Methylamine → (+/-)-N-methyl-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)ethanamine

HRID 475203Notes

Reaction equation

HRID 475203 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[C:11]2[CH:12]=[CH:13][C:14]([C:16](=O)[CH3:17])=[CH:15][C:10]=2[N:9]=[CH:8]1.[BH4-].[Na+].[CH3:21][NH2:22]>CO>[CH3:21][NH:22][CH:16]([C:14]1[CH:13]=[CH:12][C:11]2[N:7]([CH:2]3[CH2:3][CH2:4][CH2:5][CH2:6][O:1]3)[CH:8]=[N:9][C:10]=2[CH:15]=1)[CH3:17]

Participants

5

Reactant 3

HCID 6329MethylamineHCID 4311764Sodium borohydrideHCID 712726001-(1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)ethanone

Product 1

HCID 71272528(+/-)-N-methyl-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)ethanamineYield 15%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 82 (1.2 g, 4.9 mmol) in 30% methanamine in MeOH (50 mL) was stirred at RT for 15 h. To the reaction mixture was added NaBH4 (186 mg, 4.9 mmol) at RT in several portions and stirred overnight. The reaction mixture was concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with DCM/MeOH (100:1) followed by reverse phase chromatography on CombiFlash® eluting with 0.01% NH4OH ammonia in water (solvent A) and MeCN (solvent B) to afford 200 mg (15%) of (±)-N-methyl-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)ethanamine (84) as yellow oil: MS (ESI) m/z=260.3 (M+1).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customThe crude product was purified by SiO2 chromatography
  3. washeluting with DCM/MeOH (100:1)
  4. washeluting with 0.01% NH4OH ammonia in water (solvent A) and MeCN (solvent B)

Sources & evidence

ORD record
ord-6dfa9aed3ce44ea5b3a6d3a72893a085
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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