Methylamine → 6-Methyl-2-(3-methylaminomethyl-phenoxy)-nicotinonitrile fumarate

HRID 1178513Notes

Reaction equation

HRID 1178513 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([CH:16]=[CH:17][CH:18]=1)[O:6][C:7]1[N:14]=[C:13]([CH3:15])[CH:12]=[CH:11][C:8]=1[C:9]#[N:10])=O.CN.[C:21]([BH3-])#[N:22].[Na+].[C:25]([OH:32])(=[O:31])/[CH:26]=[CH:27]/[C:28]([OH:30])=[O:29]>C(O)(=O)C.CO>[C:25]([OH:32])(=[O:31])/[CH:26]=[CH:27]/[C:28]([OH:30])=[O:29].[CH3:15][C:13]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[C:7]([O:6][C:5]2[CH:16]=[CH:17][CH:18]=[C:3]([CH2:1][NH:22][CH3:21])[CH:4]=2)[N:14]=1

Participants

6

Reactant 4

HCID 6329MethylamineHCID 444972Fumaric AcidHCID 5003444Sodium cyanoborohydrideHCID 219304312-(3-Formyl-phenoxy)-6-methyl-nicotinonitrile

Product 1

HCID 219304146-Methyl-2-(3-methylaminomethyl-phenoxy)-nicotinonitrile fumarateYield 56.8%

Reagents, catalysts & solvents 1

HCID 10129899Acetic acid methanolSolvent

Procedure

2-(3-Formyl-phenoxy)-6-methyl-nicotinonitrile (0.77 g, 3.2 mmol), methylamine (2M in methanol, 7.0 mL, 14 mmol) and sodium cyanoborohydride (250 mg, 4.0 mmol) were s stirred at ambient temperature in a 1% acetic acid/methanol solution (100 mL) for 20 h. The solvent was removed in vacuo. The residue was treated with 10% sodium carbonate solution and extracted with ethyl acetate. The ethyl acetate layer was separated and fumaric acid (0.36 g, 3.1 mmol) was added. After the solvent was removed in vacuo, the residue was triturated with ethyl acetate overnight, collected by filtration, and dried to give 6-methyl-2-(3-methylaminomethyl-phenoxy)-nicotinonitrile fumarate (650 mg, 55%) as an off-white solid.

Workup

  1. customThe solvent was removed in vacuo
  2. additionThe residue was treated with 10% sodium carbonate solution
  3. extractionextracted with ethyl acetate
  4. customThe ethyl acetate layer was separated
  5. customAfter the solvent was removed in vacuo
  6. customthe residue was triturated with ethyl acetate overnight
  7. filtrationcollected by filtration
  8. customdried

Sources & evidence

ORD record
ord-f857015e7adc4ea1a54cf1eba7aa8242
Source dataset
uspto-grants-2007_10
Patent number
US07276528B2

Reaction notes

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