Benzylamine → N'-Benzyl-4-(4-fluorobenzyl)-3-oxopiperazine-1-carboximidamide

HRID 1162806Notes

Reaction equation

HRID 1162806 reaction equation
[F:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][N:10]([C:13]#[N:14])[CH2:9][C:8]2=[O:15])=[CH:4][CH:3]=1.[CH2:18]([NH2:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C(O)(C(F)(F)F)C(F)(F)F>[CH2:18]([N:25]=[C:13]([N:10]1[CH2:11][CH2:12][N:7]([CH2:6][C:5]2[CH:16]=[CH:17][C:2]([F:1])=[CH:3][CH:4]=2)[C:8](=[O:15])[CH2:9]1)[NH2:14])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

4

Reactant 2

HCID 7504BenzylamineHCID 860749504-(4-Fluorobenzyl)-3-oxopiperazine-1-carbonitrile

Product 1

HCID 68432646N'-Benzyl-4-(4-fluorobenzyl)-3-oxopiperazine-1-carboximidamide

Reagents, catalysts & solvents 1

HCID 135291,1,1,3,3,3-Hexafluoro-2-propanolSolvent

Procedure

A solution of 4-(4-fluorobenzyl)-3-oxopiperazine-1-carbonitrile (0.56 g, 2.40 mmol) and benzylamine (0.53 mL, 4.80 mmol) in 1,1,1,3,3,3-hexafluoroisopropanol (10 mL) was heated to reflux overnight. The solvent was removed in vacuo and the residue was purified by prep HPLC on a C18 column eluting with a water/acetonitrile/TFA gradient. The pure fractions were concentrated to an oil. The oil was partitioned between aqueous sat. NH4Cl and chloroform. The layers were separated and the aqueous layer was extracted twice more with chloroform. The combined organic extracts were dried over Na2SO4, filtered, and concentrated to give an oil for the title compound. 1H NMR (400 MHz, d6 DMSO) before work-up δ 8.29 (t, 1H, J=5.5 Hz), 7.81 (bs, 2H), 7.29-7.40 (m, 7H), 7.19 (t, 2H, J=8.8 Hz), 4.56 (s, 2H), 4.45 (d, 2H, J=5.7 Hz), 4.15 (s, 2H), 3.67 (m, 2H), and 3.39 (m, 2H). ES MS (M+1)=341.3.

Workup

  1. temperatureto reflux overnight
  2. customThe solvent was removed in vacuo
  3. customthe residue was purified by prep HPLC on a C18 column
  4. washeluting with a water/acetonitrile/TFA gradient
  5. concentrationThe pure fractions were concentrated to an oil
  6. customThe oil was partitioned between aqueous sat. NH4Cl and chloroform
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted twice more with chloroform
  9. dry with materialThe combined organic extracts were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-f7a06cfcd9f64eaeab222f1afa4357b2
Source dataset
uspto-grants-2010_10
Patent number
US07820680B2

Reaction notes

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