Cesium carbonate → Trifluoromethanesulfonate

HRID 1041981Notes

Reaction equation

HRID 1041981 reaction equation
[F:1][C:2]([F:27])([F:26])[S:3]([O:6][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:16]=1[N:15]=[C:14]([C:17]1[N:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]3=[N:19][N:18]=1)[CH:13]=[CH:12]2)(=[O:5])=[O:4].[CH3:28][CH:29]1[CH2:34][CH2:33][CH2:32][NH:31][CH2:30]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:19]1[N:18]=[C:17]([C:14]2[CH:13]=[CH:12][C:11]3[C:16](=[C:7]([N:31]4[CH2:32][CH2:33][CH2:34][CH:29]([CH3:28])[CH2:30]4)[CH:8]=[CH:9][CH:10]=3)[N:15]=2)[N:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=12.[O-:6][S:3]([C:2]([F:27])([F:26])[F:1])(=[O:5])=[O:4]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 790813-MethylpiperidineHCID 634876Binap, (A+-)-HCID 866543542-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)quinolin-8-yl trifluoromethanesulfonate

Product 2

HCID 2758875TrifluoromethanesulfonateHCID 461789032-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)-8-(3-methylpiperidin-1-yl)quinoline

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
92 °C

Procedure

2-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)quinolin-8-yl trifluoromethanesulfonate (0.040 g, 0.10 mmol), 3-methylpiperidine (0.016 mL, 0.13 mmol), cesium carbonate (0.050 g, 0.15 mmol), Pd2 dba3 (0.005 g, 0.005 mmol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.006 g, 0.01 mmol) were added to minimal degassed toluene and heated to 92° C. overnight in a sealed tube. After stirring overnight, DCM was added, and solids removed through filtration (Waters filter), followed by concentration in vacuo. The crude mixture was then purified by flash column chromatography (gradient elution of 6% NH4 in MeOH/DCM). The desired product was isolated, along with triflate starting material. The mixture was then treated with 3 N HCl aqueous at 95° C. overnight. The reaction was then cooled and solids removed by filtration. The filtrate was purified by flash column chromatography (gradient elution of 6% NH4 in MeOH/DCM (Rf ˜0.1 in 6% NH4 in MeOH (5%) and DCM (95%)). The desired product was isolated as a yellow solid, 0.005 g (15% yield). MS ESI (+) m/z 344.3 (M+1) detected.

Workup

  1. customto minimal degassed toluene
  2. additionDCM was added
  3. customsolids removed through filtration (Waters filter)
  4. concentrationfollowed by concentration in vacuo
  5. customThe crude mixture was then purified by flash column chromatography (gradient elution of 6% NH4 in MeOH/DCM)

Sources & evidence

ORD record
ord-400fc03888d044cb9bb9bda8273488ee
Source dataset
uspto-grants-2013_10
Patent number
US08557809B2

Reaction notes

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