Diethyl methylmalonate → HCID 68460666, compound

HRID 2197825Notes

Reaction equation

HRID 2197825 reaction equation
[H-].[Na+].C(O[C:6](=O)[CH:7]([CH3:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9])C.ClC1[N:25]=[C:24]2[C:19]([C:20]([NH:26][C:27]3[CH:32]=[C:31]([CH3:33])[CH:30]=[CH:29][C:28]=3[S:34][C:35]3[CH:40]=[CH:39][C:38]([NH:41][C:42](=[O:44])[CH3:43])=[CH:37][CH:36]=3)=[CH:21][CH:22]=[N:23]2)=[CH:18][CH:17]=1>C1COCC1>[CH2:11]([O:10][C:8](=[O:9])[CH:7]([C:6]1[CH:17]=[CH:18][C:19]2[C:24](=[N:23][CH:22]=[CH:21][C:20]=2[NH:26][C:27]2[CH:32]=[C:31]([CH3:33])[CH:30]=[CH:29][C:28]=2[S:34][C:35]2[CH:40]=[CH:39][C:38]([NH:41][C:42](=[O:44])[CH3:43])=[CH:37][CH:36]=2)[N:25]=1)[CH3:13])[CH3:12]

Participants

5

Reactant 3

HCID 11857Diethyl methylmalonateHCID 24758Sodium hydrideHCID 86615485N-{4-[2-(7-Chloro-[1,8]naphthyridin-4-ylamino)-4-methyl-phenylsulfanyl]-phenyl}-acetamide

Product 1

HCID 68460666HCID 68460666, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a slurry of sodium hydride (95%, 0.025 g, 1.0 mmol) in 5 mL anhydrous THF at 0° C. under an atmosphere of N2 was added 2-methyl-malonic acid diethyl ester (0.174 g, 1.0 mmol) dropwise. The mixture was stirred for 30 minutes at ambient temperature, treated with the product from Example 24a (0.047 g, 1.0 mmol), microwave at 120° C. for 1 hour, cooled, partitioned between ethyl acetate and water and neutralized with 1M HCl. The aqueous layer was extracted by ethyl acetate and the combined organic layers were dried over Na2SO4, filtered and concentrated under vacuum giving the crude title compound. The residue was purified by chromatography on silica eluting with 1% methanol in dichloromethane to give the title compound (0.031 g, 62%). 1H NMR (300 MHz, DMSO-D6) δ ppm 1.14 (t, J=7.17 Hz, 3H) 1.52 (d, J=7.35 Hz, 3H) 2.04 (s, 3H) 2.30 (s, 3H) 4.10 (m, 3H) 6.17 (s, br, 1H) 7.04 (m, 3H) 7.26 (d, J=8.82 Hz, 2H) 7.48 (d, J=7.35 Hz, 1H) 7.57 (d, J=8.46 Hz, 2H) 8.45 (d, J=8.46 Hz, 1H) 8.78 (d, J=8.82 Hz, 1H) 9.11 (s, 1H) 10.05 (s, 1H); (ESI+) m/z 501 (M+H)+.

Workup

  1. temperaturecooled
  2. custompartitioned between ethyl acetate and water and neutralized with 1M HCl
  3. extractionThe aqueous layer was extracted by ethyl acetate
  4. dry with materialthe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customgiving the crude title compound
  8. customThe residue was purified by chromatography on silica eluting with 1% methanol in dichloromethane

Sources & evidence

ORD record
ord-6e5d57ed4b664378a6ad6fc2179494ae
Source dataset
uspto-grants-2012_12
Patent number
US08338605B2

Reaction notes

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