Binap, (A+-)- → Tert-butyl 4-((6-(5-(3-(tert-butyldimethylsilyloxy)prop-1-ynyl)pyrazin-2-yl-amino)pyrimidin-4-ylamino)methyl)piperidine-1-carboxylate

HRID 556803Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 556803
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.[NH2:47][C:48]1[CH:53]=[N:52][C:51]([C:54]#[C:55][CH2:56][O:57][Si:58]([C:61]([CH3:64])([CH3:63])[CH3:62])([CH3:60])[CH3:59])=[CH:50][N:49]=1.Cl[C:66]1[N:71]=[CH:70][N:69]=[C:68]([NH:72][CH2:73][CH:74]2[CH2:79][CH2:78][N:77]([C:80]([O:82][C:83]([CH3:86])([CH3:85])[CH3:84])=[O:81])[CH2:76][CH2:75]2)[CH:67]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[Si:58]([O:57][CH2:56][C:55]#[C:54][C:51]1[N:52]=[CH:53][C:48]([NH:47][C:66]2[N:71]=[CH:70][N:69]=[C:68]([NH:72][CH2:73][CH:74]3[CH2:75][CH2:76][N:77]([C:80]([O:82][C:83]([CH3:86])([CH3:85])[CH3:84])=[O:81])[CH2:78][CH2:79]3)[CH:67]=2)=[N:49][CH:50]=1)([C:61]([CH3:64])([CH3:63])[CH3:62])([CH3:59])[CH3:60]

Komponenten

8

Edukt 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 45787122tert-Butyl 4-(((6-chloropyrimidin-4-yl)amino)methyl)piperidine-1-carboxylateHCID 59613433HCID 59613433, Verbindung

Produkt 1

HCID 66746379Tert-butyl 4-((6-(5-(3-(tert-butyldimethylsilyloxy)prop-1-ynyl)pyrazin-2-yl-amino)pyrimidin-4-ylamino)methyl)piperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
145 °C

Versuchsvorschrift

2,2′-Bis(diphenylphosphino)-1,1′-binaphthalene (56 mg, 0.09 mmol) and palladium acetate (4 mg, 0.015 mmol) were suspended in 5 mL toluene (5 mL) and degassed over 10 minutes under a stream of nitrogen gas. 2-Amino-5-(3-(tert-butyldimethyl-silyloxy)prop-1-ynyl)pyrazine (50 mg, 0.15 mmol) and tert-butyl 4-((6-chloropyrimidin-4-ylamino)methyl)-piperidine-1-carboxylate (40 mg, 0.15 mmol), in anhydrous and degassed DMF (500 μL), and sodium tert-butoxide (46 mg, 0.45 mmol) were added and the reaction mixture was heated at 145° C. for 30 minutes by microwave irradiation. The mixture was evaporated to dryness. The residue was partitioned between water and dichloromethane and the aqueous phase was extracted with dichloromethane. The combined organic phases were dried (Na2SO4) and concentrated. The residue was redissolved in methanol and filtered through a PS—SH column. The filtrate was evaporated to dryness to give crude tert-butyl 4-((6-(5-(3-(tert-butyldimethylsilyloxy)prop-1-ynyl)pyrazin-2-yl-amino)pyrimidin-4-ylamino)methyl)piperidine-1-carboxylate which was used directly for the next step.

Aufarbeitung

  1. customdegassed over 10 minutes under a stream of nitrogen gas
  2. additionwere added
  3. customThe mixture was evaporated to dryness
  4. customThe residue was partitioned between water and dichloromethane
  5. extractionthe aqueous phase was extracted with dichloromethane
  6. dry with materialThe combined organic phases were dried (Na2SO4)
  7. concentrationconcentrated
  8. dissolutionThe residue was redissolved in methanol
  9. filtrationfiltered through a PS—SH column
  10. customThe filtrate was evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-fae2d583a7b1494eaf57ad08fb817456
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08058045B2

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