Cesium carbonate → 3-(3-Chloro-5-{5-[4-phenyl-5-(trifluoromethyl)-2-thienyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)propanoic acid

HRID 423366

反応式

HRID 423366 の反応式
[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[N:15]=[C:14]([C:16]4[S:17][C:18]([C:27]([F:30])([F:29])[F:28])=[C:19]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=5)[CH:20]=4)[O:13][N:12]=3)[CH:9]=2)[NH:4][CH:3]=1.Br[CH2:32][CH2:33][C:34]([O-:36])=[O:35].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[N:15]=[C:14]([C:16]4[S:17][C:18]([C:27]([F:30])([F:28])[F:29])=[C:19]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=5)[CH:20]=4)[O:13][N:12]=3)[CH:9]=2)[N:4]([CH2:32][CH2:33][C:34]([OH:36])=[O:35])[CH:3]=1

参加物

5

反応物 3

HCID 10796Cesium carbonateHCID 6993466Beta-bromopropionateHCID 59318343HCID 59318343、化合物

生成物 1

HCID 249863833-(3-Chloro-5-{5-[4-phenyl-5-(trifluoromethyl)-2-thienyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)propanoic acid収率 23%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
131 °C

実験手順

D8 (86 mg), 3-bromopropionate (52 mg), Cs2CO3 (126 mg) and DMF (1 ml) were placed in a microwave vial and stirred at 131° C. in the microwave reactor for 1.5 hours. The reaction mixture was then evaporated to dryness and treated with 2M aq. NaOH and EtOH (20 ml). This solution was stirred at 50° C. for 4 hours and then neutralised with HCl and evaporated to remove the EtOH. The aqueous solution was then extracted twice with EtOAc and the combined extracts evaporated. The residue was dissolved in DMSO, filtered, treated with MeCN causing precipitation of the product which was filtered and washed with MeCN to give the title compound (23 mg) as an off-white solid. δH (d6-DMSO, 400 MHz): 2.47-2.57 (solvent+2H) 4.37 (2H, t), 7.51-7.59 (5H, m), 7.72 (1H, s), 7.76 (1H, d), 7.89 (1H, d), 8.17 (1H, s), 8.25 (1H, s). MS (ES): C24H16ClF3N3O2S requires 517; found 516 (M−H+).

後処理

  1. customThe reaction mixture was then evaporated to dryness
  2. additiontreated with 2M aq. NaOH and EtOH (20 ml)
  3. stirringThis solution was stirred at 50° C. for 4 hours
  4. customevaporated
  5. customto remove the EtOH
  6. extractionThe aqueous solution was then extracted twice with EtOAc
  7. customthe combined extracts evaporated
  8. dissolutionThe residue was dissolved in DMSO
  9. filtrationfiltered
  10. additiontreated with MeCN causing precipitation of the product which
  11. filtrationwas filtered
  12. washwashed with MeCN

出典と根拠

ORDレコード
ord-12d84e9017df496e98d690f567483705
出典データセット
uspto-grants-2012_01
特許番号
US08101775B2

関連ノート

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