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 1188605ノート

反応式

HRID 1188605 の反応式
[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

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 167845palladium(II) acetate触媒

反応条件

温度
70 °C

実験手順

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+).

後処理

  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)

出典と根拠

ORDレコード
ord-688769b70cc24a66acb6204eac24b6e4
出典データセット
uspto-grants-2014_03
特許番号
US08673948B2

反応ノート

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