Name: 13669-65-3|3-Bromo-6-chloroquinoline|98%
Brand: Ambeed
SKU: A542339
Rating: 95 (32 reviews)

1
6-chloro-quinoline; perbromide [ No CAS ]
[ 13669-65-3 ]

Yield	Reaction Conditions	Operation in experiment
	at 180 - 190℃;

Reference： [1]Claus; Howitz [Journal fur praktische Chemie (Leipzig 1954), 1894, vol. <2> 50, p. 239] Claus; Schedler [Journal fur praktische Chemie (Leipzig 1954), 1894, vol. <2> 49, p. 365] Claus; Caroselli [Journal fur praktische Chemie (Leipzig 1954), 1895, vol. <2> 51, p. 484]

Yield	Reaction Conditions	Operation in experiment
	at 180 - 190℃;

3
[ 612-57-7 ]
[ 13669-65-3 ]

Yield	Reaction Conditions	Operation in experiment
61%	With N-Bromosuccinimide; In acetic acid; at 70 - 115℃; for 3.5h;	A slurry of of <strong>[612-57-7]6-chloroquinoline</strong> (50 g, 306 mmol) and NBS (59.8 g, 336 mmol) inAcOH (500 ml.) was heated at 1 15 C for 90 min, then was allowed to cool to roomtemperature. More NBS (0.25 eq. 15 g) was added and the reaction mixture was heated at 70 C for 2 h. The resulting mixture was allowed to cool to room temperature and wasconcentrated. The residue was taken up into water (500 ml_). The resulting slurry was filtered, solid washed with water. The solid was dissolved in CH2CI2 (500 ml_). The layers were separated. The organic layer was concentrated and purified by multiple column chromatography (0-40% CH2CI2/hexane) and triturations using CH2CI2 to obtain 3-bromo-<strong>[612-57-7]6-chloroquinoline</strong> (45.2 g, 61 .0 % yield) as an off-white solid: 1 H NMR (400 MHz, DMSO-d6) delta ppm 7.80 (dd, 1 H) 8.03 (d, J=9.07 Hz, 1 H) 8.08 (d, J=2.34 Hz, 1 H) 8.69 (d, J=2.24 Hz, 1 H) 8.96 (d, J=2.24 Hz, 1 H); ES LC-MS m/z =242.1 (Br79, CI35 M+H)+.
	With N-Bromosuccinimide; In dichloromethane; cyclohexane; water; acetic acid;	4.1 3-Bromo-<strong>[612-57-7]6-chloroquinoline</strong>. 4.8 g (29 mmol) of <strong>[612-57-7]6-chloroquinoline</strong>, in solution in 50 ml of acetic acid, are introduced into a 100 ml three-necked round-bottomed flask, after which 5.75 g (32 mmol) of N-bromosuccinimide are added and the mixture is heated at 100 C. for 6 h. The reaction mixture is poured into 100 ml of water and the whole is extracted with dichloromethane. The pooled organic phases are dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography on a silica gel column, with the elution being carried out using a 50/50, and then a 30/70, mixture of cyclohexane and dichloromethane. 4.86 g of product are obtained. Melting point: 110-111 C.
		The synthesis was done by the same procedure as that of J. J. Eisch (J. Org. Chem. Vol. 27, p.1318, 1962). Bromine (79 mul) and carbon tetrachloride (2 ml) were added to <strong>[612-57-7]6-chloroquinoline</strong> (250 mg) and stirred at 90C for two hours. Pyridine (123 mul) was added to the reaction solution and stirred at the same temperature for 16 hours. The reaction solution was concentrated and purified with a silica gel chromatography (hexane - ethyl acetate) to obtain the title compound (250 mg).

Reference： [1]Patent: WO2012/37108,2012,A1 .Location in patent: Page/Page column 118
[2]Patent: US2003/119840,2003,A1
[3]Patent: EP1454898,2004,A1 .Location in patent: Page 57; 58

4
[ 13669-65-3 ]
[ 283-38-5 ]
[ 352203-38-4 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonia; caesium carbonate In tetrahydrofuran; methanol; dichloromethane	4 4.2 4-(6-Chloroquinolin-3-yl)-1,4-diazabicyclo[3.2.2]_nonane 4.2 4-(6-Chloroquinolin-3-yl)-1,4-diazabicyclo[3.2.2]_nonane 0.53 g (2.18 mmol) of 3-bromo-6-chloro_quinoline, 0.25 g (2 mmol) of 1,4-diazabicyclo[3.2.2]_nonane, 0.018 g (0.08 mmol) of palladium diacetate, 0.91 g (2.8 mmol) of cesium carbonate and 0.05 g (0.08 mmol) of 2,2'-bis(diphenylphosphino)-1,1'-bi_naphthyl, in 15 ml of tetrahydrofuran, are introduced consecutively into a 50 ml three-necked round-bottomed flask and the reaction mixture is heated at reflux for 26 h. The inorganic products are separated off by filtration and the solvent is evaporated under reduced pressure; the residue is then purified by chromatography on a silica gel column, with the elution being carried out using a 95/5/0.5, and then a 90/10/1, mixture of dichloromethane, methanol and ammonia. 0.40 g of solid is obtained, with this solid being recrystallized in diisopropyl ether. Melting point: 134-135° C.

Reference： [1]Current Patent Assignee: SANOFI - US2003/119840, 2003, A1

5
[ 13669-65-3 ]
[ 1059063-34-1 ]
[ 1059063-66-9 ]

Yield	Reaction Conditions	Operation in experiment
	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; sodium t-butanolate In toluene at 100℃;

Reference： [1]Location in patent: scheme or table DiMauro, Erin F.; Buchanan, John L.; Cheng, Alan; Emkey, Renee; Hitchcock, Stephen A.; Huang, Liyue; Huang, Ming Y.; Janosky, Brett; Lee, Josie H.; Li, Xingwen; Martin, Matthew W.; Tomlinson, Susan A.; White, Ryan D.; Zheng, Xiao Mei; Patel, Vinod F.; Fremeau Jr., Robert T. [Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 15, p. 4267 - 4274]

6
[ 13669-65-3 ]
[ 1366129-06-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 2 h / 80 °C 6: potassium phosphate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 16 h / 100 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

7
[ 13669-65-3 ]
N-[5-{2-amino-3-[4-(ethylsulfonyl)phenyl]-6-quinolinyl}-2-(methyloxy)-3-pyridinyl]-2,4-difluoro-N-methylbenzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 2 h / 80 °C 6: potassium phosphate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 16 h / 100 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

8
[ 13669-65-3 ]
[ 1366129-14-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 2 h / 80 °C 6: potassium phosphate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 16 h / 100 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

9
[ 13669-65-3 ]
[ 1366129-34-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 2 h / 80 °C 6: potassium phosphate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 16 h / 100 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

10
[ 13669-65-3 ]
[ 1366129-35-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 2 h / 80 °C 6: potassium phosphate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 16 h / 100 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

11
[ 13669-65-3 ]
[ 1366129-36-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 2 h / 80 °C 6: potassium phosphate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 16 h / 100 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

12
[ 13669-65-3 ]
[ 1366129-37-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 2 h / 80 °C 6: potassium phosphate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 16 h / 100 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

13
[ 13669-65-3 ]
[ 1366129-38-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 2 h / 80 °C 6: potassium phosphate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 16 h / 100 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

14
[ 13669-65-3 ]
[ 1366129-44-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 2 h / 80 °C 6: potassium phosphate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 16 h / 100 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

15
[ 13669-65-3 ]
[ 1366129-48-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 2 h / 80 °C 6: potassium phosphate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 10 h / 100 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

16
[ 13669-65-3 ]
[ 1366129-49-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 2 h / 80 °C 6: potassium phosphate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 10 h / 100 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

17
[ 13669-65-3 ]
[ 1366129-50-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 2 h / 80 °C 6: potassium phosphate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 10 h / 100 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

18
[ 13669-65-3 ]
[ 1366129-73-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 2 h / 80 °C 6: potassium phosphate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 24 h / 100 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

19
[ 13669-65-3 ]
[ 1366129-92-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 2 h / 80 °C 6: potassium phosphate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 20 h / 100 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

20
[ 13669-65-3 ]
[ 1366129-97-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 2 h / 80 °C 6: potassium phosphate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 20 h / 100 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

21
[ 13669-65-3 ]
[ 1366129-98-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 2 h / 80 °C 6: potassium phosphate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 24 h / 100 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

22
[ 13669-65-3 ]
[ 1366132-01-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,2-dimethoxyethane; water / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

23
[ 13669-65-3 ]
[ 1366130-12-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,2-dimethoxyethane; water / 80 °C / Inert atmosphere 6: XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 100 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

24
[ 13669-65-3 ]
ethyl 2-amino-6-chloroquinoline-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene / palladium diacetate / toluene / 8 h / 90 °C / 4654.46 Torr

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

25
[ 13669-65-3 ]
[ 1366132-23-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene / palladium diacetate / toluene / 8 h / 90 °C / 4654.46 Torr 6: potassium acetate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 16 h / 100 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

26
[ 13669-65-3 ]
[ 1366131-24-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	With trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct In dichloromethane	15.2 To a pale yellow solution of 3-bromo-6-chloroquinoline (45.2 g, 186 mmol) in CH2CI2 (1500 mL) was added urea hydrogen peroxide (43.8 g, 466 mmol). To the resulting slurry was slowly added TFAA (52.7 mL, 373 mmol). Moderate exotherm was observed. Most of solids dissolved in the bright yellow solution by the end of addition. The reaction mixture was stirred overnight. The resulting mixture was quenched with a sat. Na2S203 solution (400 mL). The organic layer was washed with a sat. NaHC03 solution, dried (Na2S04) and concentrated to obtain 3-bromo-6-chloroquinoline 1-oxide (50 g, quant, yield) as a light yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 7.84 (dd, J=9.27, 2.15 Hz, 1 H) 8.19 (d, 1 H) 8.24 (s, 1 H) 8.45 (d, J=9.27 Hz, 1 H) 8.89 (s, 1 H); ES LC-MS m/z =258.1 (Br79, CI35, M+H)+.

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1 Location in patent: Page/Page column 118-119

27
[ 13669-65-3 ]
[ 1366131-25-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

28
[ 13669-65-3 ]
[ 1366131-27-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

29
[ 13669-65-3 ]
[ 1366131-26-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

30
[ 13669-65-3 ]
[ 1366129-69-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 2 h / 80 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

31
[ 13669-65-3 ]
[ 1366131-28-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 3 h / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

32
[ 13669-65-3 ]
[ 1366127-89-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 3 h / 80 °C / Inert atmosphere 6: potassium phosphate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 16 h / 100 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

33
[ 13669-65-3 ]
[ 1366131-29-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 3 h / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

34
[ 13669-65-3 ]
[ 1366127-90-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: trifluoromethylsulfonic anhydride; urea hydrogen peroxide adduct / dichloromethane 2: trichlorophosphate / 1 h / Reflux 3: N-ethyl-N,N-diisopropylamine / butan-1-ol / 40 h / 130 °C / Sealed tube 4: trifluoroacetic acid / 3 h / 65 °C 5: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,2-dimethoxyethane; water / 3 h / 80 °C / Inert atmosphere 6: potassium phosphate; XPhos / bis(dibenzylideneacetone)-palladium⁽⁰⁾ / water; butan-1-ol / 16 h / 100 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/37108, 2012, A1

35
[ 13669-65-3 ]
[ 1426231-95-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium thiomethoxide / N,N-dimethyl-formamide / 4 h / Inert atmosphere 1.2: 0 °C / Inert atmosphere 2.1: sodium hypochlorite; hydrogenchloride / chloroform / 0.5 h / 0 - 5 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0 - 20 °C

Reference： [1]Zajdel, Pawel; Marciniec, Krzysztof; Maslankiewicz, Andrzej; Grychowska, Katarzyna; Satala, Grzegorz; Duszynska, Beata; Lenda, Tomasz; Siwek, Agata; Nowak, Gabriel; Partyka, Anna; Wrobel, Dagmara; Jastrzebska-Wiesek, Magdalena; Bojarski, Andrzej J.; Wesolowska, Anna; Pawlowski, MacIej [European Journal of Medicinal Chemistry, 2013, vol. 60, p. 42 - 50]

36
[ 13669-65-3 ]
[ 1426231-99-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium thiomethoxide / N,N-dimethyl-formamide / 4 h / Inert atmosphere 1.2: 0 °C / Inert atmosphere 2.1: sodium hypochlorite; hydrogenchloride / chloroform / 0.5 h / 0 - 5 °C 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0 - 20 °C

Reference： [1]Zajdel, Pawel; Marciniec, Krzysztof; Maslankiewicz, Andrzej; Grychowska, Katarzyna; Satala, Grzegorz; Duszynska, Beata; Lenda, Tomasz; Siwek, Agata; Nowak, Gabriel; Partyka, Anna; Wrobel, Dagmara; Jastrzebska-Wiesek, Magdalena; Bojarski, Andrzej J.; Wesolowska, Anna; Pawlowski, MacIej [European Journal of Medicinal Chemistry, 2013, vol. 60, p. 42 - 50]

37
[ 13669-65-3 ]
[ 1426231-93-7 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-bromo-6-chloroquinoline With sodium thiomethoxide In N,N-dimethyl-formamide for 4h; Inert atmosphere; Stage #2: With hydrogenchloride at 0℃; Inert atmosphere;	2 4.2 Synthesis of azinesulfonyl chloride 22-28 A mixture of bromoazine (1-7) (4 mmol), sodium methanethiolate (20 mmol) and dry DMF (12 mL) was boiled with stirring under argon atmosphere for 4 h. It was then cooled to 70 °C and the volatile components were evaporated under vacuum from water bath. The remaining crude sodium azinethiolates (8-14), were cooled down on an ice-water bath (under argon atmosphere), and carefully acidified with conc. hydrochloric acid (12 mL). Then, CHCl3 (12 mL) was added and 6% aqueous solution of sodium hypochlorite (19 mL, 13.3 mmol) was dropped within 30 min to the well-stirred (cold 5 °C) mixture of hydrochloric acid solution of mercaptoazines (15-21) and CHCl3 at such a rate that temperature was maintained below 5 °C. The mixture was poured into 30 g of ice. The chloroform layer was separated, and aqueous layer was extracted with CHCl3 (3 * 10 mL). The chloroform extracts were combined, washed with water and dried over anhydrous sodium sulfate. CHCl3 was evaporated to leave solid residue. The residue was recrystallized from benzene to give chlorosulfonylazines (22-28)

Reference： [1]Zajdel, Pawel; Marciniec, Krzysztof; Maslankiewicz, Andrzej; Grychowska, Katarzyna; Satala, Grzegorz; Duszynska, Beata; Lenda, Tomasz; Siwek, Agata; Nowak, Gabriel; Partyka, Anna; Wrobel, Dagmara; Jastrzebska-Wiesek, Magdalena; Bojarski, Andrzej J.; Wesolowska, Anna; Pawlowski, MacIej [European Journal of Medicinal Chemistry, 2013, vol. 60, p. 42 - 50]

38
[ 13669-65-3 ]
[ 1360625-43-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide / 12 h / 80 °C / Inert atmosphere 2: chlorine; acetic acid / chloroform / 0.75 h / 15 - 17 °C
	Multi-step reaction with 2 steps 1.1: sodium hydroxide / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere 1.2: 6 h 2.1: hydrogenchloride; sodium hypochlorite / chloroform; water / 1 h / 5 - 10 °C

Reference： [1]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]
[2]Marciniec, Krzysztof; Pawełczak, Bartosz; Latocha, Małgorzata; Skrzypek, Leszek; Maciązek-Jurczyk, Małgorzata; Boryczka, Stanisław; Supuran, Claudiu T. [Molecules, 2017, vol. 22, # 2]

39
[ 13669-65-3 ]
6-chloro-3-quinolinesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N,N-dimethyl-formamide / 12 h / 80 °C / Inert atmosphere 2: chlorine; acetic acid / chloroform / 0.75 h / 15 - 17 °C 3: ammonium hydroxide / water / 0.5 h / 45 °C

Reference： [1]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]

40
[ 13669-65-3 ]
2Na⁽¹⁺⁾*C₉H₅NS₂^(2-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium thiomethoxide In N,N-dimethyl-formamide for 6h; Inert atmosphere;	3.4. Procedure for the Synthesis of 3,6-Di(3-propynylsulfanyl)quinoline (11) A mixture of 6-chloro-3-bromoquinoline (242 mg, 1 mmol), sodium methanethiolate (840mg, 12 mmol), and dry DMF (10 mL) was boiled with stirring under argon atmosphere for 6 h.The mixture was then cooled to room temperature and poured into cold 8% aqueous NaOH (30mL), and prpargyl bromide (0.126 mL, 195 mg, 1.65 mmol) was added dropwise with stirring. Thestirring cotinued at room temperature for 1 h. The solid was filtered off, washed with water, andair-dried. The crude product was purified by column chromatography (ethyl acetate) to give pure3,6-di(3-propynylsulfanyl)quinoline (11).

Reference： [1]Marciniec, Krzysztof; Pawełczak, Bartosz; Latocha, Małgorzata; Skrzypek, Leszek; Maciązek-Jurczyk, Małgorzata; Boryczka, Stanisław; Supuran, Claudiu T. [Molecules, 2017, vol. 22, # 2]

41
[ 13669-65-3 ]
3,6-dichlorosulfonylquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium hydroxide / dimethyl sulfoxide / 1 h / 80 °C / Inert atmosphere 1.2: 5 h / 80 °C / Inert atmosphere 2.1: sodium thiomethoxide / N,N-dimethyl-formamide / 4 h / Inert atmosphere; Reflux 2.2: Inert atmosphere 3.1: hydrogenchloride; sodium hypochlorite / water; chloroform / 5 °C
	Multi-step reaction with 3 steps 1.1: N,N-dimethyl-formamide / 4 h / 80 °C / Inert atmosphere 2.1: sodium thiomethoxide / N,N-dimethyl-formamide / 4 h / Inert atmosphere; Reflux 2.2: Inert atmosphere 3.1: hydrogenchloride; sodium hypochlorite / water; chloroform / 5 °C
	Multi-step reaction with 2 steps 1: sodium thiomethoxide / N,N-dimethyl-formamide / 6 h / Inert atmosphere 2: hydrogenchloride; sodium hypochlorite / water / 0.75 h / 20 °C

Reference： [1]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]
[2]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]
[3]Marciniec, Krzysztof; Pawełczak, Bartosz; Latocha, Małgorzata; Skrzypek, Leszek; Maciązek-Jurczyk, Małgorzata; Boryczka, Stanisław; Supuran, Claudiu T. [Molecules, 2017, vol. 22, # 2]

42
[ 13669-65-3 ]
3,6-di(N,N-dimethylsulfamoyl)quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium thiomethoxide / N,N-dimethyl-formamide / 4 h / Inert atmosphere; Reflux 1.2: Inert atmosphere 2.1: hydrogenchloride; sodium hypochlorite / water; chloroform / 5 °C 3.1: water / 0.5 h / 45 °C
	Multi-step reaction with 4 steps 1.1: sodium hydroxide / dimethyl sulfoxide / 1 h / 80 °C / Inert atmosphere 1.2: 5 h / 80 °C / Inert atmosphere 2.1: sodium thiomethoxide / N,N-dimethyl-formamide / 4 h / Inert atmosphere; Reflux 2.2: Inert atmosphere 3.1: hydrogenchloride; sodium hypochlorite / water; chloroform / 5 °C 4.1: water / 0.5 h / 45 °C
	Multi-step reaction with 4 steps 1.1: N,N-dimethyl-formamide / 4 h / 80 °C / Inert atmosphere 2.1: sodium thiomethoxide / N,N-dimethyl-formamide / 4 h / Inert atmosphere; Reflux 2.2: Inert atmosphere 3.1: hydrogenchloride; sodium hypochlorite / water; chloroform / 5 °C 4.1: water / 0.5 h / 45 °C

Reference： [1]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]
[2]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]
[3]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]

43
[ 13669-65-3 ]
3,6-di(N-tert-butylsulfamoyl)quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium thiomethoxide / N,N-dimethyl-formamide / 4 h / Inert atmosphere; Reflux 1.2: Inert atmosphere 2.1: hydrogenchloride; sodium hypochlorite / water; chloroform / 5 °C 3.1: chloroform / 0.75 h / 0 - 5 °C
	Multi-step reaction with 4 steps 1.1: sodium hydroxide / dimethyl sulfoxide / 1 h / 80 °C / Inert atmosphere 1.2: 5 h / 80 °C / Inert atmosphere 2.1: sodium thiomethoxide / N,N-dimethyl-formamide / 4 h / Inert atmosphere; Reflux 2.2: Inert atmosphere 3.1: hydrogenchloride; sodium hypochlorite / water; chloroform / 5 °C 4.1: chloroform / 0.75 h / 0 - 5 °C
	Multi-step reaction with 4 steps 1.1: N,N-dimethyl-formamide / 4 h / 80 °C / Inert atmosphere 2.1: sodium thiomethoxide / N,N-dimethyl-formamide / 4 h / Inert atmosphere; Reflux 2.2: Inert atmosphere 3.1: hydrogenchloride; sodium hypochlorite / water; chloroform / 5 °C 4.1: chloroform / 0.75 h / 0 - 5 °C

Reference： [1]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]
[2]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]
[3]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]

44
[ 13669-65-3 ]
quinoline-3,6-disulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: sodium thiomethoxide / N,N-dimethyl-formamide / 4 h / Inert atmosphere; Reflux 1.2: Inert atmosphere 2.1: hydrogenchloride; sodium hypochlorite / water; chloroform / 5 °C 3.1: chloroform / 0.75 h / 0 - 5 °C 4.1: boron trichloride / dichloromethane / 0.5 h / 20 °C / Inert atmosphere
	Multi-step reaction with 5 steps 1.1: sodium hydroxide / dimethyl sulfoxide / 1 h / 80 °C / Inert atmosphere 1.2: 5 h / 80 °C / Inert atmosphere 2.1: sodium thiomethoxide / N,N-dimethyl-formamide / 4 h / Inert atmosphere; Reflux 2.2: Inert atmosphere 3.1: hydrogenchloride; sodium hypochlorite / water; chloroform / 5 °C 4.1: chloroform / 0.75 h / 0 - 5 °C 5.1: boron trichloride / dichloromethane / 0.5 h / 20 °C / Inert atmosphere
	Multi-step reaction with 5 steps 1.1: N,N-dimethyl-formamide / 4 h / 80 °C / Inert atmosphere 2.1: sodium thiomethoxide / N,N-dimethyl-formamide / 4 h / Inert atmosphere; Reflux 2.2: Inert atmosphere 3.1: hydrogenchloride; sodium hypochlorite / water; chloroform / 5 °C 4.1: chloroform / 0.75 h / 0 - 5 °C 5.1: boron trichloride / dichloromethane / 0.5 h / 20 °C / Inert atmosphere

Reference： [1]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]
[2]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]
[3]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]

45
[ 13669-65-3 ]
[ 5188-07-8 ]
6-chloro-3-methylsulfanylquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	In N,N-dimethyl-formamide at 80℃; for 4h; Inert atmosphere; regioselective reaction;

Reference： [1]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]

46
[ 13669-65-3 ]
[ 3492-64-6 ]
6-chloro-3-phenylmethylsulfanylquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	In N,N-dimethyl-formamide at 80℃; for 12h; Inert atmosphere; regioselective reaction;

Reference： [1]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]

47
[ 13669-65-3 ]
[ 867-44-7 ]
6-chloro-3-methylsulfanylquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	Stage #1: S-Methylisothiourea sulfate With sodium hydroxide In dimethyl sulfoxide at 80℃; for 1h; Inert atmosphere; Stage #2: 3-bromo-6-chloroquinoline In dimethyl sulfoxide at 80℃; for 5h; Inert atmosphere;

Reference： [1]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]

48
[ 13669-65-3 ]
3,6-dimercaptoquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-bromo-6-chloroquinoline With sodium thiomethoxide In N,N-dimethyl-formamide for 4h; Inert atmosphere; Reflux; Stage #2: With hydrogenchloride In water Inert atmosphere;
	Multi-step reaction with 2 steps 1.1: sodium hydroxide / dimethyl sulfoxide / 1 h / 80 °C / Inert atmosphere 1.2: 5 h / 80 °C / Inert atmosphere 2.1: sodium thiomethoxide / N,N-dimethyl-formamide / 4 h / Inert atmosphere; Reflux 2.2: Inert atmosphere
	Multi-step reaction with 2 steps 1.1: N,N-dimethyl-formamide / 4 h / 80 °C / Inert atmosphere 2.1: sodium thiomethoxide / N,N-dimethyl-formamide / 4 h / Inert atmosphere; Reflux 2.2: Inert atmosphere

Reference： [1]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]
[2]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]
[3]Marciniec, Krzysztof; Maslankiewicz, Andrzej; Maslankiewicz, Maria J. [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1019 - 1025]

49
[ 13669-65-3 ]
3,6-di(3-propynylsulfanyl)quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium thiomethoxide / N,N-dimethyl-formamide / 6 h / Inert atmosphere 2: sodium hydroxide / water / 1 h / 20 °C

Reference： [1]Marciniec, Krzysztof; Pawełczak, Bartosz; Latocha, Małgorzata; Skrzypek, Leszek; Maciązek-Jurczyk, Małgorzata; Boryczka, Stanisław; Supuran, Claudiu T. [Molecules, 2017, vol. 22, # 2]

50
[ 13669-65-3 ]
3,6-Di[N-methyl-N-(3-propynyl)sulfamoyl]quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: sodium thiomethoxide / N,N-dimethyl-formamide / 6 h / Inert atmosphere 2: hydrogenchloride; sodium hypochlorite / water / 0.75 h / 20 °C 3: triethylamine / chloroform / 5 h / 0 - 5 °C

Reference： [1]Marciniec, Krzysztof; Pawełczak, Bartosz; Latocha, Małgorzata; Skrzypek, Leszek; Maciązek-Jurczyk, Małgorzata; Boryczka, Stanisław; Supuran, Claudiu T. [Molecules, 2017, vol. 22, # 2]

51
[ 13669-65-3 ]
6-Chloro-3-[N-methyl-N-(3-propynyl)sulfamoyl]quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium hydroxide / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere 1.2: 6 h 2.1: hydrogenchloride; sodium hypochlorite / chloroform; water / 1 h / 5 - 10 °C 3.1: triethylamine / chloroform / 3 h / 0 - 5 °C

Reference： [1]Marciniec, Krzysztof; Pawełczak, Bartosz; Latocha, Małgorzata; Skrzypek, Leszek; Maciązek-Jurczyk, Małgorzata; Boryczka, Stanisław; Supuran, Claudiu T. [Molecules, 2017, vol. 22, # 2]

52
[ 13669-65-3 ]
[ 538-28-3 ]
6-chloro-3-phenylmethylsulfanylquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%		A mixture of S-benzyl-isothiouronium chloride (305 mg, 1.5mmol), NaOH (200 mg, 5 mmol),and dry DMF (10 mL) was heated with stirring at 80 C under an argon atmosphere for 1 h. Then,6-chloro-3-bromoquinoline (7) (242 mg, 1 mmol) was added, and heating and stirring continued for 6 h.The mixture was cooled to room temperature and poured into ice water (80 mL). The solid was filteredoff, washed with water, and air-dried. 6-Chloro-3-phenylmethyl-sulfanylquinoline was recrystallizedfrom a mixture of hexane?CH2Cl2 (7:3, v/v) to give pure compound (10) (89percent). m.p. 77?78 °C (lit. m.p.77?78 °C [34]).

Reference： [1]Molecules,2017,vol. 22

53
[ 13669-65-3 ]
6-(3-morpholinoquinolin-6-yl)-5-phenyl-1,2,4-triazin-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; caesium carbonate / tetrahydrofuran / 70 °C / Inert atmosphere 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / 1,4-dioxane; water / 2 h / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: JIANGSU HENGRUI MEDICINE CO., LTD. - EP3569596, 2019, A1

54
[ 110-91-8 ]
[ 13669-65-3 ]
4-(6-chloroquinolin-3-yl)morpholine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66.2%	With palladium diacetate; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In tetrahydrofuran at 70℃; Inert atmosphere;	39.1 4-(6-Chloroquinolin-3-yl)morpholine 39b 3-Bromo-6-chloroquinoline 39a (266 mg, 1.1 mmol, prepared according to the known method disclosed in "Journal of Heterocyclic Chemistry, 2015, 52(4), 1019-1025"), morpholine (87 mg, 1 mmol), palladium acetate (12 mg, 0.05 mmol), (±)-2,2'-bis-(diphenylphosphino)-1,1'-binaphthalene (31 mg, 0.05 mmol) and cesium carbonate (652 mg, 2 mmol) were dissolved in 10 mL of tetrahydrofuran under an argon atmosphere. The reaction solution was heated to 70°C, and stirred overnight. The reaction was stopped, and the reaction solution was cooled to room temperature and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by CombiFlash rapid preparation instrument with elution system A to obtain the title product 39b (180 mg), yield: 66.2%. MS m/z (ESI): 249.7 [M+1].

Reference： [1]Current Patent Assignee: JIANGSU HENGRUI MEDICINE CO., LTD. - EP3569596, 2019, A1 Location in patent: Paragraph 0241; 0242

55
[ 13669-65-3 ]
[ 3406-77-7 ]
6-chloro-3-((4-methoxyphenyl)thio)quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With tetraaqua[4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]nickel(II) chloride; (Ir[dF(Me)ppy]₂(dtbbpy))PF₆; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; for 15h; Irradiation;

Reference： [1]Christian, Alec H. [Journal of Organic Chemistry, 2021, vol. 86, # 15, p. 10914 - 10920]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	13669-65-3	MDL No. :	MFCD18253965
Formula :	C₉H₅BrClN	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VIPZVVMRXUNRAT-UHFFFAOYSA-N
M.W :	242.50	Pubchem ID :	15378465
Synonyms :

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 :	54.45
TPSA :	12.89 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.18 cm/s

Log Po/w (iLOGP) :	2.4
Log Po/w (XLOGP3) :	3.66
Log Po/w (WLOGP) :	3.65
Log Po/w (MLOGP) :	3.12
Log Po/w (SILICOS-IT) :	3.76
Consensus Log Po/w :	3.32

[ CAS No. 13669-65-3 ] {[proInfo.proName]}

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Water Solubility

Medicinal Chemistry

Safety of [ 13669-65-3 ]

Application In Synthesis of [ 13669-65-3 ]

[ 13669-65-3 ] Synthesis Path-Downstream 1~55

Related Functional Groups of
[ 13669-65-3 ]

Bromides

Chlorides

Related Parent Nucleus of
[ 13669-65-3 ]

Quinolines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-4.27
Solubility :	0.0131 mg/ml ; 0.0000542 mol/l
Class :	Moderately soluble
Log S (Ali) :	-3.62
Solubility :	0.0582 mg/ml ; 0.00024 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-5.17
Solubility :	0.00162 mg/ml ; 0.00000668 mol/l
Class :	Moderately soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	1.44

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:

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

[ CAS No. 13669-65-3 ] {[proInfo.proName]}

Quality Control of [ 13669-65-3 ]

Related Doc. of [ 13669-65-3 ]

Product Details of [ 13669-65-3 ]

Calculated chemistry of [ 13669-65-3 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 13669-65-3 ]

Application In Synthesis of [ 13669-65-3 ]

[ 13669-65-3 ] Synthesis Path-Downstream 1~55

Related Functional Groups of [ 13669-65-3 ]

Bromides

Chlorides

Related Parent Nucleus of [ 13669-65-3 ]

Quinolines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 13669-65-3 ]

Related Parent Nucleus of
[ 13669-65-3 ]