1,2-dimethyl-1H-imidazole-5-carbaldehyde → (4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanol

HRID 526840

반응식

HRID 526840 반응식
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[C:6]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=1)=[C:5]2[Cl:25].[Li]CCCC.[CH3:31][N:32]1[C:36]([CH:37]=[O:38])=[CH:35][N:34]=[C:33]1[CH3:39]>C1COCC1>[Cl:25][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([CH:37]([C:36]3[N:32]([CH3:31])[C:33]([CH3:39])=[N:34][CH:35]=3)[OH:38])[CH:3]=2)[N:8]=[C:7]([O:12][CH3:13])[C:6]=1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=1

참가 물질

5

반응물 3

HCID 31596101,2-dimethyl-1H-imidazole-5-carbaldehydeHCID 867156276-Bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline2회HCID 178418339Butyllithium

생성물 1

HCID 86715633(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanol

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
-70 °C

실험 절차

To a flask containing 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (2.0 g, 4.64 mmol, Intermediate 5: step d) was added THF (25 mL). The solution was cooled to −70° C. and then n-BuLi (2.5 M in hexanes, 1.8 mL, 4.5 mmol) was added dropwise. After 2 minutes, 1,2-dimethyl-1H-imidazole-5-carbaldehyde (720 mg, 5.8 mmol in 5 mL THF) was introduced. The reaction mixture was allowed to warm to 0° C. over 60 minutes at which time it was quenched with aqueous NH4Cl solution. The aqueous portion was extracted with EtOAc:THF (10:1, 5×50 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated. The solid was triturated with EtOAc:Et2O (1:1), collected by filtration, rinsed with additional Et2O and dried to afford the title compound. The mother liquors were concentrated and chromatographed on silica gel (3% MeOH-DCM increasing to 10% MeOH) to provide additional title compound.

후처리

  1. temperatureto warm to 0° C. over 60 minutes at which time it
  2. customwas quenched with aqueous NH4Cl solution
  3. extractionThe aqueous portion was extracted with EtOAc:THF (10:1, 5×50 mL)
  4. washThe combined organics were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe solid was triturated with EtOAc:Et2O (1:1)
  9. filtrationcollected by filtration
  10. washrinsed with additional Et2O
  11. customdried

출처 및 근거

ORD 기록
ord-5792bd5a3d6a4c44bb5d94fbf2c174a6
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346782B2

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