Diethyl Malonate → 2-{5-[2-(4-Acetylamino-phenylsulfanyl)-5-methyl-phenylamino]-[1,8]naphthyridin-2-yl}-malonic acid diethyl ester

HRID 883883Notes

Reaction equation

HRID 883883 reaction equation
[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].Cl[C:15]1[N:24]=[C:23]2[C:18]([C:19]([NH:25][C:26]3[CH:31]=[C:30]([CH3:32])[CH:29]=[CH:28][C:27]=3[S:33][C:34]3[CH:39]=[CH:38][C:37]([NH:40][C:41](=[O:43])[CH3:42])=[CH:36][CH:35]=3)=[CH:20][CH:21]=[N:22]2)=[CH:17][CH:16]=1>C1COCC1>[CH2:12]([O:11][C:3](=[O:10])[CH:4]([C:15]1[CH:16]=[CH:17][C:18]2[C:23](=[N:22][CH:21]=[CH:20][C:19]=2[NH:25][C:26]2[CH:31]=[C:30]([CH3:32])[CH:29]=[CH:28][C:27]=2[S:33][C:34]2[CH:39]=[CH:38][C:37]([NH:40][C:41](=[O:43])[CH3:42])=[CH:36][CH:35]=2)[N:24]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH3:13]

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 86615485N-{4-[2-(7-Chloro-[1,8]naphthyridin-4-ylamino)-4-methyl-phenylsulfanyl]-phenyl}-acetamide

Product 1

HCID 672508532-{5-[2-(4-Acetylamino-phenylsulfanyl)-5-methyl-phenylamino]-[1,8]naphthyridin-2-yl}-malonic acid diethyl esterYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a slurry of sodium hydride (95%, 0.045 g, 1.8 mmol) in 10 mL anhydrous THF at 0° C. under an atmosphere of N2 was added diethyl malonate (0.32 g, 2.0 mmol) dropwise. The mixture was stirred for 30 minutes at ambient temperature, treated with the product from Example 23a (0.141 g, 0.3 mmol), heated at 110° C. for two hours, cooled and partitioned between EtOAc and water. The ethyl acetate layer was washed with saturated brine, dried over sodium sulfate, filtered and concentrated giving the title compound as a yellow glass, (0.14 g, 84% yield).

Workup

  1. temperatureheated at 110° C. for two hours
  2. temperaturecooled
  3. custompartitioned between EtOAc and water
  4. washThe ethyl acetate layer was washed with saturated brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-2a213fc6d9d34945ba2df2ec8b630909
Source dataset
uspto-grants-2012_08
Patent number
US08236950B2

Reaction notes

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