Cesium carbonate → 6-(bis(4-chlorophenyl)methyl)-8-bromo-N-(1-((trifluoromethyl)sulfonyl)piperidin-4-yl)quinolin-4-amine

HRID 1778267Notes

Reaction equation

HRID 1778267 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)[C:9]2[CH:10]=[C:11]3[C:16](=[C:17]([Br:19])[CH:18]=2)[N:15]=[CH:14][CH:13]=[C:12]3Br)=[CH:4][CH:3]=1.[F:28][C:29]([F:41])([F:40])[S:30]([N:33]1[CH2:38][CH2:37][CH:36]([NH2:39])[CH2:35][CH2:34]1)(=[O:32])=[O:31].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:27][C:24]1[CH:23]=[CH:22][C:21]([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)[N:15]=[CH:14][CH:13]=[C:12]3[NH:39][CH:36]2[CH2:37][CH2:38][N:33]([S:30]([C:29]([F:40])([F:41])[F:28])(=[O:32])=[O:31])[CH2:34][CH2:35]2)=[CH:26][CH:25]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 435564001-Trifluoromethanesulfonylpiperidin-4-amineHCID 1183239396-(Bis(4-chlorophenyl)methyl)-4,8-dibromoquinoline

Product 1

HCID 1183240536-(bis(4-chlorophenyl)methyl)-8-bromo-N-(1-((trifluoromethyl)sulfonyl)piperidin-4-yl)quinolin-4-amine

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-dibromoquinoline (40 mg, 0.0766 mmol), 1-((trifluoromethyl)sulfonyl)piperidin-4-amine (22.6 mg, 0.0843 mmol), Pd2(dba)3 (3.5 mg, 0.00383 mmol), dppf (7.2 mg, 0.013 mmol), Cs2CO3 (62.4 mg, 0.192 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 (45% EtOAc/hexanes) chromatography to yield 6-(bis(4-chlorophenyl)methyl)-8-bromo-N-(1-((trifluoromethyl)sulfonyl)piperidin-4-yl)quinolin-4-amine.

Workup

  1. extractionThe aqueous layer was extracted with EtOAc
  2. concentrationThe combined organics were concentrated
  3. custompurified by silica column (45% EtOAc/hexanes) chromatography

Sources & evidence

ORD record
ord-9887bfaedfbf4126a43e187c0ded9188
Source dataset
uspto-grants-2016_02
Patent number
US09266835B2

Reaction notes

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