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 410363노트

반응식

HRID 410363 반응식
[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]

참가 물질

8

반응물 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

생성물 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 ester수율 6.2%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매HCID 6386tert-Butanol용매

반응 조건

온도
120 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-f4898e43b09d4c29aff8a98cca58806b
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759520B2

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