Cesium carbonate → 6-(bis(4-chlorophenyl)methyl)-8-bromo-4-((1-((trifluoromethyl)sulfonyl)piperidin-4-yl)amino)quinolin-2(1H)-one

HRID 1778268Notes

Reaction equation

HRID 1778268 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=2)[C:9]2[CH:10]=[C:11]3[C:16](=[C:17]([Br:19])[CH:18]=2)[NH:15][C:14](=[O:20])[CH:13]=[C:12]3Br)=[CH:4][CH:3]=1.[F:29][C:30]([F:42])([F:41])[S:31]([N:34]1[CH2:39][CH2:38][CH:37]([NH2:40])[CH2:36][CH2:35]1)(=[O:33])=[O:32].C([O-])([O-])=O.[Cs+].[Cs+].O1CCOCC1>CCOC(C)=O.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[Cl:28][C:25]1[CH:26]=[CH:27][C:22]([CH:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[C:9]2[CH:10]=[C:11]3[C:16](=[C:17]([Br:19])[CH:18]=2)[NH:15][C:14](=[O:20])[CH:13]=[C:12]3[NH:40][CH:37]2[CH2:38][CH2:39][N:34]([S:31]([C:30]([F:41])([F:42])[F:29])(=[O:33])=[O:32])[CH2:35][CH2:36]2)=[CH:23][CH:24]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 435564001-Trifluoromethanesulfonylpiperidin-4-amineHCID 1183239886-[Bis(4-chlorophenyl)methyl]-4,8-dibromoquinolin-2-ol

Product 1

HCID 1183240976-(bis(4-chlorophenyl)methyl)-8-bromo-4-((1-((trifluoromethyl)sulfonyl)piperidin-4-yl)amino)quinolin-2(1H)-one

Reagents, catalysts & solvents 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 6-(bis(4-chlorophenyl)methyl)-4,8-dibromoquinolin-2(1H)-one (48 mg, 0.0892 mmol), 1-((trifluoromethyl)sulfonyl)piperidin-4-amine (26.4 mg, 0.0981 mmol), Pd2(dba)3 (8.2 mg, 0.00892 mmol), dppf (14.8 mg, 0.0268 mmol), Cs2CO3 (72.7 mg, 0.223 mmol) and 1,4-dioxane (0.9 mL) was heated under argon to 95° C. overnight. The reaction was diluted with EtOAc and water. The aqueous layer was extracted with EtOAc. The combined organics were concentrated and purified by silica column (40-50% EtOAc/hexanes) chromatography to yield 6-(bis(4-chlorophenyl)methyl)-8-bromo-4-((1-((trifluoromethyl)sulfonyl)piperidin-4-yl)amino)quinolin-2(1H)-one.

Workup

  1. extractionThe aqueous layer was extracted with EtOAc
  2. concentrationThe combined organics were concentrated
  3. custompurified by silica column (40-50% EtOAc/hexanes) chromatography

Sources & evidence

ORD record
ord-140c0241f92b4c53ab264fe19dab4743
Source dataset
uspto-grants-2016_02
Patent number
US09266835B2

Reaction notes

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