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 410363ノート

反応式

HRID 410363 の反応式
[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]

参加物

8

反応物 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

生成物 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 ester収率 6.2%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒HCID 6386tert-Butanol溶媒

反応条件

温度
120 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-f4898e43b09d4c29aff8a98cca58806b
出典データセット
uspto-grants-2014_06
特許番号
US08759520B2

反応ノート

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