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

HRID 2264613Notes

Reaction equation

HRID 2264613 reaction equation
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

Participants

8

Reactant 3

HCID 531671-MethylpiperazineHCID 65578Oxalyl chlorideHCID 59596375HCID 59596375, compound

Product 1

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

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-b11b88d8435b4f00859ff49ea7ebce20
Source dataset
uspto-grants-2010_12
Patent number
US07855215B2

Reaction notes

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