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

HRID 1041982

Reaktionsgleichung

Reaktionsgleichung von HRID 1041982
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

Komponenten

6

Edukt 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

Produkt 1

HCID 67234401(R)-tert-butyl 1-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yl)piperidin-3-ylcarbamateAusbeute 67,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Reaktionsbedingungen

Temperatur
92 °C

Versuchsvorschrift

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), Pd2 dba3 (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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-09c16e0a993e40acb0b1abb87e088ceb
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08557809B2

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