Binap, (A+-)- → 5-{1-[2-((S)-1-Phenyl-ethylamino)-pyridin-4-yl]-1H-indazol-3-yl}-(1S,4S)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

HRID 729528

Reaktionsgleichung

Reaktionsgleichung von HRID 729528
Cl[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][CH:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH3:19])[CH:12]=2)[N:3]=1.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@H:72]12[CH2:78][C@H:75]([NH:76][CH2:77]1)[CH2:74][N:73]2[C:79]([O:81][C:82]([CH3:85])([CH3:84])[CH3:83])=[O:80].CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:82]([O:81][C:79]([N:73]1[CH2:74][C@@H:75]2[CH2:78][C@H:72]1[CH2:77][N:76]2[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C@H:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH3:19])[CH:12]=2)[N:3]=1)=[O:80])([CH3:85])([CH3:83])[CH3:84]

Komponenten

8

Edukt 4

HCID 634876Binap, (A+-)-HCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptaneHCID 23676156Sodium t-butoxideHCID 68905958[4-(3-Chloro-indazol-1-yl)-pyridin-2-yl]-(1-phenyl-ethyl)-amine

Produkt 1

HCID 689115445-{1-[2-((S)-1-Phenyl-ethylamino)-pyridin-4-yl]-1H-indazol-3-yl}-(1S,4S)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a solution of [4-(3-chloro-indazol-1-yl)-pyridin-2-yl]-(1-phenyl-ethyl)-amine (0.17 g, 0.48 mmol) in toluene (3 mL) under nitrogen were added palladium acetate (0.011 g, 0.05 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.03 g, 0.05 mmol), and t-butyl(1S,4S)-(−)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (0.14 g, 0.72 mmol), followed by sodium t-butoxide (0.13 g, 1.3 mmol). The resulting mixture was stirred at 90° C. for 20 h. After cooling to room temperature, the reaction was diluted with methylene chloride and washed with saturated sodium bicarbonate and brine; dried (MgSO4). Flash chromatography of the crude product mixture with 25:10:65, 40:10:50, 50:10:40, 60:10:30, and 70:10:20 EtOAc-CH2Cl2-Hexane gave the title compound. MS (ES+): 511.4 [M+H]+, 509.2 [M−H]−.

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. washwashed with saturated sodium bicarbonate and brine
  3. dry with materialdried (MgSO4)

Quellen und Nachweise

ORD-Eintrag
ord-237588a0e26143cb8f497c813cf87270
Quelldatensatz
uspto-grants-2009_09
Patentnummer
US07582631B2

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