Cesium carbonate → Methyl 3-(2-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)quinoline-4-carboxamido)-2,4-dimethylbenzoate

HRID 1427134Notes

Reaction equation

HRID 1427134 reaction equation
Cl[C:2]1[CH:11]=[C:10]([C:12]([NH:14][C:15]2[C:16]([CH3:26])=[C:17]([CH:22]=[CH:23][C:24]=2[CH3:25])[C:18]([O:20][CH3:21])=[O:19])=[O:13])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[C:27]([Si:31]([CH3:40])([CH3:39])[O:32][CH:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1)([CH3:30])([CH3:29])[CH3:28].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>[Si:31]([O:32][CH:33]1[CH2:34][CH2:35][N:36]([C:2]2[CH:11]=[C:10]([C:12]([NH:14][C:15]3[C:16]([CH3:26])=[C:17]([CH:22]=[CH:23][C:24]=3[CH3:25])[C:18]([O:20][CH3:21])=[O:19])=[O:13])[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=2)[CH2:37][CH2:38]1)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:40])[CH3:39]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 114813284-((Tert-butyldimethylsilyl)oxy)piperidineHCID 86707367Methyl 3-[(2-chloroquinoline-4-carbonyl)amino]-2,4-dimethyl-benzoate

Product 1

HCID 86707368Methyl 3-(2-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)quinoline-4-carboxamido)-2,4-dimethylbenzoateYield 163.8%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of methyl 3-(2-chloroquinoline-4-carboxamido)-2,4-dimethylbenzoate (0.54 g, 0.00146 mol), tert-butyl-dimethyl-(4-piperidyloxy)silane (0.63 g, 0.00293 mol, see preparation 3) and Cs2CO3 (1.43 g, 0.0044 mol) in 1,4-dioxane (8 ml) is added Pd2(dba)3 (0.134 g, 0.000146 mol) followed by S-Phos (0.060 g, 0.000146 mol). The reaction mixture is purged with nitrogen for 5 minutes and then stirred at 80° C. After 16 hours, the reaction is cooled to ambient temperature, filtered through Celite™, and washed with EtOAc. The organic layers are combined and dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford the title compound as a black semi-solid (1.31 g, 60%, crude). Mass spectrum (m/z): 548.2 (M+1).

Workup

  1. customThe reaction mixture is purged with nitrogen for 5 minutes
  2. temperaturethe reaction is cooled to ambient temperature
  3. filtrationfiltered through Celite™
  4. washwashed with EtOAc
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c9835d7ea5e7461ca7dfc1848a3480ad
Source dataset
uspto-grants-2015_01
Patent number
US08933098B2

Reaction notes

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