3-Cyanobenzoic acid → (5s)-2-(3-Cyanophenyl)-4-(4-fluorophenyl)-4-(6-fluoro-3-pyridyl)-5-methyl-2-imidazoline

HRID 1455311ノート

反応式

HRID 1455311 の反応式
[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6](O)=O)#[N:2].[Cl-].ClC1N(C)CC[NH+]1C.ClCCl.[F:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([C:36]2[CH:37]=[N:38][C:39]([F:42])=[CH:40][CH:41]=2)([NH2:35])[C@@H:32]([NH2:34])[CH3:33])=[CH:27][CH:26]=1.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.C(N(CC)CC)C>[C:1]([C:3]1[CH:4]=[C:5]([C:6]2[NH:34][C@@H:32]([CH3:33])[C:31]([C:28]3[CH:29]=[CH:30][C:25]([F:24])=[CH:26][CH:27]=3)([C:36]3[CH:37]=[N:38][C:39]([F:42])=[CH:40][CH:41]=3)[N:35]=2)[CH:9]=[CH:10][CH:11]=1)#[N:2]

参加物

7

反応物 4

HCID 158753-Cyanobenzoic acidHCID 516892Sodium BicarbonateHCID 58649654(2S)-1-(4-fluorophenyl)-1-(6-fluoro-3-pyridyl)-1,2-propanediamineHCID 690530322-Chloro-1,3-dimethylimidazolinium chloride dichloromethane

生成物 1

HCID 178461604(5s)-2-(3-Cyanophenyl)-4-(4-fluorophenyl)-4-(6-fluoro-3-pyridyl)-5-methyl-2-imidazoline収率 98.5%

試薬・触媒・溶媒 2

HCID 6212Chloroform溶媒HCID 8471Triethylamine溶媒

実験手順

3-Cyanobenzoic acid (84 mg), triethylamine (159 μL) and. 2-chloro-1,3-dimethylimidazolinium chloride—dichloromethane 25% solution (212 μL) were added to a solution of (2S)-1-(4-fluorophenyl)-1-(6-fluoro-3-pyridyl)-1,2-propanediamine (100 mg) described in Reference Example 5-1 in chloroform (3 mL) in this order at 0° C. Then temperature of the mixture was raised to room temperature, and the mixture was stirred for 15 minutes. Saturated sodium hydrogen carbonate aqueous solution was added to the reaction mixture, and then the mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and dried over anhydrous sodium sulfate. Sodium sulfate was removed by filtration, and the organic solvent was evaporated in vacuo. The obtained crude product was stirred at 130° C. for 15 hours. The obtained oil was purified by silica gel column chromatography (C-300; hexane: ethyl acetate=1:1) to give the objective compound (140 mg).

後処理

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated sodium chloride aqueous solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. customSodium sulfate was removed by filtration
  5. customthe organic solvent was evaporated in vacuo
  6. customThe obtained crude product
  7. stirringwas stirred at 130° C. for 15 hours
  8. customThe obtained oil was purified by silica gel column chromatography (C-300; hexane: ethyl acetate=1:1)

出典と根拠

ORDレコード
ord-46601d0f6a5d4399a009658567818575
出典データセット
uspto-grants-2009_01
特許番号
US07482358B2

反応ノート

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