3,5-Dimethylphenylboronic acid → N-(3,4-dimethoxybenzyl)-5-(3,5-dimethylphenyl)-2,3'-bipyridine-3-carboxamide

HRID 1958640Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1958640
Cl[C:2]1[N:21]=[CH:20][C:19](Cl)=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH3:17])[CH:9]=1)=[O:5].[N:23]1[CH:28]=[CH:27][CH:26]=[C:25](B(O)O)[CH:24]=1.C1(CNCC2CCCCC2)CCCCC1.[CH3:47][C:48]1[CH:49]=[C:50](B(O)O)[CH:51]=[C:52]([CH3:54])[CH:53]=1>CO.O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:17][O:16][C:10]1[CH:9]=[C:8]([CH:13]=[CH:12][C:11]=1[O:14][CH3:15])[CH2:7][NH:6][C:4]([C:3]1[C:2]([C:25]2[CH:24]=[N:23][CH:28]=[CH:27][CH:26]=2)=[N:21][CH:20]=[C:19]([C:50]2[CH:51]=[C:52]([CH3:54])[CH:53]=[C:48]([CH3:47])[CH:49]=2)[CH:18]=1)=[O:5]

Komponenten

8

Edukt 4

HCID 27343493,5-Dimethylphenylboronic acidHCID 27343783-Pyridinylboronic acidHCID 4594378Bis(cyclohexylmethyl)amine2×HCID 592333772,5-dichloro-N-(3,4-dimethoxybenzyl)nicotinamide

Produkt 1

HCID 24896566N-(3,4-dimethoxybenzyl)-5-(3,5-dimethylphenyl)-2,3'-bipyridine-3-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418851HCID 178418851, VerbindungKatalysator2×HCID 887MethanolLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

To a solution of 2,5-dichloro-N-(3,4-dimethoxybenzyl)nicotinamide (3-2, 0.100 g, 0.293 mmol) and 3-pyridyl boronic acid (0.172 g, 1.17 mmol) in methanol (1 mL) was added N,N-dicylohexylmethylamine (0.070 mL, 0.322 mmol), and bis(tri-t-butylphosphine)palladium (0.030 g, 0.058 mmol) and the system was stirred at 75° C. in an oil bath overnight. The reaction mixture was cooled to room temperature and concentrated in vacuo to afford a yellow oil. This oil (0.035 g, 0.091 mmol) was re-dissolved in dioxane (0.2 mL) and to it was added 3,5-dimethylphenyl boronic acid (0.075 g, 0.502 mmol), N,N-dicylohexylmethylamine (0.022 mL, 0.100 mmol), and bis(tri-t-butylphosphine)palladium (0.009 g, 0.018 mmol) and the system was stirred overnight at 90° C. in an oil bath. The reaction was then cooled to room temperature, partitioned between ethyl acetate and water and dried over magnesium sulfate. The reaction mixture was filtered and purified via normal phase chromatography (0→10% MeOH in DCM) followed by reverse phase chromatography (10%→65% 0.1% TFA in water: 0.1% TFA in ACN) and free based with saturated sodium carbonate to afford the title compound (1-3) as a white powder. ESI+ MS [MH]+ C28H27N3O3=454.34.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated in vacuo
  3. customto afford a yellow oil
  4. stirringthe system was stirred overnight at 90° C. in an oil bath
  5. temperatureThe reaction was then cooled to room temperature
  6. custompartitioned between ethyl acetate and water
  7. dry with materialdried over magnesium sulfate
  8. filtrationThe reaction mixture was filtered
  9. custompurified via normal phase chromatography (0→10% MeOH in DCM)

Quellen und Nachweise

ORD-Eintrag
ord-8ec9460492c84803b5a447875add88aa
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08410142B2

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