Isopropyl iodide → 3-Methyl-1-(1-methylethyl)-4-({1-[3-(trifluoromethyl)phenyl]-1H-tetrazol-5-yl}methyl)-2-piperazinone

HRID 517769Notes

Reaction equation

HRID 517769 reaction equation
[CH3:1][CH:2]1[N:7]([CH2:8][C:9]2[N:13]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=3)[N:12]=[N:11][N:10]=2)[CH2:6][CH2:5][NH:4][C:3]1=[O:24].I[CH:26]([CH3:28])[CH3:27].[H-].[Na+]>CN(C)C=O.C(OCC)(=O)C>[CH3:1][CH:2]1[N:7]([CH2:8][C:9]2[N:13]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=3)[N:12]=[N:11][N:10]=2)[CH2:6][CH2:5][N:4]([CH:26]([CH3:28])[CH3:27])[C:3]1=[O:24]

Participants

6

Reactant 3

HCID 6362Isopropyl iodide2×HCID 24758Sodium hydride2×HCID 566001413-Methyl-4-({1-[3-(trifluoromethyl)phenyl]-1H-tetrazol-5-yl}methyl)-2-piperazinone2×

Product 1

HCID 566001393-Methyl-1-(1-methylethyl)-4-({1-[3-(trifluoromethyl)phenyl]-1H-tetrazol-5-yl}methyl)-2-piperazinoneYield 9.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-methyl-4-({1-[3-(trifluoromethyl)phenyl]-1H-tetrazol-5-yl}methyl)-2-piperazinone (75 mg, 0.220 mmol, Compound 32), in N,N-Dimethylformamide (DMF) (1 mL) was added 2-iodopropane (0.024 mL, 0.242 mmol) and sodium hydride (8.81 mg, 0.220 mmol). The resulting reaction mixture was stirred at room temperature for 24 hours. To the reaction mixture was added 1 equivalent of 2-iodopropane and 0.5 equivalent of sodium hydride and stirred for an additional 24 h at room temperature. The reaction mixture was diluted with ethyl acetate (20 mL) and washed with 2N NaOH solution (10 mL). The aqueous phase was extracted with ethyl acetate (2×10 mL). All of the organic phases were combined, dried over magnesium sulphate, filtered and concentrated. The crude product was purified by MDAP. The relevant fractions were combined, concentrated and dried to give the title compound as a colourless oil (8 mg).

Workup

  1. customThe resulting reaction mixture
  2. stirringstirred for an additional 24 h at room temperature
  3. washwashed with 2N NaOH solution (10 mL)
  4. extractionThe aqueous phase was extracted with ethyl acetate (2×10 mL)
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by MDAP
  9. concentrationconcentrated
  10. customdried

Sources & evidence

ORD record
ord-f6ba4a87b1424f01ac51c6c7eb494db7
Source dataset
uspto-grants-2015_08
Patent number
US09115132B2

Reaction notes

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