Cesium carbonate → HCID 178519529, compound

HRID 1778233Notes

Reaction equation

HRID 1778233 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](=[CH:17][CH:18]=2)[N:15]=[C:14]([OH:19])[CH:13]=[C:12]3Br)=[CH:4][CH:3]=1.Cl.[C:29]([N:37]1[CH2:42][CH2:41][CH:40]([NH2:43])[CH2:39][CH2:38]1)(=[O:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC([O-])(C)C.[K+]>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].O1CCOCC1>[C:29]([N:37]1[CH2:42][CH2:41][CH:40]([NH:43][C:12]2[C:11]3[C:16](=[CH:17][CH:18]=[C:9]([CH:8]([C:21]4[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=4)[C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)[CH:10]=3)[N:15]=[C:14]([OH:19])[CH:13]=2)[CH2:39][CH2:38]1)(=[O:36])[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 162688124-AMino-1-benzoylpiperidine HClHCID 23665647Potassium tert-butoxideHCID 178515443HCID 178515443, compound

Product 1

HCID 178519529HCID 178519529, compound

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Into a 8-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 6-[bis(4-chlorophenyl)methyl]-4-bromoquinolin-2-ol (150 mg, 0.33 mmol, 1.00 equip), 1-benzoylpiperidin-4-amine hydrochloride (118 mg, 0.49 mmol, 1.50 equip), Pd2(dba)3 (30.0 mg, 0.03 mmol, 0.10 equip), dppf (63.4 mg, 0.11 mmol, 0.35 equip), Cs2CO3 (266 mg, 0.82 mmol, 2.50 equip), KOt-Bu (73 mg, 0.65 mmol, 2.00 equip), and 1,4-dioxane (3 mL). The resulting solution was stirred overnight at 100° C. The reaction was then quenched by the addition of water (100 mL). The resulting solution was extracted with ethyl acetate (3×50 mL) and the organic layers combined and dried over anhydrous sodium sulfate. The solids were removed by filtration. The filtrate was concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (20:1). The resulting residue was recrystallized from ethyl acetate:petroleum ether in the ratio of 1:10 to yield 4-[(1-benzoylpiperidin-4-yl)amino]-6-[bis(4-chlorophenyl)methyl]quinolin-2-ol as an off-white solid.

Workup

  1. customInto a 8-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. customThe reaction was then quenched by the addition of water (100 mL)
  4. extractionThe resulting solution was extracted with ethyl acetate (3×50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solids were removed by filtration
  7. concentrationThe filtrate was concentrated under vacuum
  8. customThe resulting residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-9f574a8b044b4c35889620f8bf1097aa
Source dataset
uspto-grants-2016_02
Patent number
US09266835B2

Reaction notes

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