2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 3-(3-{3-[4-(4-Biphenyl-2-ylmethyl-piperazin-1-yl)-benzyl]-2-imino-2,3-dihydro-benzoimidazol-1-yl}-propoxy)-benzoic acid ethyl ester

HRID 410363Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 410363
[CH2:1]([O:3][C:4](=[O:33])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][N:15]2[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[N:17]([CH2:24][C:25]3[CH:30]=[CH:29][C:28](Br)=[CH:27][CH:26]=3)[C:16]2=[NH:32])[CH:6]=1)[CH3:2].CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[C:74]1([C:87]2[CH:92]=[CH:91][CH:90]=[CH:89][CH:88]=2)[CH:79]=[CH:78][CH:77]=[CH:76][C:75]=1[CH2:80][N:81]1[CH2:86][CH2:85][NH:84][CH2:83][CH2:82]1>C1(C)C=CC=CC=1.C(O)(C)(C)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:1]([O:3][C:4](=[O:33])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][N:15]2[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[N:17]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([N:84]4[CH2:85][CH2:86][N:81]([CH2:80][C:75]5[CH:76]=[CH:77][CH:78]=[CH:79][C:74]=5[C:87]5[CH:92]=[CH:91][CH:90]=[CH:89][CH:88]=5)[CH2:82][CH2:83]4)=[CH:27][CH:26]=3)[C:16]2=[NH:32])[CH:6]=1)[CH3:2]

Komponenten

8

Edukt 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 183819371-Biphenyl-2-ylmethyl-piperazineHCID 23676156Sodium t-butoxideHCID 585649753-(3-{3-(4-Bromo-benzyl)-2-imino-2,3-dihydro-benzoimidazol-1-yl]-propoxy}-benzoic acid ethyl ester

Produkt 1

HCID 585649503-(3-{3-[4-(4-Biphenyl-2-ylmethyl-piperazin-1-yl)-benzyl]-2-imino-2,3-dihydro-benzoimidazol-1-yl}-propoxy)-benzoic acid ethyl esterAusbeute 6,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittelHCID 6386tert-ButanolLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a mixture of 3-{3-[3-(4-bromo-benzyl)-2-imino-2,3-dihydro-benzoimidazol-1-yl]-propoxy}-benzoic acid ethyl ester (0.50 g, 0.99 mmol), sodium tert-butoxide (0.26 g, 2.67 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (33 mg, 0.07 mmol) and Pd(OAc)2 (22 mg, 0.10 mmol) at rt was added a degassed solution of 1-biphenyl-2-ylmethyl-piperazine (0.25 g, 0.99 mmol) in toluene (15 ml) and tert-butanol (3 ml). The reaction was heated to 120° C. where it was maintained fro 3 d. After this time, the reaction was cooled to rt and concentrated under reduced pressure. The material that remained was partitioned between H2O and EtOAc and the organic phase was separated, dried (Na2SO4), filtered and concentrated under reduced pressure. Purification by chromatography on silica eluting with EtOAc/hexane provided 3-(3-{3-[4-(4-biphenyl-2-ylmethyl-piperazin-1-yl)-benzyl]-2-imino-2,3-dihydro-benzoimidazol-1-yl}-propoxy)-benzoic acid ethyl ester (42 mg, 6%). HPLC-MS 680 [M+1]+, 341.

Aufarbeitung

  1. temperaturewas maintained fro 3 d
  2. temperatureAfter this time, the reaction was cooled to rt
  3. concentrationconcentrated under reduced pressure
  4. customThe material that remained was partitioned between H2O and EtOAc
  5. customthe organic phase was separated
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification by chromatography on silica eluting with EtOAc/hexane

Quellen und Nachweise

ORD-Eintrag
ord-f4898e43b09d4c29aff8a98cca58806b
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08759520B2

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