Ethylmorpholine → N-{[4-fluoro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-4-imidazolidinecarboxamide

HRID 2081044Notes

Reaction equation

HRID 2081044 reaction equation
[CH3:1][N:2]1[CH:6]([C:7]([OH:9])=O)[CH2:5][NH:4][C:3]1=[O:10].CN1C(C(OC(C)(C)C)=O)CNC1=O.O=C1N(C(OCC2C=CC=CC=2)=O)[C@H](C(O)=O)CN1.C(N1CCOCC1)C.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[F:75][C:76]1[CH:81]=[CH:80][C:79]([CH2:82][NH2:83])=[CH:78][C:77]=1[C:84]([F:87])([F:86])[F:85]>ClCCl>[F:75][C:76]1[CH:81]=[CH:80][C:79]([CH2:82][NH:83][C:7]([CH:6]2[CH2:5][NH:4][C:3](=[O:10])[N:2]2[CH3:1])=[O:9])=[CH:78][C:77]=1[C:84]([F:85])([F:86])[F:87]

Participants

9

Reactant 7

HCID 7525EthylmorpholineHCID 522270[4-Fluoro-3-(trifluoromethyl)phenyl]methanamineHCID 688196(S)-(-)-2-Oxo-1,5-imidazolidinedicarboxylic acid 1-benzyl esterHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 553001513-Methyl-2-oxoimidazolidine-4-carboxylic acidHCID 671035641,1-Dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate

Product 1

HCID 59252104N-{[4-fluoro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-4-imidazolidinecarboxamideYield 4.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 3-methyl-2-oxo-4-imidazolidinecarboxylic acid (86 mg, 0.6 mmol) (prepared as described in Example 28 from 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate, itself prepared as described in step (iii) of Example 13, starting originally from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid), N-ethyl morpholine (0.380 ml, 3.00 mmol), 1-hydroxybenzotriazole hydrate (110 mg, 0.720 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (138 mg, 0.720 mmol) in dichloromethane (9 ml) was stirred at room temperature for 10 minutes, under an argon atmosphere. {[4-Fluoro-3-(trifluoromethyl)phenyl]methyl}amine (127 mg, 0.660 mmol) was added and the reaction was stirred overnight under an argon atmosphere. The reaction mixture was diluted with dichloromethane (10 ml) and the solution was washed with saturated sodium hydrogen carbonate solution (10 ml), water (10 ml) and brine (10 ml). The organic solution was dried and the solvent was evaporated in vacuo. The residue was purified by mass-directed automated HPLC. Fractions containing product were collected and the solvent was evaporated in vacuo to give N-{[4-fluoro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-4-imidazolidinecarboxamide (8 mg, 4% yield) as a white solid. LC/MS [M+H]+=320, retention time=1.87 minutes.

Workup

  1. customprepared
  2. customprepared
  3. stirringthe reaction was stirred overnight under an argon atmosphere
  4. washthe solution was washed with saturated sodium hydrogen carbonate solution (10 ml), water (10 ml) and brine (10 ml)
  5. customThe organic solution was dried
  6. customthe solvent was evaporated in vacuo
  7. customThe residue was purified
  8. additionFractions containing product
  9. customwere collected
  10. customthe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-bc58f31f31e14eaa9fb76fb6405eac77
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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