tert-Butyl ethyl malonate → HCID 57976104, compound

HRID 1865194Notes

Reaction equation

HRID 1865194 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][CH:8]([NH2:11])[CH2:7][CH2:6]1.[CH2:12]([O:14][C:15](=[O:34])[CH:16]([C:24]1[C:29]([N+:30]([O-:32])=[O:31])=[CH:28][N:27]=[C:26](Cl)[N:25]=1)[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH3:13].C(OC(C)(C)C)(=O)CC(OCC)=O>CCO.CCOC(C)=O>[CH2:12]([O:14][C:15](=[O:34])[CH:16]([C:24]1[C:29]([N+:30]([O-:32])=[O:31])=[CH:28][N:27]=[C:26]([NH:11][CH:8]2[CH2:7][CH2:6][N:5]([CH2:4][CH2:3][O:2][CH3:1])[CH2:10][CH2:9]2)[N:25]=1)[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH3:13]

Participants

6

Reactant 3

HCID 96345tert-Butyl ethyl malonateHCID 201191211-(2-Methoxyethyl)piperidin-4-amineHCID 57976101HCID 57976101, compound

Product 1

HCID 57976104HCID 57976104, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To 1-(2-methoxy-ethyl)-piperidin-4-ylamine (4, 1.7 g, 11 mmol) in EtOH (20 mls) was added a solution of the 1:1 mixture of 2-(2-chloro-5-nitro-pyrimidin-4-yl)-malonic acid tert-butyl ester ethyl ester (3) and tert-butyl ethyl malonate (2) (˜5.3 mmol of 3) in EtOH (20 mls) dropwise with stirring. The resulting mixture was stirred at room temperature overnight and then diluted with EtOAc, washed with H2O (1×), sat'd NaCl (1×), dried (Na2SO4), and concentrated in vacuo. The resulting residue was purified by flash chromatography (eluting solvents=CH2Cl2, followed by 2% MeOH in CH2Cl2, followed by 4% MeOH in CH2Cl2) to give 2-{2-[1-(2-methoxy-ethyl)-piperidin-4-ylamino]-5-nitro-pyrimidin-4-yl}-malonic acid tert-butyl ester ethyl ester (5, 733 mgs, 29%). LC/MS Calcd for [M+H]+ 468, found 468.

Workup

  1. stirringThe resulting mixture was stirred at room temperature overnight
  2. washwashed with H2O (1×), sat'd NaCl (1×)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by flash chromatography (eluting solvents=CH2Cl2, followed by 2% MeOH in CH2Cl2, followed by 4% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-72f4af487de845bd933f6aa8f55422c5
Source dataset
uspto-grants-2009_12
Patent number
US07626031B2

Reaction notes

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