N-Hydroxyacetamidine → (4-Benzyl-6-methyl-pyrimidin-2-yl)-[1-(3-methyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yl]-amine

HRID 451437Notes

Reaction equation

HRID 451437 reaction equation
[CH2:1]([C:8]1[CH:13]=[C:12]([CH3:14])[N:11]=[C:10]([NH:15][CH:16]2[CH2:21][CH2:20][N:19]([C:22]#[N:23])[CH2:18][CH2:17]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:24](=[N:27][OH:28])(N)[CH3:25]>CCOC(C)=O.C1COCC1.O.[Cl-].[Zn+2].[Cl-]>[CH2:1]([C:8]1[CH:13]=[C:12]([CH3:14])[N:11]=[C:10]([NH:15][CH:16]2[CH2:21][CH2:20][N:19]([C:22]3[O:28][N:27]=[C:24]([CH3:25])[N:23]=3)[CH2:18][CH2:17]2)[N:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 2

HCID 30926N-HydroxyacetamidineHCID 86656706HCID 86656706, compound

Product 1

HCID 53353625(4-Benzyl-6-methyl-pyrimidin-2-yl)-[1-(3-methyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yl]-amine

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 4-(4-benzyl-6-methyl-pyrimidin-2-ylamino)-piperidine-1-carbonitrile (135 mg, 0.44 mmol) and acetamidoxime (39 mg, 0.53 mmol) in EtOAc (1 mL) and THF (1 mL) was added within 10 minutes a solution of zinc chloride (73 mg, 0.53 mmol) in EtOAc (1 mL). After stirring at room temperature for 4 hours the reaction was heated to reflux over night under nitrogen. The reaction was diluted with water and extracted twice with ethyl acetate. The combined organic layers were washed with saturated aqueous NaCl solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using CH2Cl2/MeOH 19:1 (v/v) as eluent. The title compound was obtained as a colorless gum (98 mg, 61%).

Workup

  1. temperaturewas heated
  2. temperatureto reflux over night under nitrogen
  3. extractionextracted twice with ethyl acetate
  4. washThe combined organic layers were washed with saturated aqueous NaCl solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-d162ee9bccd245ec87a09bd77827bfd2
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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