Piperidine → HCID 178480510, compound

HRID 2404481Notes

Reaction equation

HRID 2404481 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:10]([O:19][CH:20]1[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]1)[C:11]1[CH:12]=[C:13]([CH:16]=[CH:17][CH:18]=1)[CH:14]=O.[NH:27]1[CH2:33][C:31](=[O:32])[NH:30][C:28]1=S.[NH:34]1CCCCC1>C(O)C.O>[NH:3]1[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:1]=[C:2]1[CH:10]([O:19][CH:20]1[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]1)[C:11]1[CH:12]=[C:13]([CH:16]=[CH:17][CH:18]=1)[CH:14]=[C:33]1[NH:27][C:28](=[NH:34])[NH:30][C:31]1=[O:32]

Participants

5

Reactant 3

HCID 8082PiperidineHCID 12740302-ThiohydantoinHCID 86695327HCID 86695327, compound

Product 1

HCID 178480510HCID 178480510, compound

Reagents, catalysts & solvents 1

HCID 19096565Water ethanolSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of 3-[(1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]benzaldehyde (example 505C, 200 mg) in a mixture of ethanol-water (8:2) (3 mL) is added thiohydantoin (70 mg) and piperidine (57 μL). The reaction mixture is heated at 55° C. for 5 h. Ethanol is removed under reduced pressure. Water is added and the reaction mixture is extracted by ethyl acetate. The organic phase is washed by water, then dried over magnesium sulfate and concentrated. The residue is purified by chromatography on silica gel (gradient dichloromethane/methanol from 95/5 to 90/10). The residue is dissolved in methanol (6 mL) and 30% solution of aqueous ammonia (1.1 mL) and tert-butylhydroperoxide (90 μL) are added. The reaction mixture is stirred at room temperature for two days. The reaction mixture is evaporated to dryness. The residue is purified by chromatography on silica gel (gradient dichloromethane/methanol/ammonia from 90/10/0.1 to 70/30/0.1) to give 5-{3-[(1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]benzylidene}-2-iminoimidazolidin-4-one. MS, [M+H]+=431.1; [M+Na]+=453.1

Workup

  1. customEthanol is removed under reduced pressure
  2. additionWater is added
  3. extractionthe reaction mixture is extracted by ethyl acetate
  4. washThe organic phase is washed by water
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue is purified by chromatography on silica gel (gradient dichloromethane/methanol from 95/5 to 90/10)
  8. dissolutionThe residue is dissolved in methanol (6 mL)
  9. addition30% solution of aqueous ammonia (1.1 mL) and tert-butylhydroperoxide (90 μL) are added
  10. customThe reaction mixture is evaporated to dryness
  11. customThe residue is purified by chromatography on silica gel (gradient dichloromethane/methanol/ammonia from 90/10/0.1 to 70/30/0.1)

Sources & evidence

ORD record
ord-a9550c26e3064d06a18056ec7414e9d4
Source dataset
uspto-grants-2014_08
Patent number
US08802664B2

Reaction notes

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