Sodium hydride → Methyl 3-methyl-2-oxo-1-(2-pyridinylmethyl)-4-imidazolidinecarboxylate

HRID 2080959Notes

Reaction equation

HRID 2080959 reaction equation
[H-].[Na+].[CH3:3][N:4]1[CH:8]([C:9]([O:11][CH3:12])=[O:10])[CH2:7][NH:6][C:5]1=[O:13].Br.Br[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1>CN1CCCC1=O>[CH3:3][N:4]1[CH:8]([C:9]([O:11][CH3:12])=[O:10])[CH2:7][N:6]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[C:5]1=[O:13]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27347202-(Bromomethyl)pyridine hydrobromideHCID 67103585Methyl 3-methyl-2-oxo-4-imidazolidinecarboxylate

Product 1

HCID 67103569Methyl 3-methyl-2-oxo-1-(2-pyridinylmethyl)-4-imidazolidinecarboxylateYield 25.4%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of sodium hydride (240 mg, 6 mmol, 60% dispersion in oil) in N-methyl-2-pyrrolidinone (6 ml) was stirred at 0° C. under argon. A solution of methyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (474 mg, 3 mmol) (prepared as described in step (ii) of Example 8) in N-methyl-2-pyrrolidinone (3 ml) was added dropwise over 10 minutes. The reaction was stirred at 0° C. for 15 minutes and 2-(bromomethyl)pyridine hydrobromide (835 mg, 3.3 mmol) was added portionwise over 5 minutes. The mixture was stirred at 0° C. for 30 minutes and then at room temperature for 20 hours. The reaction was treated with ice water and extracted with dichloromethane. The mixture was applied to a SCX ion exchange cartridge and washed with methanol and then 2M ammonia in methanol. The basic fractions were combined and evaporated. The residue was purified by silica gel chromatography eluting with 0-10% methanol in dichloromethane to give methyl 3-methyl-2-oxo-1-(2-pyridinylmethyl)-4-imidazolidinecarboxylate (190 mg), LC/MS [M+H]+=250. (ii) A stirred solution of methyl 3-methyl-2-oxo-1-(2-pyridinylmethyl)-4-imidazolidinecarboxylate (190 mg, 0.76 mmol) in tetrahydrofuran (1.5 ml)/water (1 ml) at 0° C. was treated with lithium hydroxide (55 mg, 2.28 mmol) and the reaction mixture was stirred at 0-5° C. for 3 hours. The reaction was acidified to pH 2 with 2N hydrochloric acid and the solvent was evaporated. The residue was dried to give 3-methyl-2-oxo-1-(2-pyridinylmethyl)-4-imidazolidinecarboxylic acid which was used crude in the next step.

Workup

  1. stirringThe reaction was stirred at 0° C. for 15 minutes
  2. stirringThe mixture was stirred at 0° C. for 30 minutes
  3. extractionextracted with dichloromethane
  4. washwashed with methanol
  5. customevaporated
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-fcd24a740633481a892b1a07513ea366
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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