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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
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HRID 410358 반응식
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
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참가 물질

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반응물 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

생성물 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
수율 11%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매

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온도
130 °C

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-0acd23d7ee0a49cd964f7e9b55a36983
출처 데이터셋
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08759520B2

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