)-2-hydroxy-1-((4-(trifluoromethyl)phenyl)methyl)ethyl)-4-quinolinecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%		To a solution of 4-quinolinecarboxylic acid (111 mg, 0.64 mmol) in tetrahydrofuran (5 ml) were added oxalyl chloride (0.11 ml, 1.72 mmol) and N,N-dimethylformamide (0.01 ml), and the mixture was stirred at room temperature for 30 min. The reaction solution was evaporated under reduced pressure. To a solution of the residue in ethyl acetate (5 ml) were added (1RS,2SR)-1-(4-fluorophenyl)-1-hydroxy-3-(4-(trifluoromethyl)phenyl)-2-propylamine hydrochloride (150 mg, 0.43 mmol) and saturated aqueous sodium hydrogen carbonate (5 ml) and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (50 ml), and extracted with ethyl acetate (50 ml.x.2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate) and recrystallized from ethyl acetate-hexane to give the title compound (63 mg, 32percent). mp! 227-228°C IR nu maxKBrcm-1: 1644, 1508, 1331. Anal. Calcd for C26H20F4N2O2*0.5H2O: C, 65.41; H, 4.43; N, 5.87 Found: C, 65.31; H, 4.68; N, 5.61.1H-NMR (CDCl3)delta: 2.76-2.98 (1H, m), 3.00-3.16 (1H, m) , 4.72-4.92 (1H, m), 5.05 (1H, d, J = 4.0 Hz) , 6.60-6.80 (1H, m) , 7.02-7.20 (3H, m), 7.22-7.60 (8H, m), 7.62-7.78 (1H, m), 8.05 (1H, d, J = 8.4 Hz), 8.82 (1H, brs).

Reference： [1]Patent: EP1362846,2003,A1 .Location in patent: Page/Page column 61

44
[ 5632-16-6 ]
[ 486-74-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 5532 - 5535

45
[ 486-74-8 ]
[ 603113-12-8 ]
N-(2-((5aS,7S)-3-methyl-1-oxo-1,5a,6,7,8,9-hexahydropyrano[4,3-b]chromen-7-yl)propyl)quinolie-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 25℃; for 12h;Inert atmosphere;	A mixture of 43 mg (0.15 mmol) of amine 10, 42 mg (0.24 mmol) of quinoline-4-carboxylic acid (18), 56 mg (0.36 mmol) of EDC, and 2 mg (0.02 mmol) of DMAP in 5 mL of dichloromethane was stirred under argon at 25oC for 12 h. The reaction mixture was diluted with 100 mL of dichloromethane, washed with water, and brine, dried (MgSO4), concentrated, and column chromatographed on silica gel using a gradient mixture of hexane and ethyl acetate as eluant to give 43 mg (65percent yield) of compound 8, as a solid. 1H NMR delta 8.82 (d, J = 4.3 Hz, 1 H), 8.16 (d, J = 8.6 Hz, 1 H), 8.08 (d, J = 8.6 Hz, 1 H), 7.73 (t, J = 7.6 Hz, 1 H), 7.57 (t, J = 7.6 Hz, 1 H), 7.34 (d, J = 4.3 Hz, 1 H), 6.72 (br. s, 1 H, NH), 5.97 (s, 1 H), 5.68 (s, 1 H), 5.09 - 4.98 (m, 1 H), 3.63 - 3.52 (m, 1 H), 3.42 - 3.29 (m, 1 H), 2.43 (d, J = 13.3 Hz, 1 H), 2.14 (s, 4 H), 2.06 - 1.90 (m, 1 H), 1.87 - 1.71 (m, 2 H), 1.71 - 1.51 (m, 2 H), 1.43 - 1.11 (m, 1 H), 0.99 (d, J = 6.6 Hz, 1.5 H, CH3) 0.98 (d, J = 6.6 Hz, 1.5 H, CH3) (2 diastereomers at C12); 13C NMR delta 167.7, 163.5, 162.7, 161.8, 149.9, 148.7, 142.4, 132.4, 130.2, 129.9, 127.8, 125.4, 124.6, 118.5, 109.4, 99.9, 97.4, 79.6, 79.4, 43.9, 39.2, 38.8, 38.7, 38.0, 36.9, 32.4, 32.3, 31.1, 28.6, 20.2, 14.5, 14.4; MS (electrospray ionization) m/z 453.3 (M + Na+), 431.1 (M+H+); HRMS calcd for C26H27N2O4+ (M+H+) 431.1971, found 431.1957 (100percent).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 3480 - 3484

46
[ 20503-40-6 ]
[ 486-74-8 ]
[ 1430330-71-4 ]

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 28h;Inert atmosphere;	General procedure: To a solution of cyanoacetic acid (340 mg, 4.0 mmol) and 1,1-dioxo-1H-1lambda6-benzo[b]thiophen-6-ylamine (362 mg, 2.0 mmol) in 10 mL of CH2Cl2 was added DIPEA (774 mg, 6.0 mmol). HBTU (1.14 g, 3.0 mmol) was added at 0 °C. The resulting mixture was stirred at r.t. for 28 h. The reaction mixture was diluted with CH2Cl2 (80 mL) and washed with water (20 mL). The organic layer was separated and dried with anhydrous Na2SO4. The solution was concentrated to give a crude product, which was purified with silica gel column (EtOAc/hexane = 1/1) to obtain the desired product (400 mg, 81percent) as a yellow solid (mp 207-208 °C). HPLC purity 98.6percent (tR = 10.93 min). 1H NMR (600 MHz, DMSO-d6) delta 10.79 (s, 1H), 8.04 (s, 1H), 7.67-7.69 (m, 1H), 7.60 (d, 1H, J = 7.2 Hz), 7.57 (d, 1H, J = 7.8 Hz), 7.30 (d, 1H, J = 7.2 Hz), 3.98 (s, 2H). 13C NMR (150 MHz, DMSO-d6) delta 162.0, 140.7, 137.3, 132.8, 130.3, 126.7, 126.1, 123.4, 115.6, 111.4, 27.0. HRMS (ESI) calcd for C11H19N2O3S 249.0328 (M + H)+, found 249.0330.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 62,p. 498 - 507

47
[ 1145966-18-2 ]
[ 486-74-8 ]
[ 1428264-45-2 ]

Yield	Reaction Conditions	Operation in experiment
38%		-A-(2-(2-cyanopyrrolidin-1-yl)-2-oxoethyl)quinoline-4-carboxamide Commercially available quinoline-4-carboxylic acid (0.078g, 0.449 mmol) was dissolved in 7 ml of DMF, A/-ethyl-/V-isopropylpropan-2-amine (0.242ml, 1.347 mmol), HOBT (0.069 g, 0.449 mmol) and TBTU (0.144g, 0.449mmol) were added. After 15 min a solution of (S)-1-(2- aminoacetyl)pyrrolidine-2-carbonitrile 2,2,2-trifluoroacetate (0.120 g, 0.449 mmol) (prepared as described under A.1 of the experimental part) in DMF was added. The mixture was stirred overnight at room temperature. The volatiles were evaporated, the residue was dissolved in ethyl - - acetate and extracted with 1 N citric acid, saturated sodium bicarbonate and brine. The solution was dried over sodium sulfate, filtrated and evaporated. It was purified using column chromatography (1 -5 hexane-ethyl acetate). Yield: 66 mg, 38percent 1 H NMR (400 MHz, CDCI3) : (8.5/1 .5 mixture of trans/cis amide rotamers) delta 2.12 - 2.38 (m, 4H), 3.50 - 3.58 (m, 1 H), 3.68-3.74 (m , 1 H), 4.27 (dd, J= 1 7.6, 4.1 Hz, 0.85H), 4.33 (dd, J= 17.3, 4.3 Hz, 0.15H), 4.43 (dd, J= 18.0, 5.0 Hz, 0.85H), 4.60 (dd, J= 17.3, 5.4 Hz, 0.15H), 4.75 - 4.78 (m, 1 H), 7.14 (br s, 1 H), 7.49 (d, J = 6 Hz, 1 H), 7.62 (d tr, J = 7.7 Hz, J= 1 .3 Hz, 1 H), 7.77 (d tr, J = 7.6, 1 .4 Hz, 1 H), 8.15 (d, J= 8.49 Hz, 1 H), 8.28 (dd, J = 8.07, 0.79 Hz, 1 H) , 8.95 (d, J = 4.3 Hz, 1 H) MS (ESI) m/z 331 .1 [M+Na]+ LC-MS (l-B) Rt 9.7 min, m/z 309.0 [M+H]+ (97percent).
38%		Commercially available quinoline-4-carboxylic acid (0.078 g, 0.449 mmol) was dissolved in 7 ml of DMF, N-ethyl-N-isopropylpropan-2-amine (0.242 ml, 1.347 mmol), HOBT (0.069 g, 0.449 mmol) and TBTU (0.144 g, 0.449 mmol) were added. After 15 min a solution of (S)-1-(2-aminoacetyl)pyrrolidine-2-carbonitrile 2,2,2-trifluoroacetate (0.120 g, 0.449 mmol) (prepared as described under A.1 of the experimental part) in DMF was added. The mixture was stirred overnight at room temperature. The volatiles were evaporated, the residue was dissolved in ethyl acetate and extracted with 1 N citric acid, saturated sodium bicarbonate and brine. The solution was dried over sodium sulfate, filtrated and evaporated. It was purified using column chromatography (1-5 hexane-ethyl acetate). Yield: 66 mg, 38percent 1H NMR (400 MHz, CDCl3): (8.5/1.5 mixture of trans/cis amide rotamers) delta 2.12-2.38 (m, 4H), 3.50-3.58 (m, 1H), 3.68-3.74 (m, 1H), 4.27 (dd, J=17.6, 4.1 Hz, 0.85H), 4.33 (dd, J=17.3, 4.3 Hz, 0.15H), 4.43 (dd, J=18.0, 5.0 Hz, 0.85H), 4.60 (dd, J=17.3, 5.4 Hz, 0.15H), 4.75-4.78 (m, 1H), 7.14 (br s, 1H), 7.49 (d, J=6 Hz, 1H), 7.62 (d tr, J=7.7 Hz, J=1.3 Hz, 1H), 7.77 (d tr, J=7.6, 1.4 Hz, 1H), 8.15 (d, J=8.49 Hz, 1H), 8.28 (dd, J=8.07, 0.79 Hz, 1H), 8.95 (d, J=4.3 Hz, 1H) MS (ESI) m/z 331.1 [M+Na]+ LC-MS (I-B) Rt 9.7 min, m/z 309.0 [M+H]+ (97percent).

Reference： [1]Patent: WO2013/107820,2013,A1 .Location in patent: Page/Page column 48; 49
[2]Patent: US2014/357650,2014,A1 .Location in patent: Paragraph 0327; 0328; 0329; 0330; 0331; 0332

48
[ 1448440-40-1 ]
[ 486-74-8 ]
[ 1448440-52-5 ]

Yield	Reaction Conditions	Operation in experiment
45%		2.2 Synthesis of final products of formula (I), via intermediates (D) and (E), as defined in Scheme 1. -(2-(2-cyano-4,4-difluoropyrrolidin-1-yl)-2-oxoethyl)quinoline-4-carboxamide Commercially available quinoline-4-carboxylic acid (0.065 g, 0.377 mmol) was dissolved in 7 ml of DMF, A/-ethyl-/V-isopropylpropan-2-amine (0.210 ml, 1 .168 mmol), HOBT (0.058 g, 0.377 mmol) and TBTU (0.121 g, 0.377mmol) were added. After 15 min a solution of (S)-1 -(2-aminoacetyl)-4,4- difluoropyrrolidine-2-carbonitrile trifluoroacetate (0.085g, 0.377mmol) (prepared as described under A.2 of the experimental part) in DMF was added. The mixture was stirred overnight at room - - temperature. The volatiles were evaporated, the residue was dissolved in ethyl acetate and washed with 1 N citric acid, saturated sodium bicarbonate and brine. The solution was dried over sodium sulfate, filtrated and evaporated. It was purified using column chromatography (1-4 hexane- ethyl acetate). Yield: 64mg, 45percent 1H NMR (400 MHz, CDCI3): (8.5/1.5 mixture of trans/cis amide rotamers) delta 2.72 - 2.83 (m, 2H), 3.91 -4.07 (m, 2H), 4.21 (dd, J= 17.4, 4.2 Hz, 0.85H), 4.33 (dd, J= 17.4, 4.3 Hz, 0.15H), 4.39 (dd, J= 17.4, 5.6 Hz, 0.85H), 4.70 (dd, J= 17.4, 5.7 Hz, 0.15H), 4.92-4.99 (m, 0.85H), 5.15 (d, J = 9 Hz, 0.15H), 7.30 (s, 1 H), 7.49 (dd, J= 10.11 , 4.30 Hz, 1 H), 7.60 (dd, J = 11.22, 4.11 Hz, 1 H), 7.74 (t, J= 7.69 Hz, 1H), 8.12 (d, J= 8.42 Hz, 1H), 8.23 (t, J= 9.99 Hz, 1H), 8.96 - 8.86 (m, 1H). MS (ESI) m/z 345.0 [M+1]+ LC-MS (l-B) Rt10.8 min, m/z 345.0 [M+H]+ (98percent).
45%		Commercially available quinoline-4-carboxylic acid (0.065 g, 0.377 mmol) was dissolved in 7 ml of DMF, N-ethyl-N-isopropylpropan-2-amine (0.210 ml, 1.168 mmol), HOBT (0.058 g, 0.377 mmol) and TBTU (0.121 g, 0.377 mmol) were added. After 15 min a solution of (S)-1-(2-aminoacetyl)-4,4-difluoropyrrolidine-2-carbonitrile trifluoroacetate (0.085 g, 0.377 mmol) (prepared as described under A.2 of the experimental part) in DMF was added. The mixture was stirred overnight at room temperature. The volatiles were evaporated, the residue was dissolved in ethyl acetate and washed with 1 N citric acid, saturated sodium bicarbonate and brine. The solution was dried over sodium sulfate, filtrated and evaporated. It was purified using column chromatography (1-4 hexane-ethyl acetate). Yield: 64 mg, 45percent 1H NMR (400 MHz, CDCl3): (8.5/1.5 mixture of trans/cis amide rotamers) delta 2.72-2.83 (m, 2H), 3.91-4.07 (m, 2H), 4.21 (dd, J=17.4, 4.2 Hz, 0.85H), 4.33 (dd, J=17.4, 4.3 Hz, 0.15H), 4.39 (dd, J=17.4, 5.6 Hz, 0.85H), 4.70 (dd, J=17.4, 5.7 Hz, 0.15H), 4.92-4.99 (m, 0.85H), 5.15 (d, J=9 Hz, 0.15H), 7.30 (s, 1H), 7.49 (dd, J=10.11, 4.30 Hz, 1H), 7.60 (dd, J=11.22, 4.11 Hz, 1H), 7.74 (t, J=7.69 Hz, 1H), 8.12 (d, J=8.42 Hz, 1H), 8.23 (t, J=9.99 Hz, 1H), 8.96-8.86 (m, 1H). MS (ESI) m/z 345.0 [M+1]+ LC-MS (I-B) Rt 10.8 min, m/z 345.0 [M+H]+ (98percent).

Reference： [1]Patent: WO2013/107820,2013,A1 .Location in patent: Page/Page column 47; 48
[2]Patent: US2014/357650,2014,A1 .Location in patent: Paragraph 0317; 0318; 0319; 0320; 0321

49
C₁₇H₂₇N₄O₃⁽¹⁺⁾*I^(1-) [ No CAS ]
[ 486-74-8 ]
C₂₂H₂₇N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
177 mg	With triethylamine; In acetonitrile; at 20℃; for 72h;	General procedure: Methyl iodide (570 mg, 4 mmol) was added to a stirred solution of 14 (320 mg, 1 mmol) dissolved in dry MeCN (2 mL) and dry THF (2 mL) at rt. The volatiles were removed under reduced pressure after 24 h, the residue was dissolved in dry MeCN (4 mL), and Et3N (101 mg, 1 mmol) and the appropriate carboxylic acid (1 mmol) were added. The solution was allowed to stir at rt for 12?120 h before the volatiles were removed under reduced pressure. The residue was purified by flash chromatography (silica gel, mixtures of CH2Cl2 and MeOH?40:1, 20:1 or 9:1).

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 7283 - 7308

50
[ 1416238-73-7 ]
[ 486-74-8 ]
[ 1416235-03-4 ]

Yield	Reaction Conditions	Operation in experiment
15%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;	<strong>[486-74-8]Quinoline-4-carboxylic acid</strong> (361 mg, 1.74 mmol) was dissolved in methylene chloride (10 ml), and mixed with EDCI (397 mg, 2.08 mmol) and HOBt (281 mg, 2.08 mmol) for min and then with 9b-amino-6-ethyl-4b-hydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one (500 mg, 1.74 mmol) overnight at room temperature while stirring. After extraction with CH2Cl2 and water, the organic layer was dried over MgSO4 and concentrated in a vacuum. Purification by column chromatography (EA:Hex=1:1) afforded the title compound as a white solid. 112 mg (15percent). [0982] 1H-NMR (500 MHz, CDCl3) delta 6.86 (d, J=8.6 Hz, 1H ArH), 7.19 (s, 1H, NH), 7.277.29 (m, 1H, ArH), 7.43 (d, J=2.1 Hz, 1H, ArH), 7.53 (d, J=4.2 Hz, 1H, ArH), 7.60-7.65 (m, 2H, ArH), 7.78 (t, J=7.9 Hz, 1H, ArH), 7.87-7.91 (m, 2H, ArH), 8.06-8.11 (m, 2H, ArH), 8.16 (d, J=8.1 Hz, 1H, ArH), 8.98 (d, J=4.2 Hz, 1H, ArH).

Reference： [1]Patent: US2014/114068,2014,A1 .Location in patent: Paragraph 0981-0982

51
[ 486-74-8 ]
4-amino-3-hydroxynaphthalene-2,7-disulfonic acid disodium salt [ No CAS ]
2-quinolin-4-ylnaphtho[1,2-d]oxazole-4,7-disulfonic acid disodium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15%	With trimethylsilyl polyphosphate; In 1,2-dichloro-benzene; at 180℃; for 9h;	Precursor: 2-Quinolin-4-ylnaphtho[1,2-d]oxazole-4,7-disulfonic acid disodium salt 1 g of 4-amino-3-hydroxynaphthalene-2,7-disulfonic acid disodium salt, 480 mg of quinoline-4-carboxylic acid and 4.0 g of trimethylsilyl polyphosphate are heated in 6 ml of 1,2-dichlorobenzene to 180 C. for 9 hours. Cooling is followed by suspending with 20 ml of dichloromethane and neutralizing by admixture of 40 ml of 1N NaOH solution. The aqueous phase is separated off and purified via RP chromatography. Yield: 205 mg (15%) (C20H10N2O7S2Na2, 500.42 g/mol) MS ESI-(m/z): 227 (base, [M]2-)

Reference： [1]Patent: US2015/175591,2015,A1 .Location in patent: Paragraph 0290; 0291; 0292; 0293

52
[ 5959-58-0 ]
[ 486-74-8 ]
2-quinolin-4-yl-naphtho[1,2-d]oxazole-5-sulfonic acid sodium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10%	With trimethylsilyl polyphosphate; In 1,2-dichloro-benzene; at 180℃; for 12h;	Precursor: 2-Quinolin-4-yl-naphtho[1,2-d]oxazole-5-sulfonic acid sodium salt 700 mg of 1-amino-2-naphthol-4-sulfonic acid sodium salt, 500 mg of quinoline-4-carboxylic acid and 2 g of trimethylsilyl polyphosphate are heated in 7 ml of 1,2-dichlorobenzene to 180 C. for 12 hours. Cooling is followed by suspending with 20 ml of dichloromethane and neutralizing by admixture of 20 ml of 1N NaOH solution. This is followed by treatment in an ultrasonication bath until the tacky precipitate has substantially dissolved. The aqueous phase is separated off and purified via RP chromatography. [0184] Yield: 115 mg (10%) (C20H11N2O4SNa, 398.38 g/mol) [0185] MS ESI-(m/z): 375 (base, [M]-)

Reference： [1]Patent: US2015/175591,2015,A1 .Location in patent: Paragraph 0182; 0183; 0184; 0185

53
4-aminoresorcinol hydrochloride [ No CAS ]
[ 486-74-8 ]
2-quinolin-4-ylbenzooxazol-6-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With N-ethyl-N,N-diisopropylamine; In 1,2-dichloro-benzene; at 180℃; for 6h;	Precursor 1: 2-Quinolin-4-ylbenzooxazol-6-ol 0.933 g of 4-aminoresorcinol hydrochloride, 1.0 g of 4-quinolinecarboxylic acid and 4 g of trimethylsilyl polyphosphate are heated in 10 ml of 1,2-dichlorobenzene and 0.99 ml of ethyldiisopropylamine to 180 C. for 6 hours. Cooling is followed by suspending with 70 ml of dichloromethane and neutralizing by admixture of 40 ml of 1N NaOH solution. This is followed by treatment in an ultrasonication bath until there is a pale gray fine precipitate, which is filtered, washed with a little water and a little dichloromethane and dried. Yield: 595 mg (39%) (C16H10N2O2, 262.27 g/mol) MS ESI-(m/z): 261 (base, [M-H]-)

Reference： [1]Patent: US2015/175591,2015,A1 .Location in patent: Paragraph 0153; 0154; 0155; 0156

54
[ 486-74-8 ]
[ 71294-66-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sulfuric acid; sulfur trioxide / 2 h / 200 °C / Sealed tube 2.1: potassium hydroxide / water 2.2: 300 °C 3.1: thionyl chloride / 2 h / 0 - 20 °C / Inert atmosphere

Reference： [1]Thinnes; Tumber; Yapp; Scozzafava; Yeh; Chan; Tran; Hsu; Tarhonskaya; Walport; Wilkins; Martinez; Müller; Pugh; Ratcliffe; Brennan; Kawamura; Schofield [Chemical Communications, 2015, vol. 51, # 84, p. 15458 - 15461]

55
5-methyl-7-(piperidin-3-yl)-[1,2,4]triazolo[1,5-a]pyrimidine [ No CAS ]
[ 486-74-8 ]
[ 76-05-1 ]
(3-(5-methyl-[1,2,4]triazolo[1 ,5-a]pyrimidin-7-yl)piperidin-1-yl)(quinolin-4-yl)methanone trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29%		Example 7. (3 -(5 -Methyl- Gamma 1 ,2,41triazolor 1 ,5-a1pyrimidin-7-yl)piperidin- 1 - yl)(quinolin-4-yl)methanone To a 1 dram screw cap vial was added quinoline-4-carboxylic acid (0.1 1 mmol), HATU (0.2 mL of a 0.55 M solution in DMF, 0.1 1 mmol) and DIPEA (20 mu, 0.1 1 mmol). The mixture was stirred at rt for 30 min then 5-methyl-7-(piperidin-3-yl)-[ l ,2,4]triazolo[l ,5- a]pyrimidine (0.109 mmol, 0.6 mL of a 0.1817 M solution in DIPEA and DMF) was added. The vial was sealed and shaken at rt overnight. The mixture was filtered, a 5mu aliquot taken and diluted with 200 DMF and an analytical reverse-phase-UPLC was taken. The desired product mass was observed. Subsequently, based on the retention time of the desired product from the analytical UPLC, a corresponding PREP-HPLC gradient was recommended and the compound was purified. Obtained was the title compound (15 mg, 29percent) as the TFA salt. [M+H] = 373.2.

Reference： [1]Patent: WO2015/164508,2015,A1 .Location in patent: Page/Page column 59

56
(2-[5-(trifluoromethyl)-2-pyridyl]sulfonyl}ethyl)amine hydrochloride [ No CAS ]
[ 486-74-8 ]
N-(2-((5-(trifluoromethyl)pyridin-2-yl)sulfonyl)ethyl)quinoline-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%		General procedure: To a suspension of the acid(0.25 mmol, 1.00 equiv) and N,N,N0 ,N0-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (HBTU) (0.25 mmol,1.00 equiv) in CH2Cl2 (2.5 mL), under an air atmosphere, at ambienttemperature, was added diisopropylethylamine (0.1 mL,0.58 mmol, 2.34 equiv) and the mixture was stirred for 25 min.2-((5-(Trifluoromethyl)pyridin-2-yl)sulfonyl)ethan-1-aminiumchloride(14) (0.26 mmol, 1.05 equiv) and CH2Cl2 (5 mL) were thenadded and the mixture was stirred for 48 h. The reaction wasquenched with aqueous HCl (1 M, 2 mL), followed by H2O(10 mL) and EtOAc (20 mL). The mixture was transferred to a separatoryfunnel and the flask rinsed with EtOAc (10 mL). The organicphase was separated, washed with saturated aqueous NaHCO3(15 mL) and dried over anhydrous Na2SO4. The solvent was thenremoved under reduced pressure, at or below 40 C, to afford thecrude product. Purification was performed as indicated for eachcompound below 5.3.6.15 N-(2-((5-(Trifluoromethyl)pyridin-2-yl)sulfonyl)ethyl)quinoline-4-carboxamide (45) The title compound was prepared from quinoline-4-carboxylic acid (97percent, 0.045 g, 0.25 mmol). The crude product was purified by flash chromatography on silica gel (0:100-2:98/CH3OH:CH2Cl2) affording a colourless solid (0.075 g, 0.18 mmol, 73percent). 1H NMR (600 MHz, DMSO-d6) delta 9.21 (m, 1H), 8.94 (d, J = 4.3 Hz, 1H), 8.91 (t, J = 5.6 Hz, 1H), 8.58 (dd, J = 8.2, 2.2 Hz, 1H), 8.31 (d, J = 8.2 Hz, 1H), 8.16 (br dd, J = 8.4, 1.3 Hz, 1H), 8.06 (br d, J = 8.3 Hz, 1H), 7.81 (ddd, J = 8.4, 6.8, 1.4 Hz, 1H), 7.66 (ddd, J = 8.3, 6.9, 1.3 Hz, 1H), 7.38 (d, J = 4.3 Hz, 1H), 3.93 (t, J = 6.5 Hz, 2H), 3.75 (q, J = 6.2 Hz, 2H). 13C NMR13C NMR (151 MHz, DMSO-d6) delta 166.6, 159.9 (q, J = 1.4 Hz), 150.0, 147.9, 147.4 (q, J = 3.9 Hz), 141.0, 137.1 (q, J = 3.5 Hz), 129.8, 129.3, 128.5 (q, J = 33.0 Hz), 127.3, 125.5, 123.9, 122.7 (q, J = 273.3 Hz), 122.4, 119.0, 50.4, 33.4. HRMS (ESI) Calcd for C18H14F3N3NaO3S [M+Na]+: 432.0600; found 432.0607 (-1.6 ppm). HPLC (CH3OH:H2O/50:50, 1 mL/min, 254 nm) tr(major) 11.68 min (>99percent).

Reference： [1]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 247 - 260

57
[ 114878-60-3 ]
[ 486-74-8 ]
(4-(2-chloro-4-nitro-phenyl)piperazine-1-yl)(quinolin-4-yl)-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 12h;	<strong>[486-74-8]Quinoline-4-carboxylic acid</strong> (72 mg, 0.41 mmol)and 1-(2-chloro-4-nitrophenyl)piperazine (72 mg, 0.41 mmol) in dimethylformamide (2 mL) It is dissolved in triethylamine (0.14 mL, 1.03 mmol) to the reaction mixture dry high-profile and (propylphosphonic anhydride, 0.37 mL, 0.62 mmol) It was added and Stirring for 12 hours the reaction mixture at room temperature, concentrating it under reduced pressure extracted. And then being washed with brine saturation of at said extract, the drying in the form of tetrabutylammonium sodium. Dried reaction mixture solids of a dark brown comes concentrated under the reduced pressure obtained. Said obtained mixture column chromatography (ethyl acetate/n = 2:3-hexanediol) for purifying the yellow solid thereby, a desired compound (120 mg, 75percent) is obtained.
75%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; for 12h;	<strong>[486-74-8]Quinoline-4-carboxylic acid</strong>(72 mg,0.41mmol) and 1-(2-chloro-4-nitro phenyl)piperazine( 72 mg , 0.41 mmol ), the dimethiconeDissolved in butyl formamide (2 mL). The reaction mixture triethylamine ( 0.14 mL , 1.03 mmol ) was added ( propylphosphonic anhydride , 0.37 mL , 0.62 mmol ) . the reaction mixture was stirred for 12 hours and then concentrated under reduced pressure and was extracted twice with ethyl acetate. The extract saturated salt Washed , dried with sodium sulfate and water. The dried reaction mixture was concentrated under reduced pressure to give a dark brown solid .The mixture thus obtained was purified by column chromatography ( ethyl acetate / n- hexane = 2 : 3) to obtain the target compound as a yellow solid ( 120 mg , 75 percent ).
75%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 12h;	quinoline-4-carboxylic acid (72 mg, 0.41 mmol) and 1 - (2-chloro-4-nitro-phenyl) piperazine (72 mg, 0.41 mmol) to dimethylformamide (2 mL) to dissolve thereby. The reaction mixture triethylamine (0.14 mL, 1.03 mmol) was added to the profile, and a high dry-c phosphonic sulphonic not de (propylphosphonic anhydride, 0.37 mL, 0.62 mmol). Stirring for 12 hours the reaction mixture at room temperature, and concentrated under reduced pressure and extracted two times with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate. The dried reaction mixture was concentrated under reduced pressure to give a dark brown solid thus obtained and the mixture was purified by column chromatography (ethyl acetate / n- hexane = 2: 3) to give the target compound as a yellow solid (120 mg, 75percent) a obtained.

Reference： [1]Patent: KR2016/21163,2016,A .Location in patent: Paragraph 0514-0517
[2]Patent: KR2015/134301,2015,A .Location in patent: Paragraph 0514; 0515; 0516
[3]Patent: KR2015/25531,2015,A .Location in patent: Paragraph 0514; 0515; 0516

58
[ 1005-38-5 ]
[ 486-74-8 ]
N-(6-chloro-2-(methylthio)pyrimidine-4-one)quinoline-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
11%	With pyridine; trichlorophosphate; at 80℃; for 1h;	Quinoline-4-carboxylic acid (36.4 mg, 0.226 mmol),3-chloro-5-(methylthio)benzene amine (50.0 mg, 0.205 mmol)and POCl3 (34.6 mg, 0.226 mmol)Dissolved in pyridine (1 mL)and stirred at 80°C for 1 hour. Thin film chromatography (TLC) in verifying, new spot the system is moved, and adding water to the composition, a reaction mixture of a, die chloro methane at extracted times 2. The organic layer extracted are dried, using magnesium sulfate, after, concentrating it under reduced pressure, organic for extract of moisture MgSO4removal of filtering the concentrate and a thin silica gel fraction is concentrated to after chromatography (preparative TLC, n/ethyl acetate = 1/1-hexanediol) for purifying the white solid thereby, a desired compound (11percent) is obtained.
11%	With pyridine; trichlorophosphate; at 80℃; for 1h;	quinoline-4-carboxylic acid ( 36.4 mg , 0.226 mmol ) ,6-chloro-2-(methylsulfanyl)pyrimidin-4-amine( 50.0 mg , 0.205 mmol ) and POCl3 ( 34.6 mg , 0.226 mmol ) in pyridine (1 mL) and stirred at 80°C for 1 hour. When the thin film check chromatography (TLC), when a new spot is confirmed , water was added to the reaction mixture twice with dichloromethane It was extracted . The extracted organic layer was dried using magnesium sulfate, and then concentrated under reduced pressure , the water content of the organic extractAfter removing MgSO4 by filtration and then concentrated by preparative silica gel thin layer chromatography ( preparative TLC , ethyl acetate/ N- hexane = 1/ 1) to obtain the title compound ( 11percent) as a white solid
11%	With pyridine; trichlorophosphate; at 80℃; for 1h;	Quinoline-4-carboxylic acid (36.4 mg, 0.226 mmol),3-chloro-5 - (methylthio) benzene amine (50.0 mg, 0.205 mmol) and POCl3 (34.6 mg, 0.226 mmol), pyridine (1 mL) was dissolved in, 80 was stirred for 1 hour dongan. When thin layer chromatography (TLC) check when, a new spot is confirmed, water was added to the reaction mixture, and extracted twice with dichloromethane. And the extracted organic layer was dried using magnesium sulfate, vacuum concentrated and, after the water was removed by filtration of the organic extract over MgSO4 and concentrated by silica gel preparative thin layer chromatography (preparative TLC, ethyl acetate / n- hexane = l / l ) to give to give the title compound (11percent) of a white solid.

Reference： [1]Patent: KR2016/21163,2016,A .Location in patent: Paragraph 0729-0732
[2]Patent: KR2015/134301,2015,A .Location in patent: Paragraph 0729; 0730; 0731
[3]Patent: KR2015/25531,2015,A .Location in patent: Paragraph 0729; 0730; 0731

59
[ 1005-38-5 ]
[ 486-74-8 ]
N-(6-(3-aminophenyl)-2-(methylthio)pyrimidine-4-one)quinoline-4-carboxamide [ No CAS ]

Reference： [1]Patent: KR2016/21163,2016,A
[2]Patent: KR2015/25531,2015,A

60
[ 486-74-8 ]
[ 77766-06-4 ]
N-(2-(methylthio)-6-phenylpyrimidine-4-one)-N-(quinoline-4-carbonyl)quinoline-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 12h;	quinoline-4-carboxylic acid (72 mg, 0.41 mmol) and 1 - (2-chloro-4-nitro-phenyl) piperazine (72 mg, 0.41 mmol) to dimethylformamide (2 mL) to dissolve thereby. The reaction mixture triethylamine (0.14 mL, 1.03 mmol) was added to the profile, and a high dry-c phosphonic sulphonic not de (propylphosphonic anhydride, 0.37 mL, 0.62 mmol). Stirring for 12 hours the reaction mixture at room temperature, and concentrated under reduced pressure and extracted two times with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate. The dried reaction mixture was concentrated under reduced pressure to give a dark brown solid thus obtained and the mixture was purified by column chromatography (ethyl acetate / n- hexane = 2: 3) to give the target compound as a yellow solid (120 mg, 75percent) a obtained. Instead of using one equivalent of quinolin-4-carboxylic acid in Example 29, using quinoline-4-carboxylic acid, and using 2 equivalents of 1- (2-chloro-4-nitro phenyl) piperazine but using 2- (methylthio) -6-phenyl-pyrimidin-4-amine in place of and performs in the same manner as in example 29 to give the title compound (30percent).

Reference： [1]Patent: KR2015/25531,2015,A .Location in patent: Paragraph 0516;0624; 0625; 0626

61
[ 3435-29-8 ]
[ 486-74-8 ]
N-(6-phenylpyrimidine-4-one)-N-(quinoline-4-carbonyl)quinoline-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
11%	With pyridine; trichlorophosphate; at 80℃; for 1h;	Quinoline-4-carboxylic acid (36.4 mg, 0.226 mmol),3-chloro-5 - (methylthio) benzene amine (50.0 mg, 0.205 mmol) and POCl3 (34.6 mg, 0.226 mmol), pyridine (1 mL) was dissolved in, 80 was stirred for 1 hour dongan. When thin layer chromatography (TLC) check when, a new spot is confirmed, water was added to the reaction mixture, and extracted twice with dichloromethane. And the extracted organic layer was dried using magnesium sulfate, vacuum concentrated and, after the water was removed by filtration of the organic extract over MgSO4 and concentrated by silica gel preparative thin layer chromatography (preparative TLC, ethyl acetate / n- hexane = l / l ) to give to give the title compound (11%) of a white solid.

Reference： [1]Patent: KR2015/25531,2015,A .Location in patent: Paragraph 0729; 0730; 0731

62
[ 6638-79-5 ]
[ 486-74-8 ]
[ 864674-12-4 ]

Yield	Reaction Conditions	Operation in experiment
		To a stirred solution of quinoline-4-carboxylic acid (12.00 g, 69.30 mmol) in anhydrous dichloromethane (50 ml) was added 2-(3H-[l,2,3]triazolo[4,5-b]pyridin-3-yl)- 1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (39.52 g, 103.95 mmol). The mixture solution was stirred for 15 minutes at room temperature (15 °C), and then N-ethyl-N- isopropylpropan-2-amine (26.87 g, 207.89 mmol) and Nu,Omicron-dimethylhydroxylamine hydrochloride (8.1 g, 83.16 mmol) were slowly added to the reaction solution. The reaction solution was stirred for 12 hr at room temperature. The reaction solution was quenched by addition of water (50 ml) and concentrated. The aqueous solution was extracted with ethyl acetate (50 mL x 3). The combined organics layer was dried over sodium sulfate, filtered and concentrated to afford the crude N-methoxy-N-methylquinoline-4-carboxamide (14.98 g). It was used in next step directly.

Reference： [1]Patent: WO2016/130396,2016,A1 .Location in patent: Paragraph 0079; 0080; 0081

63
[ 625-98-9 ]
[ 486-74-8 ]
3-(3-fluorophenyl)quinoline-4-carboxylic acid [ No CAS ]

Reference： [1]Organic Letters,2016,vol. 18,p. 6094 - 6097

64
[ 4381-25-3 ]
[ 486-74-8 ]
N-[quinoline-4-carboxyl]-S-methyl-S-phenylsulfoximine [ No CAS ]

Reference： [1]Organic Letters,2016,vol. 18,p. 6416 - 6419

65
(4-bromophenyl)((2S)-2-(4-chlorophenyl)piperazin-1-yl)methanone hydrochloride [ No CAS ]
[ 486-74-8 ]
((3S)-4-(4-bromobenzoyl)-3-(4-chlorophenyl)piperazin-1-yl)(quinolin-4-yl)methanone [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2017,vol. 8,p. 1077 - 1082

66
[ 486-74-8 ]
C₁₀H₅NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%		Under nitrogen protection conditions,17.3 g (100 mmol) of quinoline-4-carboxylic acid was dissolved in 100 mL of tetrahydrofuran.Mix with 157 mL (220 mmoL) sec-butyl lithium (1.4 M) at -40 ° C to remove the freezer.The reaction solution was allowed to stand in the water bath at room temperature for 60 minutes.Stir for 2 hours, cool at -78 ° C,100 mL of tetrahydrofuran mixed with 14.4 g (150 mmol) of methanesulfonic acid was added dropwise.Remove the cold sink,The mixture was allowed to stand at room temperature for 30 minutes in a water bath, and refluxed at 60 ° C for 5 hours.After the reaction was stopped, it was washed with saturated sodium chloride and then 2N aqueous HCl solution and stirred for 30 min. The water in the organic layer was removed with anhydrous magnesium sulfate, and the mixture was filtered with suction.Intermediate TM-1 6.2 g (40percent) was obtained.

Reference： [1]Patent: CN109053810,2018,A .Location in patent: Paragraph 0022; 0023; 0024; 0025; 0026

67
[ 486-74-8 ]
[ 6281-32-9 ]

Yield	Reaction Conditions	Operation in experiment
54.39%	With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃; for 3h;	To a stirred solution of quinoline-4-carboxylic acid (1 g, 5.77 mmol, 1 equiv.) in THF (15 mL) was added LiAlH4(0.3 g, 8.66 mmol, 1.5 equiv). The resulting mixture was stirred for 3 h at 0 degrees Celsius. The resulting mixture was concentrated under reduced pressure. This resulted in quinolin-4-ylmethanol(500 mg, 54.39%) as a yellow solid

Reference： [1]Patent: WO2019/55966,2019,A2 .Location in patent: Page/Page column 277

68
[ 486-74-8 ]
[ 1117-97-1 ]
[ 864674-12-4 ]

Yield	Reaction Conditions	Operation in experiment
2.8 g		After adding quinoline-4-carboxylic acid (2.2 g, 12.8 mmol), HATU (5.8 g, 15.3 mmol) and DIPEA (6.7 mL, 38.4 mmol) to dichloromethane (25 mL), the result was stirred for 30 minutes. To the reaction solution, an N,O-dimethylhydroxylamine salt (1.9 g, 19.2 mmol) was introduced, and the result was stirred for 12 hours at room temperature. After terminating the reaction, the reaction solution was removed, and ethyl acetate was added thereto. The result was washed with water and saline, then dried using anhydrous magnesium sulfate, and filtered. The filtrate was concentrated and purified using column chromatography to obtain a target compound (2.8 g). 1H NMR spectrum (300 MHz, CDCl3) delta 8.96(d, 1H), 8.15(d, 1H), 7.86(d, 1H), 7.76(t, 1H), 7.59(t, 1H), 7.39(d, 1H), 3.48-3.40(m, 6H).

Reference： [1]Patent: EP3480193,2019,A1 .Location in patent: Paragraph 0060; 0061

69
C₁₆H₂₅F₂N₃OS*2ClH [ No CAS ]
[ 486-74-8 ]
C₂₆H₃₀F₂N₄O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27 mg	With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 20℃; for 0.333333h;	To the crude compound 11 (30 mg, 0.072 mmol) were added dichloromethane (1.5 mL), quinoline-4-carboxylic acid (14.9 mg, 0.086 mmol), HATU (32.7 mg, 0.086 mmol), triethylamine (0.060 mL, 0.430 mmol). The mixture was stirred at room temperature for 20 minutes. To the reaction mixture was added saturated aqueous solution of sodium hydrogen carbonate. The mixture was extracted with ethyl acetate. The organic layer was washed by saturated aqueous solution of sodium hydrogen carbonate, water, brine, and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform-methanol) to give a compound I-053 (27 mg, yield 75percent).1H-NMR (CDCl3) delta: 1.14-1.41 (m, 5H), 1.51-1.56 (m, 2H), 1.87-1.91 (m, 2H), 2.18-2.22 (m, 2H), 2.56-2.60 (m, 2H), 2.71-2.80 (m, 4H), 3.47 (s, 2H), 4.01-4.13 (m, 1H), 4.54 (td, J=13.1, 4.1 Hz, 2H), 5.83 (d, J=8.2 Hz, 1H), 6.12 (tt, J=55.1, 4.1 Hz, 1H), 7.43 (d, J=4.3 Hz, 1H), 7.62 (t, J=7.7 Hz, 1H), 7.77 (t, J=7.7 Hz, 1H), 8.14 (d, J=8.5 Hz, 1H), 8.21 (d, J=8.5 Hz, 1H), 8.94 (d, J=4.3 Hz, 1H).

Reference： [1]Patent: US2019/161501,2019,A1 .Location in patent: Paragraph 0782; 0789; 0790; 0791

70
(S)-1-(2-aminoacetyl)-4,4-difluoro-N-(4-nitrophenyl)pyrrolidine-2-carboxamide 2,2,2-trifluoroacetate [ No CAS ]
[ 486-74-8 ]
(S)-N-(2-(4,4-difluoro-2-((4-nitrophenyl)carbamoyl)pyrrolidin-1-yl)-2-oxoethyl)quinoline-4-carboxamide [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2019,vol. 10,p. 1173 - 1179

71
[ 6456-74-2 ]
[ 486-74-8 ]
tert-butyl 2-(quinoline-4-carboxamido)acetate [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2019,vol. 10,p. 1173 - 1179

72
(E)-2-hydroxy-1-(methyl(oxo)(phenyl)-λ⁶-sulfaneylidene)guanidine [ No CAS ]
[ 486-74-8 ]
methyl(phenyl)((5-(quinolin-4-yl)-1,2,4-oxadiazol-3-yl)imino)-λ⁶-sulfanone [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 9187 - 9199

73
C₁₆H₂₅F₂N₃OS*ClH [ No CAS ]
[ 486-74-8 ]
C₂₆H₃₀F₂N₄O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 20℃; for 0.333333h;	To compound 11 (30 mg, 0.072 mmol) of the crude product, methylene chloride (1.5 mL), quinoline-4-carboxylic acid (14.9 mg, 0.086 mmol), HATU (32.7 mg, 0.086 mmol), and triethylamine (0.060 mL, 0.430 mmol) and stirred at room temperature for 20 minutes. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium bicarbonate solution, water, and saturated brine, and then dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform-methanol) to obtain compound I-053 (27 mg, yield 75%).

Reference： [1]Patent: TW2019/32461,2019,A .Location in patent: Paragraph 0040; 0041

74
[ 486-74-8 ]
[ 108-95-2 ]
phenyl quinoline-4-carboxylate [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2020,vol. 142,p. 7386 - 7392

Same Skeleton Products

Related Products

Historical Records

Related Functional Groups of
[ 486-74-8 ]

Carboxylic Acids

[ 1078-30-4 ]

7-Quinolinecarboxylic acid

Similarity: 0.92

[ 816448-09-6 ]

8-Methylquinoline-4-carboxylic acid

Similarity: 0.87

[ 1092287-30-3 ]

2-Chloroquinoline-5-carboxylic acid

Similarity: 0.86

[ 31009-04-8 ]

7-Bromoquinoline-4-carboxylic acid

Similarity: 0.86

[ 55240-51-2 ]

2-Phenylisonicotinic acid

Similarity: 0.85

Related Parent Nucleus of
[ 486-74-8 ]

Quinolines

[ 1078-30-4 ]

7-Quinolinecarboxylic acid

Similarity: 0.92

[ 10447-29-7 ]

Ethyl quinoline-4-carboxylate

Similarity: 0.90

[ 816448-09-6 ]

8-Methylquinoline-4-carboxylic acid

Similarity: 0.87

[ 1092287-30-3 ]

2-Chloroquinoline-5-carboxylic acid

Similarity: 0.86

[ 31009-04-8 ]

7-Bromoquinoline-4-carboxylic acid

Similarity: 0.86

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 486-74-8 ] {[proInfo.proName]}

Quality Control of [ 486-74-8 ]

Related Doc. of [ 486-74-8 ]

Product Details of [ 486-74-8 ]

Calculated chemistry of [ 486-74-8 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 486-74-8 ]

Application In Synthesis of [ 486-74-8 ]

[ 486-74-8 ] Synthesis Path-Upstream 1~5

[ 486-74-8 ] Synthesis Path-Downstream 1~74

Related Functional Groups of [ 486-74-8 ]

Carboxylic Acids

Related Parent Nucleus of [ 486-74-8 ]

Quinolines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 486-74-8 ]

Related Parent Nucleus of
[ 486-74-8 ]