Cesium carbonate → (R)-tert-butyl 1-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yl)piperidin-3-ylcarbamate

HRID 339692

Reaction equation

HRID 339692 reaction equation
FC(F)(F)S(O[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)=O.[NH:28]1[CH2:33][CH2:32][CH2:31][C@@H:30]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH2:29]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:28]4[CH2:33][CH2:32][CH2:31][C@@H:30]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:39])([CH3:38])[CH3:40])[CH2:29]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

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 1514172(3R)-3-Aminopiperidine, 3-BOC protectedHCID 866543542-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)quinolin-8-yl trifluoromethanesulfonate

Product 1

HCID 67234401(R)-tert-butyl 1-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yl)piperidin-3-ylcarbamateYield 67.5%

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), (R)-tert-butyl piperidin-3-ylcarbamate (0.026 g, 0.13 mmol), cesium carbonate (0.050 g, 0.15 mmol), Pd2dba3 (0.0046 g, 0.0051 mmol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl(0.0063 g, 0.010 mmol) were added to minimal degassed toluene and heated in a seal vial overnight at 92° C. After stirring overnight, DCM was added, solids removed through filtration (Waters filter), and the filtrate was concentrated. The crude material was purified by flash column chromatography (gradient elution of 6% NH4 in MeOH/DCM). The desired product (30 mg) was isolated, as a 1:1 mixture with the triflate starting material. The mixture was used without further purification.

Workup

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

Sources & evidence

ORD record
ord-66a428f051d6407180f76925f1c96d49
Source dataset
uspto-grants-2014_11
Patent number
US08895550B2

Linked notes

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