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

HRID 1178500Notes

Reaction equation

HRID 1178500 reaction equation
[CH:1]([C:3]1[C:4]([O:22][CH3:23])=[C:5]([CH:19]=[CH:20][CH:21]=1)[O:6][C:7]1[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:8]=1[C:9]#[N:10])=O.CN.[C:26]([BH3-])#[N:27].[Na+].[C:30]([OH:37])(=[O:36])/[CH:31]=[CH:32]/[C:33]([OH:35])=[O:34]>C(O)(=O)C.CO>[C:30]([OH:37])(=[O:36])/[CH:31]=[CH:32]/[C:33]([OH:35])=[O:34].[CH3:23][O:22][C:4]1[C:3]([CH2:1][NH:27][CH3:26])=[CH:21][CH:20]=[CH:19][C:5]=1[O:6][C:7]1[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:8]=1[C:9]#[N:10]

Participants

6

Reactant 4

HCID 6329MethylamineHCID 444972Fumaric AcidHCID 5003444Sodium cyanoborohydrideHCID 219303952-(3-Formyl-2-methoxyphenoxy)-6-(trifluoromethyl)nicotinonitrile

Product 1

HCID 219303492-(2-Methoxy-3-methylaminomethyl-phenoxy)-6-trifluoromethyl-nicotinonitrile fumarateYield 67%

Reagents, catalysts & solvents 1

HCID 10129899Acetic acid methanolSolvent

Procedure

2-(3-Formyl-2-methoxyphenoxy)-6-(trifluoromethyl)nicotinonitrile (0.50 g, 1.6 mmol), methylamine (33% in ethanol, 0.9 mL, 7.2 mmol) and sodium cyanoborohydride (120 mg, 1.9 mmol) were stirred at ambient temperature in a 1% acetic acid/methanol solution (80 mL) for 18 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 (0.20 g, 1.7 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 2-(2-methoxy-3-methylaminomethyl-phenoxy)-6-trifluoromethyl-nicotinonitrile fumarate (468 mg, 67%) as a 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-0749a941fa6f4ffd9c77823cb2d58fd2
Source dataset
uspto-grants-2007_10
Patent number
US07276528B2

Reaction notes

Loading…