5-Bromopyrimidine → 4-(Pyrimidin-5-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

HRID 547914

Reaktionsgleichung

Reaktionsgleichung von HRID 547914
Br[C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1.[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([NH2:21])[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].O(C(C)(C)C)[K]>C1(C)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].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>[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([NH:21][C:2]2[CH:3]=[N:4][CH:5]=[N:6][CH:7]=2)[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:9])[CH3:10]

Komponenten

7

Edukt 3

HCID 783445-BromopyrimidineHCID 12682914-Amino-1-Boc-piperidineHCID 178418922HCID 178418922, Verbindung

Produkt 1

HCID 671982114-(Pyrimidin-5-ylamino)-piperidine-1-carboxylic acid tert-butyl esterAusbeute 47 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 634876Binap, (A+-)-KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittel

Versuchsvorschrift

A mixture of 5-bromo-pyrimidine (1.59 g, 10.00 mmol, 1.0 equiv; commercially available), 4-amino-piperidine-1-carboxylic acid tert-butyl ester (2.00 g, 10.00 mmol, 1.0 equiv), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (0.25 g, 0.40 mmol, 0.04 equiv), tris(dibenzylideneacetone)dipalladium(0) (0.21 g, 0.20 mmol, 0.02 equiv) and KOtert-Bu (1.35 g, 12.01 mmol, 1.2 equiv) in toluene (10 mL) was heated under Ar by microwave irradiation to 100° C. for 2 h. The crude reaction mixture was filtered through Hyflo Super Cel, a sat. solution of sodium chloride (100 mL) was added and the mixture extracted with ethyl acetate (3×50 mL). The combined organic phases were concentrated by evaporation under reduced pressure and the residue purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane (+1% triethylamine)/ethyl acetate to provide 1.30 g (47%) of the title compound. MS (ISP): 279.1 [M+H]+.

Aufarbeitung

  1. customThe crude reaction mixture
  2. filtrationwas filtered through Hyflo Super Cel
  3. additiona sat. solution of sodium chloride (100 mL) was added
  4. extractionthe mixture extracted with ethyl acetate (3×50 mL)
  5. concentrationThe combined organic phases were concentrated by evaporation under reduced pressure
  6. customthe residue purified by silica column chromatography
  7. washeluting with a gradient of heptane (+1% triethylamine)/ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-3f32390041ba44ada63f8874ed90e3fd
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07939661B2

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