1-Methylpiperazine → 5-[6-(4-Methyl-piperazine-1-carbonyl)-pyrimidin-4-yloxy]-2,3-dihydro-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

HRID 2264613ノート

反応式

HRID 2264613 の反応式
C(Cl)(=O)C(Cl)=O.[F:7][C:8]([F:38])([F:37])[C:9]1[CH:10]=[C:11]([NH:15][C:16]([N:18]2[C:26]3[C:21](=[CH:22][C:23]([O:27][C:28]4[N:33]=[CH:32][N:31]=[C:30]([C:34]([OH:36])=O)[CH:29]=4)=[CH:24][CH:25]=3)[CH2:20][CH2:19]2)=[O:17])[CH:12]=[CH:13][CH:14]=1.[CH3:39][N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1>C(Cl)Cl.CN(C=O)C.CCOC(C)=O.C([O-])([O-])=O.[Na+].[Na+]>[F:38][C:8]([F:37])([F:7])[C:9]1[CH:10]=[C:11]([NH:15][C:16]([N:18]2[C:26]3[C:21](=[CH:22][C:23]([O:27][C:28]4[CH:29]=[C:30]([C:34]([N:43]5[CH2:44][CH2:45][N:40]([CH3:39])[CH2:41][CH2:42]5)=[O:36])[N:31]=[CH:32][N:33]=4)=[CH:24][CH:25]=3)[CH2:20][CH2:19]2)=[O:17])[CH:12]=[CH:13][CH:14]=1

参加物

8

反応物 3

HCID 531671-MethylpiperazineHCID 65578Oxalyl chlorideHCID 59596375HCID 59596375、化合物

生成物 1

HCID 595963765-[6-(4-Methyl-piperazine-1-carbonyl)-pyrimidin-4-yloxy]-2,3-dihydro-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

試薬・触媒・溶媒 4

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒HCID 10340Sodium Carbonate溶媒

実験手順

60 μl (0.7 mMol) oxalylchloride are added to a solution of 200 mg (0.45 mMol) 6-[1-(3-trifluoromethyl-phenylcarbamoyl)-2,3-dihydro-1H-indol-5-yloxy]-pyrimidine-4-carboxylic acid in 4 ml CH2Cl2 and 1 drop of DMF. After 1 h at rt, the solution is concentrated in vacuo. The residue is re-dissolved in THF and 108 μl (0.97 mMol) 1-methylpiperazine are added dropwise. After 2 h stirring, the mixture is diluted with EtOAc and sat. Na2CO3, the aqueous layer separeted off and extracted twice with EtOAc. The organic phases are washed with water and brine, dried (Na2SO4) and concentrated. Chromatography (Combi Flash; EtOAc→EtOAc/EtOH+2% Et3N 4:1) and crystallization from EtOAc gives the title compound: m.p.: 203-204° C.; TLC(EtOAc/EtOH/NH3conc. 90:10:1): Rf=0.21.

後処理

  1. concentrationthe solution is concentrated in vacuo
  2. dissolutionThe residue is re-dissolved in THF
  3. extractionextracted twice with EtOAc
  4. washThe organic phases are washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customChromatography (Combi Flash; EtOAc→EtOAc/EtOH+2% Et3N 4:1) and crystallization from EtOAc

出典と根拠

ORDレコード
ord-b11b88d8435b4f00859ff49ea7ebce20
出典データセット
uspto-grants-2010_12
特許番号
US07855215B2

反応ノート

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