Diisopropylethylamine → 4-(4-Ethyl-piperazin-1-ylmethyl)-N-[3-(2-oxo-2,3-dihydro-1H-indol-6-ylamino)-phenyl]-3-trifluoromethyl-benzamide

HRID 422030Notes

Reaction equation

HRID 422030 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:17]=[C:16]3[C:12]([CH2:13][C:14](=[O:18])[NH:15]3)=[CH:11][CH:10]=2)[CH:5]=[CH:6][CH:7]=1.Cl.[CH2:20]([N:22]1[CH2:27][CH2:26][N:25]([CH2:28][C:29]2[CH:37]=[CH:36][C:32]([C:33](O)=[O:34])=[CH:31][C:30]=2[C:38]([F:41])([F:40])[F:39])[CH2:24][CH2:23]1)[CH3:21].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[CH2:20]([N:22]1[CH2:23][CH2:24][N:25]([CH2:28][C:29]2[CH:37]=[CH:36][C:32]([C:33]([NH:1][C:2]3[CH:7]=[CH:6][CH:5]=[C:4]([NH:8][C:9]4[CH:17]=[C:16]5[C:12]([CH2:13][C:14](=[O:18])[NH:15]5)=[CH:11][CH:10]=4)[CH:3]=3)=[O:34])=[CH:31][C:30]=2[C:38]([F:41])([F:39])[F:40])[CH2:26][CH2:27]1)[CH3:21]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 593970496-((3-Aminophenyl)amino)indolin-2-oneHCID 666744514-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)benzoic acid hydrochloride

Product 1

HCID 598043444-(4-Ethyl-piperazin-1-ylmethyl)-N-[3-(2-oxo-2,3-dihydro-1H-indol-6-ylamino)-phenyl]-3-trifluoromethyl-benzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-(3-amino-phenylamino)-1,3-dihydro-indol-2-one (120 mg, 0.50 mmol, prepared as described in Example 1) and 4-(4-ethyl-piperazin-1-ylmethyl)-3-trifluoromethyl-benzoic acid hydrochloride (213 mg, 0.60 mmol) in DMF (5 mL) is added N,N-diisopropylethylamine (437 μL, 2.5 mmol) followed by addition of HATU (191 mg, 0.50 mmol). The mixture is stirred at ambient temperature overnight. The mixture is diluted with EtOAc and washed with 10% Na2S2O3 aqueous solution and brine. The organic layer is separated, dried over MgSO4, and concentrated. The crude is purified by column chromatography (CH2Cl2/CH3OH=9:1) to give the desired compound. LC-MS: 538.2 (MH+).

Workup

  1. washwashed with 10% Na2S2O3 aqueous solution and brine
  2. customThe organic layer is separated
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe crude is purified by column chromatography (CH2Cl2/CH3OH=9:1)

Sources & evidence

ORD record
ord-1051cadaf7b14880899f76e049c85222
Source dataset
uspto-grants-2012_01
Patent number
US08101608B2

Reaction notes

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