Ammonia → (4-Methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)methanamine

HRID 475096Notes

Reaction equation

HRID 475096 reaction equation
[CH3:1][O:2][C:3]1[C:11]2[N:10]=[CH:9][N:8]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[C:7]=2[CH:6]=[CH:5][C:4]=1[CH:18]=[N:19]O.N>CO.[Ni]>[CH3:1][O:2][C:3]1[C:11]2[N:10]=[CH:9][N:8]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[C:7]=2[CH:6]=[CH:5][C:4]=1[CH2:18][NH2:19]

Participants

5

Reactant 2

HCID 222AmmoniaHCID 866946914-methoxy-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole-5-carbaldehyde oxime

Product 1

HCID 71272221(4-Methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)methanamineYield 58.9%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 887MethanolSolvent

Procedure

A 1 L autoclave was cooled under a stream of nitrogen and charged with 4-methoxy-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole-5-carbaldehyde oxime (14.50 g, 0.052 mol, 1.0 equiv.) and aqueous ammonia (30 mL) in MeOH (300 mL). To this was added Raney Nickel (15.0 g, w/w) and the reaction was stirred at RT under hydrogen (pressure ˜60 psi) overnight. The reaction mixture was then filtered through a Celite® pad and the filtrate was concentrated in vacuo. The crude material was purified by neutral alumina column chromatography using a MeOH/DCM gradient (5 to 10% MeOH to afford (4-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)methanamine (97, 8.0 g, 57%) as a brown viscous oily liquid.

Workup

  1. temperatureA 1 L autoclave was cooled under a stream of nitrogen
  2. filtrationThe reaction mixture was then filtered through a Celite® pad
  3. concentrationthe filtrate was concentrated in vacuo
  4. customThe crude material was purified by neutral alumina column chromatography

Sources & evidence

ORD record
ord-ed08940fdb8e4d60b583242fc5cf1f36
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

Loading…