1-(benzyloxymethyl)-2-phenyl-1H-imidazole → 4-((1-(benzyloxymethyl)-2-phenyl-1H-imidazol-5-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrile

HRID 2104956노트

반응식

HRID 2104956 반응식
[CH2:1]([O:8][CH2:9][N:10]1[CH:14]=[CH:13][N:12]=[C:11]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]C(CC)C.[CH2:26]([O:28][C:29]1[CH:30]=[C:31]([O:46][CH:47]([CH3:49])[CH3:48])[C:32]([F:45])=[C:33]([CH:44]=1)/[CH:34]=[N:35]/[C:36]1[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=1)[CH3:27]>C1COCC1>[CH2:1]([O:8][CH2:9][N:10]1[C:14]([N:35]([CH2:34][C:33]2[CH:44]=[C:29]([O:28][CH2:26][CH3:27])[CH:30]=[C:31]([O:46][CH:47]([CH3:49])[CH3:48])[C:32]=2[F:45])[C:36]2[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=2)=[CH:13][N:12]=[C:11]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

5

반응물 3

HCID 578039651-(benzyloxymethyl)-2-phenyl-1H-imidazoleHCID 178418400CID 53628100HCID 178466720HCID 178466720, 화합물

생성물 1

HCID 688133704-((1-(benzyloxymethyl)-2-phenyl-1H-imidazol-5-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrile수율 24.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

To a solution of Intermediate 15.1 (100 mg, 0.378 mmol) in 2 mL THF at 0° C., was added sec-BuLi (0.81 M in cyclohexane, 514 μL, 0.416 mmol). The mixture was stirred at 0° C. for 10 min, then a solution of Intermediate 7.3 (123 mg, 0.378 mmol) in 0.6 mL THF was added dropwise. The mixture was stirred at 0° C. for 30 min and rt 1 h, then was quenched with sat. NH4Cl. The mixture was diluted with EtOAc, washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 75% EtOAc/hexanes gradient) followed by preparative HPLC purification to afford 53.7 mg of Intermediate 15.2.

후처리

  1. stirringThe mixture was stirred at 0° C. for 30 min and rt 1 h
  2. customwas quenched with sat. NH4Cl
  3. additionThe mixture was diluted with EtOAc
  4. washwashed with H2O and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography (0 to 75% EtOAc/hexanes gradient)
  8. customfollowed by preparative HPLC purification

출처 및 근거

ORD 기록
ord-f2d3969455624f90b068529c099f105f
출처 데이터셋
uspto-grants-2009_08
특허 번호
US07576098B2

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