Potassium Carbonate → 1-(3-((4-(Piperidin-1-yl)-2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)phenyl)carbamoyl)benzyl)-1H-indole-4-carboxylic acid

HRID 625272ノート

反応式

HRID 625272 の反応式
[NH:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([C:10]([O:12]C)=[O:11])[C:4]=2[CH:3]=[CH:2]1.Cl[CH2:15][C:16]1[CH:17]=[C:18]([CH:54]=[CH:55][CH:56]=1)[C:19]([NH:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)=[CH:24][C:23]=1[C:34]1[CH:35]=[C:36]([CH:51]=[CH:52][N:53]=1)[C:37]([NH:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[C:43]([C:47]([F:50])([F:49])[F:48])[CH:42]=1)=[O:38])=[O:20].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[N:28]1([C:25]2[CH:26]=[CH:27][C:22]([NH:21][C:19]([C:18]3[CH:17]=[C:16]([CH:56]=[CH:55][CH:54]=3)[CH2:15][N:1]3[C:9]4[CH:8]=[CH:7][CH:6]=[C:5]([C:10]([OH:12])=[O:11])[C:4]=4[CH:3]=[CH:2]3)=[O:20])=[C:23]([C:34]3[CH:35]=[C:36]([C:37](=[O:38])[NH:39][CH2:40][C:41]4[CH:46]=[CH:45][CH:44]=[C:43]([C:47]([F:48])([F:49])[F:50])[CH:42]=4)[CH:51]=[CH:52][N:53]=3)[CH:24]=2)[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1

参加物

5

反応物 3

HCID 11430Potassium CarbonateHCID 2733668methyl 1H-indole-4-carboxylateHCID 665867362-(2-(3-(chloromethyl)benzamido)-5-(piperidin-1-yl)phenyl)-N-(3-(trifluoromethyl)benzyl)-isonicotinamide

生成物 1

HCID 665881211-(3-((4-(Piperidin-1-yl)-2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)phenyl)carbamoyl)benzyl)-1H-indole-4-carboxylic acid収率 48.3%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 10.5 mg of methyl 1H-indole-4-carboxylate, 18.2 mg of 2-(2-(3-(chloromethyl)benzamido)-5-(piperidin-1-yl)phenyl)-N-(3-(trifluoromethyl)benzyl)-isonicotinamide 8.1a, and excess potassium carbonate in 300 μL of DMF was stirred for 24 h. The solvent was evaporated and the residue was purified by silica gel chromatography. The product was dissolved in 1 mL of 4:1 THF/water and treated with 10 mg of LiOH.H2O. After stirring 4 days at 70° C. the reaction mixture was acidified with 3.0 N hydrochloric acid and then extracted with ethyl acetate. The aqueous phase was washed with ethyl acetate, and the combined organic extracts washed with brine and dried (NaSO4). The residue was purified by reverse phase HPLC eluting with 0.1% TFA in a water/acetonitrile gradient to give 10.6 mg of product. MS (ES, m/z) 732.4 [M+H]+.

後処理

  1. customThe solvent was evaporated
  2. customthe residue was purified by silica gel chromatography
  3. dissolutionThe product was dissolved in 1 mL of 4:1 THF/water
  4. additiontreated with 10 mg of LiOH.H2O
  5. stirringAfter stirring 4 days at 70° C. the reaction mixture
  6. extractionextracted with ethyl acetate
  7. washThe aqueous phase was washed with ethyl acetate
  8. washthe combined organic extracts washed with brine
  9. dry with materialdried (NaSO4)
  10. customThe residue was purified by reverse phase HPLC
  11. washeluting with 0.1% TFA in a water/acetonitrile gradient

出典と根拠

ORDレコード
ord-5209ac302259498abdcb13fbce394f23
出典データセット
uspto-grants-2016_04
特許番号
US09301951B2

反応ノート

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