[ CAS No. 1810-72-6 ] {[proInfo.proName]}

Name: 1810-72-6|2,6-Dichloroquinoline|97%
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Quality Control of [ 1810-72-6 ]

COA NMR CNMR HPLC LC-MS

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Product Details of [ 1810-72-6 ]

CAS No. :	1810-72-6	MDL No. :	MFCD03427194
Formula :	C₉H₅Cl₂N	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	LPDFGLZUUCLXGM-UHFFFAOYSA-N
M.W :	198.05	Pubchem ID :	607502
Synonyms :

Calculated chemistry of [ 1810-72-6 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	51.76
TPSA :	12.89 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) :	-5.14 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.33
Log Po/w (XLOGP3) :	3.34
Log Po/w (WLOGP) :	3.54
Log Po/w (MLOGP) :	2.98
Log Po/w (SILICOS-IT) :	3.72
Consensus Log Po/w :	3.18

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-3.79
Solubility :	0.0322 mg/ml ; 0.000163 mol/l
Class :	Soluble
Log S (Ali) :	-3.29
Solubility :	0.102 mg/ml ; 0.000515 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.94
Solubility :	0.00229 mg/ml ; 0.0000116 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.38

Safety of [ 1810-72-6 ]

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

Application In Synthesis of [ 1810-72-6 ]

* 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 [ 1810-72-6 ]
Downstream synthetic route of [ 1810-72-6 ]

[ 1810-72-6 ] Synthesis Path-Upstream 1~14

1
[ 6563-10-6 ]
[ 1810-72-6 ]

Yield	Reaction Conditions	Operation in experiment
71%	With trichlorophosphate In dichloromethane; N,N-dimethyl-formamide at 0 - 25℃; Inert atmosphere	General procedure: To a stirred solution of the appropriate azine N-oxides in anhydrous CH₂Cl₂ (0.1M) at 0 °C is added POCl₃ (1.2 equiv) followed by dropwise addition of DMF (0.5 equiv) under argon. The resulting reaction mixture was warmed to 25 °C and stirred for several hours until the reaction is complete as indicated by TLC. Saturated aqueous sodium carbonate solution is added to the reaction mixture slowly to adjust the pH to 7~8. The resulting mixture is separated and the aqueous phase is extracted with CH₂Cl₂ thoroughly. The organic phase is combined and washed with brine, dried over Na₂SO₄, filtered and concentrated under reduced pressure to afford the crude product, which is purified by flash column chromatography using PE/EA (80:1) as eluent.

Reference： [1] European Journal of Organic Chemistry, 2016, vol. 2016, # 8, p. 1606 - 1611
[2] Tetrahedron Letters, 2014, vol. 55, # 51, p. 7130 - 7132

2
[ 1810-67-9 ]
[ 1810-72-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	for 3 h; Reflux	Synthesis of 2,6-dichloro quinoline: 180 mg 6-chloro-2-hydroxy quinoline was treated by 3 ml POCl₃, the mixture was refluxed for 3 hours, the remaining POCl₃was evaporated out. After cooling to room temperature, the residue was treated by cold water, the solid was filtered out and dried as green powder, yield: 90percent. Following the general procedure in claim 5, the listed compounds were achieved. Mass calculated for C₉H₅Cl₂N: 198; LCMS: 200.1 (M+2)⁺; ¹HNMR (400 MHZ), DMSO-d₆) δ ppm 8.04 (1H, d, J=7.8 Hz), 7.97 (1H, d, J=8.8 Hz), 7.81 (1H, d, J=1.9 Hz), 7.68 (1H, dd, J=9.8 Hz, J=2.9 Hz), 7.42 (1H, d, J=8.8 Hz).

Reference： [1] Patent: US2011/190343, 2011, A1, . Location in patent: Page/Page column 27
[2] Journal of Medicinal Chemistry, 2011, vol. 54, # 20, p. 7220 - 7231
[3] Journal of Medicinal Chemistry, 2002, vol. 45, # 14, p. 3130 - 3137
[4] Ann. Inst. Pasteur, 1930, vol. 44, p. 719,737

3
[ 1810-67-9 ]
[ 1810-72-6 ]

Reference： [1] ACS Medicinal Chemistry Letters, 2017, vol. 8, # 10, p. 1019 - 1024
[2] Patent: US2008/234319, 2008, A1, . Location in patent: Page/Page column 11-12

4
[ 503-38-8 ]
[ 1810-72-6 ]

Reference： [1] Journal of Organic Chemistry, 2002, vol. 67, # 22, p. 7884 - 7886

5
[ 116035-66-6 ]
[ 1810-72-6 ]

Reference： [1] Journal of Organic Chemistry, 2002, vol. 67, # 22, p. 7884 - 7886

6
[ 19358-40-8 ]
[ 1810-72-6 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 14, p. 1559 - 1562

7
[ 1219101-01-5 ]
[ 1810-72-6 ]
[ 1219101-08-2 ]

Reference： [1] Heterocycles, 2010, vol. 81, # 2, p. 305 - 316

8
[ 1219101-01-5 ]
[ 1810-72-6 ]
[ 1219101-11-7 ]

Reference： [1] Heterocycles, 2010, vol. 81, # 2, p. 305 - 316

9
[ 79044-04-5 ]
[ 1810-72-6 ]

Reference： [1] Journal of Organic Chemistry, 2002, vol. 67, # 22, p. 7884 - 7886

10
[ 612-57-7 ]
[ 1810-72-6 ]

Reference： [1] Journal of Organic Chemistry, 1944, vol. 9, p. 302,305, 309
[2] European Journal of Organic Chemistry, 2016, vol. 2016, # 8, p. 1606 - 1611

11
[ 106-47-8 ]
[ 1810-72-6 ]

Reference： [1] ACS Medicinal Chemistry Letters, 2017, vol. 8, # 10, p. 1019 - 1024

12
[ 553-03-7 ]
[ 1810-72-6 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 14, p. 1559 - 1562

13
[ 6563-10-6 ]
[ 1810-72-6 ]
[ 4203-18-3 ]

Reference： [1] Journal of Organic Chemistry, 1944, vol. 9, p. 302,305, 309
[2] Medicinal Chemistry Research, 2014, vol. 23, # 7, p. 3468 - 3477

14
[ 53691-91-1 ]
[ 1810-72-6 ]

Reference： [1] ACS Medicinal Chemistry Letters, 2017, vol. 8, # 10, p. 1019 - 1024

[ 1810-72-6 ] Synthesis Path-Downstream 1~88

1
[ 6563-10-6 ]
[ 1810-72-6 ]
[ 4203-18-3 ]

Reference： [1]Journal of Organic Chemistry,1944,vol. 9,p. 302,305, 309
[2]Medicinal Chemistry Research,2014,vol. 23,p. 3468 - 3477

2
[ 1810-72-6 ]
(R)-7-chloro-2-phenyl-2,3-dihydroimidazo[1,2-a]quinoline [ No CAS ]

Reference： [1]Tetrahedron,2006,vol. 62,p. 285 - 294
[2]Organic Letters,2005,vol. 7,p. 3445 - 3447

3
[ 116035-66-6 ]
[ 1810-72-6 ]

Reference： [1]Journal of Organic Chemistry,2002,vol. 67,p. 7884 - 7886

4
[ 79044-04-5 ]
[ 1810-72-6 ]

Reference： [1]Journal of Organic Chemistry,2002,vol. 67,p. 7884 - 7886

5
(E)-N-(4-chlorophenyl)-3-ethoxypropenamide [ No CAS ]
[ 1810-72-6 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3130 - 3137

6
[ 1810-72-6 ]
[ 78060-46-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2000,vol. 10,p. 1559 - 1562
[2]Patent: US2014/142114,2014,A1

7
[ 553-03-7 ]
[ 1810-72-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2000,vol. 10,p. 1559 - 1562

8
[ 1810-72-6 ]
methyl 2-{4-[N-(6-chloroquinolin-2-yl)-N-methylamino]-phenoxy}propionate [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,1997,vol. 7,p. 1489 - 1492

9
[ 1810-72-6 ]
[ 120614-30-4 ]

Reference： [1]Patent: US2861076,1957,

10
[ 1810-72-6 ]
5-bromo-2,6-dichloroquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%		intermediate a) Preparation of Bromine (5.2 mL, 101 mmol) was added dropwise over a period of 30 min. to <strong>[1810-72-6]2,6-dichloroquinoline</strong> (20 g, 101 mmol) and aluminum chloride (40 g, 303 mmol) at 120 0C. The resulting mixture was stirred at 120 0C for 1 hour, cooled to rt and methanol/water (1 : 1 v:v, 150 mL) was slowly added. The methanol was removed under reduced pressure and the resulting slurry was extracted with DCM. The organic <n="48"/>phases were combined, washed with saturated aqueous sodium bicarbonate, dried with Na2SO4, filtered, concentrated and purified by flash column chromatography (30-100% DCM in hexanes) to provide the desired product (23 g, 83%). 1H NMR (500 MHz, CDCl3) delta 8.51 (dd, J= 8.9, 0.7, IH), 7.92 (dd, J= 9.0, 0.7, IH), 7.76 (dd, J= 8.9, 4.2, IH), 7.49 (d, J= 8.6, IH).
82%		[00210] A mixture of 2, 6-dichloroquinoline(5.0 g, 25.4 mmol) and aluminiumtrichloride (10.0 g, 76.1 mmol) was heated to 120 oc with stirring under a nitrogenatmosphere. Bromine (4.81 g, 30.48 mmol, 1.54 mL) was added dropwjse over 0.5 h, and the mixture was then stirred at 120 oc for 1 hour before being cooled to room temperature. A MeOH/ water mixture (50 mL,1:1) wasthen slowly added and the mixture was concentrated in vacuum. Dichloromethane (500 mL) and water (250 mL) were added, the organic layerswere separated and the aqueousfraction vvas extracted with dichloromethane(2 x 50 mL). The combinedorganic extracts were washed withsaturated aqueous sodiumhydrogen carbonate (150 mL) before being dried, filtered andconcentrated. Purification by column chromatography on silica gel (petroleum ether:EtOAc = 10:1) gave 5-bromo-<strong>[1810-72-6]2,6-dichloroquinoline</strong> (5.7 g, 82%) as a solid. mlz: 275.2 [M + H] +
	With aluminum (III) chloride; bromine; at 120℃; for 2h;	Example 15; 4-[6-Chloro-5-[[(2-tricyclo[3.3.1.13'7]dec-l-ylethyl)amino]carbonyl]-2-quinoIinyl]-l- piperazinepropanoic acid, methyl ester; a) 5-Bromo-<strong>[1810-72-6]2,6-dichloro-quinoline</strong>; <strong>[1810-72-6]2,6-Dichloroquinoline</strong> (30 g) and aluminium trichloride (60 g) were heated to 12O0C with stirring under a nitrogen atmosphere. Bromine (9.2 mL) was added dropwise over 1 hour and the mixture was then stirred at 12O0C for 1 hour before being cooled to room temperature. A methanol / deionised water mixture (150 mL, 1:1) was then slowly added and the mixture was concentrated in vacuo. Dichloromethane (500 mL) and deionised water (250 mL) were added, the layers were separated and the aqueous fraction was extracted with dichloromethane (2 x 250 mL). The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate (250 mL) before being dried, filtered and concentrated. Purification by chromatography (SiC>2, isohexane: dichloromethane 7:3 as eluant) gave the sub-title compound as a solid (27 g).1H NMR (400 MHz, CDCl3) delta 8.53 (IH, d), 7.94 (IH, d), 7.78 (IH, d), 7.50 (IH, d). MS: APCI(+ve) 276/278/280/282 (M+H"1").

		<strong>[1810-72-6]2,6-Dichloroquinoline</strong> (30 g) and aluminium trichloride (60 g) were heated to 120C with stirring under a nitrogen atmosphere. Bromine (9.2 mL) was added dropwise over 1 hour and the mixture was then stirred at 120C for 1 hour before being cooled to room temperature. A methanol/deionised water mixture (150 ML, 1: 1) was then slowly added and the mixture was concentrated IN VACUO. Dichloromethane (500 mL) and deionised water (250 mL) were added, the layers were separated and the aqueous fraction was extracted with dichloromethane (2 x 250 mL). The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate (250 mL) before being dried, filtered and concentrated. Purification by chromatography (SI02, isohexane: dichloromethane 7: 3 as eluant) gave the title compound as a solid (27 g). 1H NMR (400 MHz, CDC13) 6 8.53 (1H, d), 7.94 (1H, d), 7.78 (1H, d), 7.50 (1H, d). MS: APCI (+ve) 276/278/280/282 (M+H+).
	With aluminum (III) chloride; bromine; at 120℃; for 2h;	a) 5-Bromo-2, 6-dichloro-quinoline 2, 6-DICHLOROQUINOLINE (30 g) and aluminium trichloride (60 g) were heated to 120C with stirring under a nitrogen atmosphere. Bromine (9.2 mL) was added dropwise over 1 hour and the mixture was then stirred at 120C for 1 hour before being cooled to room temperature. A METHANOL/DEIONISED water mixture (150 mL, 1: 1) was then slowly added and the mixture was concentrated in vacuo. Dichloromethane (500 mL) and deionised water (250 mL) were added, the layers were separated and the aqueous fraction was extracted with dichloromethane (2 x 250 ML). The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate (250 mL) before being dried, filtered and concentrated. Purification by chromatography (SI02, isohexane: dichloromethane 7: 3 as eluant) gave the sub-title compound as a solid (27 g). 'H NMR (400 MHz, CDCL3) 8 8.53 (1H, d), 7.94 (1H, d), 7.78 (1H, d), 7.50 (1H, d). MS: APCI (+ve) 276/278/280/282 (M+H+).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 4781 - 4784
[2]Patent: WO2009/132000,2009,A1 .Location in patent: Page/Page column 45-46
[3]Patent: WO2015/187905,2015,A1 .Location in patent: Paragraph 00210
[4]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 1660 - 1664
[5]Patent: WO2006/59945,2006,A1 .Location in patent: Page/Page column 57
[6]Patent: WO2004/106305,2004,A1 .Location in patent: Page 143-144
[7]Patent: WO2005/9968,2005,A1 .Location in patent: Page/Page column 62-63

11
[ 1810-72-6 ]
[ 3385-21-5 ]
[ 1000417-94-6 ]

Yield	Reaction Conditions	Operation in experiment
36.3%	With pyridine; for 48h;Heating / reflux;	a) N-(6-chloroquinolin-2-yl) cyclohexane-1, 3-diamine; <strong>[1810-72-6]2,6-dichloroquinoline</strong> (198 mg, 1.0 mmol, ) and cyclohexane-1, 3-diamine (457 mg, 4.0 mmol) were refluxed in pyridine (10 mL) for 48 h. The solvent was evaporated and the residue was purified on a pre-packed SiO2-column (Isolute, 10 g) eluted with DCM: MeOH (containing 1 % NH40H aq) 10: 1 to yield 100 mg (36. 3 %) of the title compound. IH NMR (500 MHz, MeOH-d4) 8 7.72-7. 67 (m, 1H), 7.55-7. 50 (m, 2H), 7.41-7. 38 (m, 1H), 6.80 (d, 1H, minor isomer), 6.71 (d, 1H, major isomer), 4.38 (bs, 1H, minor isomer), 3.98 (m, 1H, major isomer), 3.04 (m, 1H, minor isomer), 2.79 (m, 1H, major isomer), 2.25-1. 01 (m, 8H).

Reference： [1]Patent: WO2005/66132,2005,A1 .Location in patent: Page/Page column 55

12
[ 1810-72-6 ]
[ 4521-31-7 ]
[ 889686-91-3 ]

Yield	Reaction Conditions	Operation in experiment
9%	With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 60℃; for 20h;	Step 1: {2-r(6-Chloroquinolin-2-yl)thio1phenyl}methanol; A mixture of 2-mercaptobenzyl alcohol (1.78 g, 12.7 mmol), <strong>[1810-72-6]2,6-dichloroquinoline</strong> (2.48 g, 12.5 mmol) and potassium carbonate (1.73 g, 12.5 mmol) in N,N-dimethylformamide (25 mL) was stirred at room temperature under nitrogen for 3 hours, then at 600C for 17 hours. The cooled reaction mixture was poured into water and extracted with ethyl acetate (x2). The combined organic layers were washed with brine, dried over MgSO4 and evaporated. The residue was purified by flash column chromatography on silica, EPO <DP n="26"/>eluting with 5-10% ethyl acetate/dichloromethane, to give {2-[(6-chloroquinolin-2-yl)thio]phenyl}methanol (0.37 g, 9%) as a colourless oil. 1H NMR (400 MHz, CDCl3) delta 7.84 (1 H, d, J = 8.7 Hz), 7.72-7.66 (4 H, m), 7.55-7.51 (2 H, m), 7.39-7.35 (1 H, m), 7.19 (1 H, dd, J = 1.2, 8.7 Hz), 4.84 (2 H, s), 3.78 (1 H, s); m/z (ES+) 302, 304 [MH+].

Reference： [1]Patent: WO2006/59149,2006,A1 .Location in patent: Page/Page column 24-25

13
[ 1810-72-6 ]
[ 1193-02-8 ]
[ 190331-33-0 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; In hexane;	<strong>[1810-72-6]2,6-Dichloroquinoline</strong> (15.2 moles, 3.0 g), 4-aminothiophenol (15.2 moles, 1.9 g), and DMAP (15.2 moles, 1.85 g) were stirred at room temperature for 3 days. The solvent was removed, diluted with ethyl acetate, washed with water, dried over sodium sulfate and concentrated. The product was purified by HPLC over silica gel eluted with 25% ethyl acetate in hexane to yield 2-(4-aminophenylthio)-6-chloroquinoline 830 mg, 19%. Mass spec (FD) 286. Calculated for C15 H11 ClN2 S: C, 62.82 H, 3.87; N, 9.77. Found: C, 63.09; H, 3.94; N, 9.61.
	With dmap; In hexane;	<strong>[1810-72-6]2,6-Dichloroquinoline</strong> (15.2 mmoles, 3.0 g), 4-aminothiophenol (15.2 mmoles, 1.9 g), and DMAP 15.2 mmoles, 1.85 g) were stirred at room temperature for 3 days. The solvent was removed, diluted with ethyl acetate, washed with water, dried over sodium sulfate and concentrated. The product was purified by HPLC over silica gel eluted with 25% ethyl acetate in hexane to yield 2-(4-aminophenylthio)-6-chloroquinoline 830 mg, 19%. Mass spec (FD) 286. Calculated. for C15 H11 ClN2 S: C, 62.82H, 3.87; N, 9.77. Found: C, 63.09; H, 3.94; N, 9.61.

Reference： [1]Patent: US5624937,1997,A
[2]Patent: US5814646,1998,A

14
[ 1810-72-6 ]
[ 115778-33-1 ]
4-(4-((6-chloro-2-quinolinyl)oxy)phenoxy)-2-penten-1-ol [ No CAS ]
[ 21335-55-7 ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide;	EXAMPLE 2 E-isomer of 4-(4-((6-chloro2-quinolinyl)oxy)phenoxy)-2-penten-1-ol STR15 A mixture of 3.06 g (15.4 mmol) of <strong>[1810-72-6]2,6-dichloroquinoline</strong>, 3.00 g (15.4 mmol) of (E)-4-(4-hydroxyphenoxy)-2-penten-1-ol, 2.34 g (16.9 mmol) of powdered, anhydrous potassium carbonate and 50 ml of dry dimethylsulfoxide was warmed at 100-110 C. for a period of 6 hours. The mixture was cooled to room temperature, poured over ice and extracted three times with ether. The combined ether layers were washed once with 1 percent aqueous sodium hydroxide then with water, dried over MgSO4 and evaporated to dryness. The residue was purified by preparative scale HPLC, eluding with 72:28 hexane:acetone, and then thoroughly dried to leave 2.9 g of the desired pentenol as a brown gum. (Compound B).

Reference： [1]Patent: US4900354,1990,A

15
[ 1810-72-6 ]
[ 42516-28-9 ]
[ 106-47-8 ]
[ 124466-72-4 ]

Yield	Reaction Conditions	Operation in experiment
		(2E,4E)-N-Isobutyl 12-(6-chloro-2-quinolinyloxy) dodeca-2,4-dienamide Starting from <strong>[1810-72-6]2,6-dichloroquinoline</strong> (prepared as for compound 23 starting from 4-chloroaniline (ex. Aldrich)) and using triethyl 4-phosphonocrotonate.

Reference： [1]Patent: US5114940,1992,A

16
[ 1810-72-6 ]
[ 115778-33-1 ]
4-(4-((6-chloro-2-quinolinyl)oxy)phenoxy)-2-penten-1-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In dimethyl sulfoxide;	EXAMPLE 2 E isomer of 4-(4-((6-chloro-2-quinolinyl)oxy)phenoxy)-2-penten-1-ol STR54 A mixture of 1.58 g (8 mmol) of <strong>[1810-72-6]2,6-dichloroquinoline</strong>, 1.75 g (9 mmol) of (E)-4-(4-hydroxyphenoxy)-2-penten-1-ol, 1.52 g (11 mmol) of powdered, anhydrous potassium carbonate and 30 ml of dry dimethylsulfoxide was warmed under nitrogen at 110 C. for a period of 5 hours. The mixture was cooled to room temperature, poured into ice cold 1 percent aqueous sodium hydroxide, and the resulting aqueous mixture was extracted three times with ether. The combined ether layers were washed once with 1 percent aqueous sodium hydroxide and twice with water, dried over MgSO4 and evaporated to dryness. The residue was purified by preparative scale HPLC, eluding with 7:3 hexane:ethyl acetate, and then thoroughly dried to leave 1.71 g (60%) of desired pentanol as a yellow, viscous gum.

Reference： [1]Patent: US4731108,1988,A

17
[ 1810-72-6 ]
[ 123-30-8 ]
4-[N-(6-chloro-2-quinolinyl)-amino]phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In ethanol;	(a) A mixture of <strong>[1810-72-6]2,6-dichloroquinoline</strong> (6.0 g), 4-aminophenol (3.3 g), hydrochloric acid (3 g) and ethanol (100 ml) was stirred and refluxed for 10 hours. The solvent was removed under reduced pressure and the residue partitioned between ethyl acetate and water. The ethyl acetate extracts on evaporation gave 4-[N-(6-chloro-2-quinolinyl)-amino]phenol (2.7 g) as a brown solid.

Reference： [1]Patent: US4444584,1984,A

18
[ 1810-72-6 ]
[ 20872-28-0 ]
ethyl 2-[4-(6-chloroquinolin-2-yloxy)phenoxy]acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 15 Ethyl 2-[4-(6-chloroquinolin-2-yloxy)phenoxy]acetate (35) was prepared from <strong>[1810-72-6]2,6-dichloroquinoline</strong> and ethyl 2-(4-hydroxyphenoxy) acetate following essentially the same procedure as that described in Example 1. The compound was isolated as a colourless solid, mp 95 C.

Reference： [1]Patent: US4444584,1984,A

19
[ 1810-72-6 ]
[ 51-72-9 ]
[ 78864-94-5 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; water;	(a) A mixture of <strong>[1810-72-6]2,6-dichloroquinoline</strong> (1.1 g; prepared according to the method of O Fischer, Chem. Ber., 35, 3683 (1902), 4-(N-methylamino)phenol sulfate (1.5 g), ethanol (5 ml) and water (20 ml) was heated under reflux for a period of 24 hours. Water (50 ml) was added to the mixture and the aqueous mixture was extracted with chloroform (2*100 ml). The chloroform extracts were dried (anhydrous MgSO4) and the solvent was evaporated to give 4-[N-(6-chloro-2-quinolinyl)-N-methylamino]phenol (1.1 g) as a dark oil. Proton magnetic resonance spectrum (CDCl3; delta in ppm): 8.0-6.6 and 7.2 (10H, m and d of d, quinoline, hydroxy and phenyl protons); 3.6 (3H, s, N--CH3).

Reference： [1]Patent: US4444584,1984,A

20
[ 1810-72-6 ]
[ 42806-90-6 ]
ethyl 2-methyl-2-[4-(6-chloroquinolin-2-yloxy)phenoxy]-propionate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 9 Ethyl 2-methyl-2-[4-(6-chloroquinolin-2-yloxy)phenoxy]-propionate (36) was prepared from <strong>[1810-72-6]2,6-dichloroquinoline</strong> and ethyl 2-methyl-2-(4-hydroxyphenoxy)propionate following essentially the same procedure as that described in Example 1. The product was isolated after chromatography as a low melting point solid. Mass spectrum (m/e): 385 (parent ion; 30%); 312 (35%); 271 (100%); 270 (100).

Reference： [1]Patent: US4444584,1984,A

21
[ 1810-72-6 ]
[ 1011533-15-5 ]
[ 1222702-83-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 629 - 633

22
[ 1810-67-9 ]
[ 1810-72-6 ]

Yield	Reaction Conditions	Operation in experiment
		a) 2,6-Dichloroquinoline; Phosphorus oxychloride (16.72 Kg) was charged to a vessel containing 6-chloroquinolin-2(1H)-one (12.50 Kg) (Prepared according to method of Johnston K. M. et al., J. Chem. Soc. Perkin Trans. 1, 1972, 1648 and references therein), benzyltrimethylammonium chloride (1.575 Kg) and 1,2-dimethoxyethane (87.8 Kg) at 70 C. 1,2-dimethoxyethane (22.5 Kg) was charged as a line rinse. The reaction was stirred at 70 C. to 75 C. for ca. 6 hours before the batch was concentrated to ca. 44 L by vacuum distillation (<40 C.). The concentrate was diluted with dichloromethane (253.1 Kg), adjusted to 38 C. to 45 C. and quenched by the addition of water (37.5 Kg) whilst maintaining the temperature at 38 C. to 45 C. After 70 minutes the batch was cooled to 25 C. to 30 C. and treated with Celite (1.30 Kg) for 40 minutes. The slurry was pressure filtered via a 1 mum filter membrane and the filtrates diluted with dichloromethane (87.5 Kg). The phases were separated and the aqueous phase extracted twice with dichloromethane (82 Kg). The combined organic extracts were washed sequentially with 5% w/w sodium hydrogen carbonate solution (37 L), water (37 Kg) and then concentrated to ca. 75 L at 25 C. to 40 C. Isopropanol (96.5 Kg) was charged and the batch then concentrated to ca. 75 L at 25 C. to 40 C. Isopropanol (95.4 Kg) was charged and the batch then concentrated to ca. 75 L at 25 C. to 40 C. The resultant slurry was stirred at 16 C. to 18 C. for 2 hours and then filtered. The filter cake was washed with isopropanol (19.7 Kg) at ca. 20 C. and then dried at up to 50 C. in vacuo to provide the subtitle compound as an off white solid (12.04 Kg).1H NMR delta(DMSO) 8.45 (1H, d), 8.22 (1H, d), 7.99 (1H, d), 7.86 (1H, dd), 7.68 (1H, d).

Reference： [1]ACS Medicinal Chemistry Letters,2017,vol. 8,p. 1019 - 1024
[2]Patent: US2008/234319,2008,A1 .Location in patent: Page/Page column 11-12

23
[ 1810-72-6 ]
[ 1061222-04-5 ]

Yield	Reaction Conditions	Operation in experiment
		b) 2,6-Dichloro-5-iodoquinoline; <strong>[1810-72-6]2,6-Dichloroquinoline</strong> (12.04 Kg) was charged to trifluoromethanesulphonic acid (80.6 Kg) in ten approximately equal portions such that the temperature was maintained at 15 C. to 25 C. N-iodosuccinimide (13.74 Kg) was then charged in five approximately equal portions such that the temperature was maintained at 15 C. to 25 C. The reaction was stirred at 20 C. to 25 C. for ca. 36 hours. The temperature was adjusted to 15 C. to 20 C., diluted with dichloromethane (159.4 Kg), adjusted to 5 C. to 10 C. and quenched by the addition of water (96.5 Kg) whilst maintaining the temperature at 5 C. to 23 C. The slurry was clarified via a 1 mum filter membrane and line rinsed with dichloromethane (16.1 Kg). The phases were separated and the aqueous phase extracted with dichloromethane (48.2 Kg). The combined organic extracts were washed with 5% w/w sodium hydrogen carbonate solution (48 L). The sodium hydrogen carbonate phase was back extracted with dichloromethane (15.4 Kg). The combined organic extracts were washed with 20% w/w sodium thiosulphate solution (48 L). The sodium thiosulphate phase was back extracted with dichloromethane (16.3 Kg). The combined organic extracts were washed with water (47 L). The water phase was back extracted with dichloromethane (16.4 Kg). The combined organic extracts were recharged to the vessel, line rinsed with dichloromethane (31.3 Kg) and concentrated to ca. 48 L at atmospheric pressure. Dichloromethane (63 Kg) was charged and the batch concentrated to ca. 48 L at atmospheric pressure.Dichloromethane (66 Kg) was charged and the batch concentrated to ca. 48 L at atmospheric pressure. Dichloromethane (63.6 Kg) was charged and the batch concentrated to ca. 48 L at atmospheric pressure. Dichloromethane (63.8 Kg) was charged and the batch concentrated to ca. 48 L at atmospheric pressure. Dichloromethane (77.8 Kg) was charged and the batch concentrated to ca. 48 L at atmospheric pressure. Acetonitrile (47.7 Kg) was charged and the batch concentrated to ca. 96 L at atmospheric pressure. Acetonitrile (46.4 Kg) was charged and the batch concentrated to ca. 96 L at atmospheric pressure. The batch was cooled to 18 C. to 23 C., stirred for 2.5 hours and then filtered. The filter cake was washed twice with acetonitrile (19.6 Kg) at ca. 20 C. and then dried at up to 55 C. in vacuo to provide the subtitle compound as a pale yellow solid (16.74 Kg).1H NMR delta(DMSO) 8.51 (1H, d), 8.01-7.94 (2H, m), 7.72 (1H, d).

Reference： [1]Patent: US2008/234319,2008,A1 .Location in patent: Page/Page column 12

24
[ 1810-72-6 ]
[ 860434-15-7 ]
C₃₁H₃₀ClN₃O₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 4232 - 4241

25
[ 109-01-3 ]
[ 1810-72-6 ]
[ 79489-60-4 ]

Yield	Reaction Conditions	Operation in experiment
		Example 6; 6-Chloro-2-(4-methyl-piperazinyl)-quinoline (VUF6959); <strong>[1810-72-6]2,6-Dichloroquinoline</strong> (300 mg) was added to N-methylpiperazine (2.0 mL) and was heated in the microwave at 160 C. for 5 min. After completion the obtained solution was evaporated to dryness, the residue was dissolved in EtOAc and then washed with saturated NaHCO3 solution. The organic layer was dried with brine and Na2SO4. The product was recrystallised from EtOAc/Et2O. Mp 141.1-142.5 C.; 1H-NMR (DMSO): delta (ppm) 7.73 (d, J=9.2 Hz, 1H), 7.55 (d, J=8.9 Hz, 1H), 7.49 (d, J=2.3 Hz, 1H), 7.38 (dd, J=2.4 Hz, J=8.9 Hz, 1H), 6.92 (d, J=9.2 Hz, 1H), 3.69 (t, J=5.1 Hz, 4H), 2.48 (t, J=5.1 Hz, 4H), 2.29 (s, 3H).

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 2457 - 2467
[2]Patent: US2010/16293,2010,A1 .Location in patent: Page/Page column 11

26
[ 110-91-8 ]
[ 1810-72-6 ]
[ 34500-42-0 ]

Yield	Reaction Conditions	Operation in experiment
80%	With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 3h;	To a solution of commercially available <strong>[1810-72-6]2,6-dichloroquinoline</strong> (0.5 g, 2.52 mmol) in dry DMF (5 mL) was added potassium carbonate (1 g, 7.52 mmol) and morpholine (0.32 g, 3.78 mmol). The reaction mixture was heated to 100 C for 3 hours. The reaction mixture was concentrated under vacuo and the crude reaction mixture was purified on a silica gel column using a Biotage Isolera One purification system employing an EtOAc/hexane gradient (10/80 => 80/20) to afford the title compound as a pale yellow solid (500 mg, 80 %). (0676) MS: 249.1 (M+H)+ (0677) 1H-NMR (400 MHz, DMSO-d6) d = 8.06 (d, J = 12.40 Hz, 1 H), 7.84 (d, J = 2.40 Hz, 1 H), 7.51- 7.52 (m, 2H), 7.31 (d, J = 12.40 Hz, 1 H), 3.66-3.67 (m, 8H).

Reference： [1]Patent: WO2019/134978,2019,A1 .Location in patent: Page/Page column 108; 109
[2]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4199 - 4203

27
[ 1810-72-6 ]
[ 1758-46-9 ]
[ 1136478-92-6 ]

Yield	Reaction Conditions	Operation in experiment
73%	at 120℃; for 1h;microwave;	<strong>[1810-72-6]2,6-Dichloroquinoline</strong> (1.0 g, 5.1 mmol) and 2-phenoxyethylamine (1.5 g, 11 mmol) were microwaved at 120 C. for 1 h. The reaction mixture was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 100:0?70:30 gradient). (6-Chloro-quinolin-2-yl)-(2-phenoxy-ethyl)-amine was obtained as a light yellow solid (1.1 g, 73%), MS: m/e=299.3 (M+H+).
73%	at 120℃; for 1h;Irradiation;	Step A: A stirred mixture of <strong>[1810-72-6]2,6-dichloro-quinoline</strong> (1.0 g, 5.1 mmol) and 2-phenoxyethylamine (1.5 g, 11 mmol) was heated in the microwave for 1 h at 120 C. Purification by flash chromatography on silica gel (ethyl acetate/heptane 100:0?70:30) yielded (6-chloro-quinolin-2-yl)-(2-phenoxy-ethyl)-amine as a light yellow oil (1.1 g, 73%), MS: m/e=299.3 (M+H+).

Reference： [1]Patent: US2009/88451,2009,A1 .Location in patent: Page/Page column 14
[2]Patent: US2009/233927,2009,A1 .Location in patent: Page/Page column 8

28
[ 1810-72-6 ]
[ 10277-74-4 ]
[ 1186369-61-8 ]

Yield	Reaction Conditions	Operation in experiment
34%	at 125℃; for 16h;	A stirred mixture of <strong>[1810-72-6]2,6-dichloro-quinoline</strong> (4.8 g, 24 mmol) and (R)-1-aminoindane (6.5 g, 48 mmol) was heated in a sealed tube for 16 h at 125 C. Purification by flash chromatography on silica gel (ethyl acetate/heptane) yielded (6-chloro-quinolin-2-yl)-(R)-indan-1-yl-amine as a yellow solid (2.4 g, 34%), MS 295.1 [(M+H)+].
30%	at 125℃; for 20h;	Step A: <strong>[1810-72-6]2,6-Dichloroquinoline</strong> (5.0 g, 25 mmol) and R-(-)-1-aminoindane (6.725 g, 50 mmol) were heated at 125 C. for 20 h. The reaction mixture was purified by flash chromatography on silica gel (heptane/ethyl acetate 100:0?70:30 gradient). (6-Chloro-quinolin-2-yl)-(R)-indan-1-yl-amine was obtained as a light red solid (2.25 g, 30%), MS: m/e=296.8 (M+H+).

Reference： [1]Patent: US2009/227583,2009,A1 .Location in patent: Page/Page column 13
[2]Patent: US2009/227570,2009,A1 .Location in patent: Page/Page column 10-11; 15

29
[ 95-14-7 ]
[ 1810-72-6 ]
[ 1150313-07-7 ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 2979 - 2988

30
[ 1810-72-6 ]
2-(4-hydroxy-2,6-dimethylphenyl)-4-(tetrahydropyran-4-ylmethyl)-cyclopentane-1,3-dione [ No CAS ]
2-[4-(6-chloroquinolin-2-yloxy)-2,6-dimethylphenyl]-4-(tetrahydropyran-4-ylmethyl)cyclopentane-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 140℃; for 0.666667h;Microwave irradiation;	Step 5 : Preparation of 2-[4-(6-chloroquinolin-2-yloxy)-2,6-dimethylphenyl]-4-(tetrahydropyran-4- ylmethyl)cyclopentane-1 ,3-dioneA suspension of 2-(4-hydroxy-2,6-dimethylphenyl)-4-(tetrahydropyran-4-ylmethyl)cyclopentane- 1 ,3-dione (0.104g, 0.00033mol), <strong>[1810-72-6]2,6-dichloroquinoline</strong> (0.065g, 0.00033mol) and potassium carbonate (0.14Og, 0.00101 mol) in anhydrous Lambda/,Lambda/-dimethylformamide (3ml) is heated at 140C for 40 minutes under microwave irradiation. After cooling to room temperature the reaction mixture was quenched with 2M hydrochloric acid and extracted with ethyl acetate. The organic phase is separated, washed with distilled water then dried over anhydrous magnesium sulfate. The mixture is filtered, the filtrate is evaporated in vacuo and the residue is purified by preparative reverse phase HPLC to afford 2-[4-(6-chloroquinolin-2-yloxy)-2,6-dimethylphenyl]-4- (tetrahydropyran-4-ylmethyl)cyclopentane-1 ,3-dione.

Reference： [1]Patent: WO2010/89210,2010,A1 .Location in patent: Page/Page column 65-66

31
[ 1810-72-6 ]
[ 17356-08-0 ]
C₁₀H₈ClN₃S*ClH [ No CAS ]

Reference： [1]Heterocycles,2010,vol. 81,p. 305 - 316
[2]Medicinal Chemistry Research,2014,vol. 23,p. 3468 - 3477

32
[ 1810-72-6 ]
[ 74-88-4 ]
[ 5188-07-8 ]
[ 75-18-3 ]
[ 54002-20-9 ]

Reference： [1]Heterocycles,2010,vol. 81,p. 305 - 316

33
[ 1810-72-6 ]
[ 5188-07-8 ]
[ 75-18-3 ]
[ 110131-14-1 ]

Reference： [1]Heterocycles,2010,vol. 81,p. 305 - 316

34
[ 1219101-01-5 ]
[ 1810-72-6 ]
[ 1219101-08-2 ]

Reference： [1]Heterocycles,2010,vol. 81,p. 305 - 316

35
[ 1219101-01-5 ]
[ 1810-72-6 ]
[ 1219101-11-7 ]

Reference： [1]Heterocycles,2010,vol. 81,p. 305 - 316

36
[ 1810-72-6 ]
[ 147621-18-9 ]
[ 1322717-04-3 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 7220 - 7231

37
[ 1810-72-6 ]
[ 1239320-28-5 ]
[ 1239320-29-6 ]

Reference： [1]Patent: US2011/319381,2011,A1

38
[ 1810-72-6 ]
[ 1239320-28-5 ]
[ 1239320-27-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In dimethylsulfoxide-d6; at 130℃; for 12h;Sealed tube;	14.5 Ethyl[7-(6-chloroquinolin-2-yl)-7-azaspiro[3.5]non-2-yl]carbamate 0.166 g (0.78 mmol) of ethyl(7-azaspiro[3.5]non-2-yl)carbamate, obtained in the preceding step and used in base form, 0.155 g (0.78 mmol) of <strong>[1810-72-6]2-chloro-6-chloroquinoline</strong> and 0.113 g (0.82 mmol) of potassium carbonate in 2 mL of DMSO are placed in a sealed tube. The mixture is then heated at 130 C. for 12 hours. The reaction mixture is allowed to cool to room temperature and is then taken up in dichloromethane and water. The aqueous phase is separated out and extracted twice with dichloromethane, the combined organic phases are washed with saturated aqueous ammonium chloride solution and dried over sodium sulfate, and the filtrate is concentrated under reduced pressure. After evaporating off the solvent, the residue obtained is purified by chromatography on silica gel, eluting with a 98/2/0.2 mixture of dichloromethane, methanol and 28% aqueous ammonia. 0.151 g of pure product is thus obtained in the form of a powder. LC-MS: M+H=374 m.p. ( C.): 137-139 1H NMR (CDCl3) delta (ppm): 7.80 (d, 1H); 7.70 (m, 1H); 7.60 (m, 1H); 7.50 (m, 1H); 7.10 (d, 1H); 4.80 (broad s, 1H); 4.20 (m, 3H); 3.70 (m, 4H); 2.50 (m, 2H); 1.90-1.60 (m, 6H); 1.30 (t, 3H).

Reference： [1]Patent: US2011/319381,2011,A1 .Location in patent: Page/Page column 20

39
[ 1810-72-6 ]
[ 165528-81-4 ]
[ 1227245-60-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In methanol; dichloromethane; dimethyl sulfoxide; at 130℃; for 12h;Sealed tube;	11.1. tert-Butyl {2-[1-(6-chloroquinolin-2-yl)piperidin-4-yl]-ethyl}carbamate 2.00 g (8.76 mmol) of (commercial), 1.73 g (8.76 mmol) of <strong>[1810-72-6]2,6-dichloroquinoline</strong> (commercial) and 1.27 g (36.79 mmol) of potassium carbonate in 11 mL of DMSO are introduced into a sealed tube. The mixture is then heated at 130 C. for 12 hours. The reaction mixture is allowed to cool to room temperature and then taken up in dichloromethane and water. The aqueous phase is separated out and extracted twice with dichloromethane, and the combined organic phases are washed with saturated aqueous ammonium chloride solution and dried over sodium sulfate, and the filtrate is concentrated under reduced pressure. After evaporating off the solvent, the residue obtained is purified by chromatography on silica gel, eluting with a 98/2/0.2 mixture of dichloromethane, methanol and 28% aqueous ammonia. 3.40 g of pure product are obtained in the form of a powder. LC-MS: M+H=390 m.p. ( C.): 120-122 C. 1H NMR (CDCl3) delta (ppm): 7.80 (d, 1H); 7.65 (d, 1H); 7.60 (s, 1H); 7.40 (d, 1H); 7.00 (d, 1H); 4.50 (broad d, 3H); 3.25 (m, 2H); 2.90 (m, 2H); 1.90 (d, 2H); 1.65 (m, 1H); 1.45 (m, 11H); 1.25 (m, 2H).

Reference： [1]Patent: US2012/15950,2012,A1 .Location in patent: Page/Page column 14

40
[ 1810-72-6 ]
[ 1206673-56-4 ]

Reference： [1]Patent: US2012/15950,2012,A1

41
[ 1810-72-6 ]
[ 1227244-84-9 ]

Reference： [1]Patent: US2012/15950,2012,A1

42
[ 1810-72-6 ]
[ 1227245-17-1 ]

Reference： [1]Patent: US2012/15950,2012,A1

43
[ 1810-72-6 ]
[ 1227245-35-3 ]

Reference： [1]Patent: US2012/15950,2012,A1

44
[ 1810-72-6 ]
[ 1227245-71-7 ]
[ 1227245-20-6 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 120℃; for 12h;Sealed tube;	14.4. Ethyl 5-[1-(6-chloroquinolin-2-yl)-4-fluoropiperidin-4-ylmethylcarbamoyloxymethyl]isoxazole-3-carboxylate 0.465 g (1.05 mmol) of ethyl 5-(4-fluoropiperidin-4-ylmethylcarbamoyloxymethyl)isoxazole-3-carboxylate trifluoroacetate, obtained in step 14.3., 0.23 g (1.15 mmol) of <strong>[1810-72-6]2,6-dichloroquinoline</strong> and 730 muL (4.20 mmol) of N,N-diisopropylethylamine in 5 mL of acetonitrile are introduced into a sealed tube. The mixture is then heated at 120 C. for 12 hours. The mixture is allowed to cool to room temperature and the reaction medium is then taken up in ethyl acetate, the aqueous phase is separated out and extracted twice with ethyl acetate, and the combined organic phases are washed with saturated aqueous ammonium chloride solution and dried over sodium sulfate. After evaporating off the solvent, the residue obtained is purified by chromatography on a column of silica gel, eluting with a 99/1 mixture of dichloromethane and methanol, and 0.07 g of pure product is thus obtained in the form of a white powder. m.p. ( C.): 132-134 C., LC-MS: M+H=491, 1H NMR (DMSO) delta (ppm): 8.05 (d, 1H); 7.90-7.70 (m, 2H); 7.60-7.50 (m, 2H); 7.35 (d, 1H); 6.90 (s, 1H); 5.25 (m, 2H); 4.45-4.30 (m, 4H); 3.40-3.20 (m, 4H); 1.90-1.60 (m, 4H); 1.35 (t, 3H).

Reference： [1]Patent: US2012/15950,2012,A1 .Location in patent: Page/Page column 17

45
[ 1810-72-6 ]
[ 1268713-20-7 ]
[ 1395033-77-8 ]

Yield	Reaction Conditions	Operation in experiment
10%	With caesium carbonate;copper(I) oxide; 8-quinolinol; In dimethyl sulfoxide; at 170℃; for 1h;microwave irradiation;	A mixture of ethyl l-(5,6-dimethyl-lH-benzo[<i]imidazol-2-yl)piperidine-4-carboxylate (90 mg, 0.30 mmol), dimethyl sulfoxide (0.7 mL), caesium carbonate (136 mg, 0.42 mmol), 2,6- dichloroquinoline (177 mg, 0.90 mmol), 8-hydroxyquinoline (8.7 mg, 0.060 mmol),polyethylene glycol 400 (60 mg, 0.15 mmol) and copper(I) oxide (8.5 mg, 0.060 mmol) was subjected to microwave conditions for one hour at 170 C. The reaction mixture was diluted with N,N-dimethylformamide (5 mL), filtered and concentrated in vacuo. The residue was purified by silica flash chromatography (20-50% ethyl acetate in isohexane) to give 14.1 mg (10% yield) of ethyl l-(l-(6-chloroquinolin-2-yl)-5,6-dimethyl-lH-benzo[<i]imidazol-2-yl)piperidine-4- carboxylate as a white solid. LC-MS (m/z) 463.2 (M+l).

Reference： [1]Patent: WO2012/117062,2012,A1 .Location in patent: Page/Page column 39

46
[ 1810-72-6 ]
[ 1268712-98-6 ]
[ 1395033-71-2 ]

Yield	Reaction Conditions	Operation in experiment
14%	With caesium carbonate;copper(I) oxide; 8-quinolinol; In dimethyl sulfoxide; at 170℃; for 1h;microwave irradiation;	A mixture of ethyl l-(5,6-dichloro-lH-benzo[<i]imidazol-2-yl)piperidine-4-carboxylate (100 mg, 0.29 mmol), dimethylsulfoxide (0.7 mL), caesium carbonate (133 mg, 0.41 mmol), 2,6- dichloroquinoline (174 mg, 0.89 mmol), 8-hydroxyquinoline (8.5 mg, 0.058 mmol),polyethylene glycol 400 (58 mg, 0.15 mmol) and copper(I) oxide (8.4 mg, 0.058 mmol) was subjected to microwave conditions for one hour at 170 C. The reaction mixture was diluted with N,N-dimethylformamide (5 mL), filtered and concentrated in vacuo. The residue was purified by silica flash chromatography (10-50%) ethyl acetate in isohexane) to give 21.1 mg (14% yield) of ethyl l-(5,6-dichloro-l-(6-chloroquinolin-2-yl)-lH-benzo[<i]imidazol-2-yl)piperidine-4- carboxylate as a white solid. LC-MS (m/z) 505.1 (M+l).

Reference： [1]Patent: WO2012/117062,2012,A1 .Location in patent: Page/Page column 35

47
[ 1810-72-6 ]
[ 57260-71-6 ]
[ 890709-18-9 ]

Yield	Reaction Conditions	Operation in experiment
61%	With potassium carbonate; In N,N-dimethyl-formamide; at 140℃; for 4h;	[0456] To a solution of <strong>[1810-72-6]2,6-dichloroquinoline</strong> (1.5 g, 7.6 mmol) in DMF (50 ml) was added tert-butyl piperazine-1-carboxylate (7.1 g, 38.1 mmol, 5 eq), and potassium carbonate (2.1 g, 15.1 mmol, 2 eq). The mixture was stirred for 4 hours at 140 C. and then quenched by the addition of water (300 ml) and then extracted with ethyl acetate (3×100 ml). The organic layers were combined, washed with saturated aqueous sodium chloride (3×300 ml), dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to give a residue. The crude material was purified by silica gel chromatography using 1-10% ethyl acetate in petroleum ether to elute. The product-containing fractions were combined and concentrated under vacuum to afford tert-butyl 4-(6-chloroquinolin-2-yl)piperazine-1-carboxylate as a light yellow solid (1.6 g, 61%). (ES, m/z): [M+H]+ 348; 1H NMR (300 MHz, DMSO): delta 8.03 (d, J=9.3 Hz, 1H), 7.81 (d, J=2.1 Hz, 1H), 7.50-7.58 (m, 2H), 7.29 (d, J=9.3 Hz, 1H), 3.68-3.71 (t, J=5.1 Hz, 4H), 3.43-3.47 (t, J=4.5 Hz, 4H), 1.43 (s, 9H).

Reference： [1]Patent: US2014/142114,2014,A1 .Location in patent: Paragraph 0455; 0456

48
[ 1810-72-6 ]
1-[4-(6-chloroquinolin-2-yl)piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]ethan-1-one [ No CAS ]

Reference： [1]Patent: US2014/142114,2014,A1

49
[ 1810-72-6 ]
[ 1557967-47-1 ]

Reference： [1]Medicinal Chemistry Research,2014,vol. 23,p. 3468 - 3477

50
[ 1810-72-6 ]
[ 1557967-34-6 ]

Reference： [1]Medicinal Chemistry Research,2014,vol. 23,p. 3468 - 3477

51
[ 1810-72-6 ]
[ 630-10-4 ]
C₁₀H₈ClN₃Se*ClH [ No CAS ]

Reference： [1]Medicinal Chemistry Research,2014,vol. 23,p. 3468 - 3477

52
[ 1810-72-6 ]
[ 106-96-7 ]
[ 1557967-62-0 ]

Reference： [1]Medicinal Chemistry Research,2014,vol. 23,p. 3468 - 3477

53
[ 1810-72-6 ]
2-amino-6-chloroquinoline-8-sulfonyl chloride [ No CAS ]

Reference： [1]Patent: WO2014/139144,2014,A1
[2]Patent: US2014/288081,2014,A1

54
[ 1810-72-6 ]
4-(2-amino-6-chloroquinoline-8-sulfonamido)benzoic acid [ No CAS ]

Reference： [1]Patent: WO2014/139144,2014,A1
[2]Patent: US2014/288081,2014,A1

55
[ 1810-72-6 ]
4-(2-aminoquinoline-8-sulfonamido)benzoic acid [ No CAS ]

Reference： [1]Patent: WO2014/139144,2014,A1
[2]Patent: US2014/288081,2014,A1

56
[ 1810-72-6 ]
2-amino-N-(4-(4-hydroxy-4-isobutylpiperidine-1-carbonyl)phenyl)quinoline-8-sulfonamide [ No CAS ]

Reference： [1]Patent: WO2014/139144,2014,A1
[2]Patent: US2014/288081,2014,A1

57
[ 6563-10-6 ]
[ 1810-72-6 ]

Yield	Reaction Conditions	Operation in experiment
71%	With trichlorophosphate; In dichloromethane; N,N-dimethyl-formamide; at 0 - 25℃;Inert atmosphere;	General procedure: To a stirred solution of the appropriate azine N-oxides in anhydrous CH2Cl2 (0.1M) at 0 C is added POCl3 (1.2 equiv) followed by dropwise addition of DMF (0.5 equiv) under argon. The resulting reaction mixture was warmed to 25 C and stirred for several hours until the reaction is complete as indicated by TLC. Saturated aqueous sodium carbonate solution is added to the reaction mixture slowly to adjust the pH to 7~8. The resulting mixture is separated and the aqueous phase is extracted with CH2Cl2 thoroughly. The organic phase is combined and washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to afford the crude product, which is purified by flash column chromatography using PE/EA (80:1) as eluent.

Reference： [1]European Journal of Organic Chemistry,2016,vol. 2016,p. 1606 - 1611
[2]Tetrahedron Letters,2014,vol. 55,p. 7130 - 7132

58
[ 1810-72-6 ]
[ 17680-04-5 ]
[ 1075185-80-6 ]

Reference： [1]Chemistry - A European Journal,2015,vol. 21,p. 1961 - 1965

59
[ 1810-72-6 ]
[ 7353-91-5 ]
[ 107274-76-0 ]

Reference： [1]Chemistry - A European Journal,2015,vol. 21,p. 1961 - 1965

60
[ 1810-72-6 ]
C₇H₃BrClF₃Mg [ No CAS ]
6-chloro-2-(4-chloro-3-(trifluoromethyl)phenyl)quinoline [ No CAS ]

Reference： [1]Chemistry - A European Journal,2015,vol. 21,p. 1961 - 1965

61
[ 1810-72-6 ]
4-fluoro-phenylmagnesium bromide lithium chloride [ No CAS ]
6-chloro-2-(4-fluorophenyl)quinoline [ No CAS ]

Reference： [1]Chemistry - A European Journal,2015,vol. 21,p. 8242 - 8249

62
[ 1810-72-6 ]
[4-(trifluoromethyl)phenyl]magnesium bromide lithium chloride [ No CAS ]
6-chloro-2-(4-(trifluoromethyl)phenyl)quinoline [ No CAS ]

Reference： [1]Chemistry - A European Journal,2015,vol. 21,p. 8242 - 8249

63
[ 1810-72-6 ]
C₂₅H₂₃ClN₂O₂ [ No CAS ]