Methanol → Methyl 4-chloro-3-(3-{[5-cyano-2-propyl-4-(trifluoromethyl)-1H-indol-1-yl]methyl}-1,2,4-oxadiazol-5-yl)benzoate

HRID 2102111노트

반응식

HRID 2102111 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][C:3]=1[C:9]1[O:13][N:12]=[C:11]([CH2:14][N:15]2[C:23]3[C:18](=[C:19]([C:26]([F:29])([F:28])[F:27])[C:20]([C:24]#[N:25])=[CH:21][CH:22]=3)[CH:17]=[C:16]2[CH2:30][CH2:31][CH3:32])[N:10]=1.[CH3:33][OH:34].CN([CH:38]=[O:39])C>CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:33]([O:39][CH3:38])=[O:34])=[CH:4][C:3]=1[C:9]1[O:13][N:12]=[C:11]([CH2:14][N:15]2[C:23]3[C:18](=[C:19]([C:26]([F:28])([F:29])[F:27])[C:20]([C:24]#[N:25])=[CH:21][CH:22]=3)[CH:17]=[C:16]2[CH2:30][CH2:31][CH3:32])[N:10]=1

참가 물질

5

반응물 3

HCID 887MethanolHCID 6228DimethylformamideHCID 578001721-{[5-(2-Chloro-5-iodophenyl)-1,2,4-oxadiazol-3-yl]methyl}-2-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

생성물 1

HCID 57800414Methyl 4-chloro-3-(3-{[5-cyano-2-propyl-4-(trifluoromethyl)-1H-indol-1-yl]methyl}-1,2,4-oxadiazol-5-yl)benzoate수율 64%

시약·촉매·용매 1

HCID 167845palladium(II) acetate촉매

반응 조건

온도
70 °C

실험 절차

A solution containing 1-{[5-(2-chloro-5-iodophenyl)-1,2,4-oxadiazol-3-yl]methyl}-2-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (Example 291) (0.378 g, 0.662 mmol), 1,1-bisdiphenylphosphinoferrocene (0.073 g, 0.132 mmol), E3N (1.0 mL, 13.6 mmol), Pd(OAc)2 (0.032 g, 0.132 mmol), anhydrous MeOH (2.0 mL) and anhydrous DMF (20 mL). The mixture was then stirred at 70° C. under a carbon monoxide atmosphere for a period of 4 h and then allowed to cooled to rt. The reaction was partitioned between NaHCO3 and EtOAc, dried (MgSO4) and concentrated to dryness. The mixture was purified on a biotage prepak column (0-10% EtOAc-hexanes gradient) to give 0.214 g (64% yield) of pure product: MS (ES) m/z 502 (M+).

후처리

  1. temperatureto cooled to rt
  2. customThe reaction was partitioned between NaHCO3 and EtOAc
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated to dryness
  5. customThe mixture was purified on a biotage prepak column (0-10% EtOAc-hexanes gradient)

출처 및 근거

ORD 기록
ord-c8a37e7d0f7244bea4fc1a09eef90d40
출처 데이터셋
uspto-grants-2009_08
특허 번호
US07572820B2

반응 노트

불러오는 중…