Diisopropylethylamine → 3-(2-Ethoxypyridin-3-yl)-3-[4-(4-methylpiperazin-1-ylmethyl)phenylamino]-2-oxo-2,3-dihydro-1H-indole-5-carbonitrile

HRID 469200Notes

Reaction equation

HRID 469200 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.Cl[C:17]1([C:29]2[C:30]([O:35][CH2:36][CH3:37])=[N:31][CH:32]=[CH:33][CH:34]=2)[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:26]#[N:27])[CH:24]=2)[NH:19][C:18]1=[O:28].CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>ClCCl>[CH2:36]([O:35][C:30]1[C:29]([C:17]2([NH:15][C:12]3[CH:13]=[CH:14][C:9]([CH2:8][N:5]4[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]4)=[CH:10][CH:11]=3)[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]#[N:27])[CH:24]=3)[NH:19][C:18]2=[O:28])=[CH:34][CH:33]=[CH:32][N:31]=1)[CH3:37]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 31539964-((4-Methylpiperazin-1-yl)methyl)anilineHCID 670485043-Chloro-3-(2-ethoxypyridin-3-yl)-2-oxoindoline-5-carbonitrile

Product 1

HCID 671980643-(2-Ethoxypyridin-3-yl)-3-[4-(4-methylpiperazin-1-ylmethyl)phenylamino]-2-oxo-2,3-dihydro-1H-indole-5-carbonitrileYield 103.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-(4-Methyl-piperazin-1-ylmethyl)phenylamine (425 mg, 2.07 mmol) was added to a solution of 3-chloro-3-(2-ethoxypyridin-3-yl)-2-oxo-2,3-dihydro-1H-indole-5-carbonitrile (500 mg, 1.59 mmol) in dichloromethane (50 ml) and DIPEA (0.27 ml, 159 mmol) at 0° C. The reaction mixture was stirred at room temperature for 2 h and then an aqueous NaHCO3 solution was added. The aqueous reaction mixture was extracted with dichloromethane. The combined organic phase was dried over magnesium sulfate, filtered and concentrated at reduced pressure. Purification by chromatography (silica gel, 0-20% methanol in dichloromethane) afforded 791 mg of the title compound (99% yield).

Workup

  1. extractionThe aqueous reaction mixture was extracted with dichloromethane
  2. dry with materialThe combined organic phase was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated at reduced pressure
  5. customPurification by chromatography (silica gel, 0-20% methanol in dichloromethane)

Sources & evidence

ORD record
ord-2bd343301a104a76b3c1f9c82d82b970
Source dataset
uspto-grants-2014_01
Patent number
US08629148B2

Reaction notes

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