1-benzyloxymethyl-1H-benzimidazole → 4-((1-(benzyloxymethyl)-1H-benzo[d]imidazol-2-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrile

HRID 2104951노트

반응식

HRID 2104951 반응식
[CH2:1]([O:8][CH2:9][N:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]=[CH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.[CH2:24]([O:26][C:27]1[CH:28]=[C:29]([O:44][CH:45]([CH3:47])[CH3:46])[C:30]([F:43])=[C:31]([CH:42]=1)/[CH:32]=[N:33]/[C:34]1[CH:41]=[CH:40][C:37]([C:38]#[N:39])=[CH:36][CH:35]=1)[CH3:25]>C1COCC1>[CH2:1]([O:8][CH2:9][N:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]=[C:11]1[N:33]([CH2:32][C:31]1[CH:42]=[C:27]([O:26][CH2:24][CH3:25])[CH:28]=[C:29]([O:44][CH:45]([CH3:47])[CH3:46])[C:30]=1[F:43])[C:34]1[CH:41]=[CH:40][C:37]([C:38]#[N:39])=[CH:36][CH:35]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

5

반응물 3

HCID 113223751-benzyloxymethyl-1H-benzimidazoleHCID 178418339ButyllithiumHCID 178466720HCID 178466720, 화합물

생성물 1

HCID 688137704-((1-(benzyloxymethyl)-1H-benzo[d]imidazol-2-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrile수율 80.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

반응 조건

온도
-78 °C

실험 절차

To a solution of Intermediate 10.1 (50.0 mg, 0.210 mmol) in 2 mL THF at −78° C. was added 1.6 M solution of BuLi in THF (144 μL, 0.231 mmol). The mixture was stirred at −78° C. for 15 min, then a solution of Intermediate 7.3 (69 mg, 0.210 mmol) in 0.6 mL THF was added dropwise. The mixture was stirred at −78° C. for 30 min, was allowed to warm to rt over 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 40% EtOAc/hexanes gradient) to afford 95 mg of Intermediate 10.2 as a pale yellow oil.

후처리

  1. stirringThe mixture was stirred at −78° C. for 30 min
  2. temperatureto warm to rt over 1 h
  3. customwas quenched with sat. NH4Cl
  4. additionThe mixture was diluted with EtOAc
  5. washwashed with H2O and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography (0 to 40% EtOAc/hexanes gradient)

출처 및 근거

ORD 기록
ord-3fbdc59e942440f0ba4207a869cc4fd1
출처 데이터셋
uspto-grants-2009_08
특허 번호
US07576098B2

반응 노트

불러오는 중…