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Binap, (A+-)- → 3-[4-(4-Biphenyl-2-ylmethyl-piperazin-1-yl)-benzyl]-1-[3-(4-fluoro-phenoxy)-propyl]-5-methyl-1,3-dihydro-benzoimidazol-2-ylideneamine

HRID 410358
ノート
印刷プレビュー

反応式

HRID 410358 の反応式
C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.[C:47]1([C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)[CH:52]=[CH:51][CH:50]=[CH:49][C:48]=1[CH2:53][N:54]1[CH2:59][CH2:58][NH:57][CH2:56][CH2:55]1.Br[C:67]1[CH:95]=[CH:94][C:70]([CH2:71][N:72]2[C:76]3[CH:77]=[C:78]([CH3:81])[CH:79]=[CH:80][C:75]=3[N:74]([CH2:82][CH2:83][CH2:84][O:85][C:86]3[CH:91]=[CH:90][C:89]([F:92])=[CH:88][CH:87]=3)[C:73]2=[NH:93])=[CH:69][CH:68]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:47]1([C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)[CH:52]=[CH:51][CH:50]=[CH:49][C:48]=1[CH2:53][N:54]1[CH2:55][CH2:56][N:57]([C:67]2[CH:95]=[CH:94][C:70]([CH2:71][N:72]3[C:76]4[CH:77]=[C:78]([CH3:81])[CH:79]=[CH:80][C:75]=4[N:74]([CH2:82][CH2:83][CH2:84][O:85][C:86]4[CH:87]=[CH:88][C:89]([F:92])=[CH:90][CH:91]=4)[C:73]3=[NH:93])=[CH:69][CH:68]=2)[CH2:58][CH2:59]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 634876Binap, (A+-)-HCID 183819371-Biphenyl-2-ylmethyl-piperazineHCID 23676156Sodium t-butoxideHCID 585649693-(4-Bromo-benzyl)-1-[3-(4-fluoro-phenoxy)-propyl]-5-methyl-1,3-dihydrobenzoimidazol-2-ylideneamine

生成物 1

HCID 585649673-[4-(4-Biphenyl-2-ylmethyl-piperazin-1-yl)-benzyl]-1-[3-(4-fluoro-phenoxy)-propyl]-5-methyl-1,3-dihydro-benzoimidazol-2-ylideneamine
収率 11%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒

反応条件

温度
130 °C

実験手順

3-(4-Bromo-benzyl)-1-[3-(4-fluoro-phenoxy)-propyl]-5-methyl-1,3-dihydrobenzoimidazol-2-ylideneamine, hydrobromide salt (20 mg, 0.036 mmol) was partitioned between aqueous NaOH and EtOAc. The organic phase was separated, dried (Na2SO4) and concentrated under reduced pressure to provide 3-(4-bromo-benzyl)-1-[3-(4-fluoro-phenoxy)-propyl]-5-methyl-1,3-dihydrobenzoimidazol-2-ylideneamine (0.036 mmol). To a degassed solution of Pd(OAc)2 (0.04 mg, 0.16 □mol) and BINAP (0.44 mg, 0.71 mmol) in toluene (8 ml) at 40° C. was added 1-biphenyl-2-ylmethyl-piperazine (18 mg, 0.071 mmol) followed by 3-(4-bromo-benzyl)-1-[3-(4-fluoro-phenoxy)-propyl]-5-methyl-1,3-dihydrobenzoimidazol-2-ylideneamine (0.036 mmol) and sodium t-butoxide (4.8 mg, 0.05 mmol). The suspension was then heated to 130° C. where it was maintained for 20 h. After this time, the mixture was filtered and then the filtrate was partitioned between H2O and EtOAc. The organic phase was separated and concentrated under reduced pressure to provide the crude product. Purification by preparative HPLC gave 3-[4-(4-biphenyl-2-ylmethyl-piperazin-1-yl)-benzyl]-1-[3-(4-fluoro-phenoxy)-propyl]-5-methyl-1,3-dihydro-benzoimidazol-2-ylideneamine (2.5 mg, 11%). HPLC-MS 640 [M+1]+, 320 (100%).

後処理

  1. temperaturewas maintained for 20 h
  2. filtrationAfter this time, the mixture was filtered
  3. customthe filtrate was partitioned between H2O and EtOAc
  4. customThe organic phase was separated
  5. concentrationconcentrated under reduced pressure
  6. customto provide the crude product
  7. customPurification by preparative HPLC

出典と根拠

ORDレコード
ord-0acd23d7ee0a49cd964f7e9b55a36983
出典データセット
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08759520B2

反応ノート

読み込み中…

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