Triethylamine → 4-Chloro-5-fluoro-2-[[(1R)-3-[[(5-methylpyrazinyl)methyl]amino]-1-phenylpropyl]oxy]benzonitrile dihydrochloride

HRID 2179949Notes

Reaction equation

HRID 2179949 reaction equation
[Cl:1][C:2]1[C:9]([F:10])=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:11][C@@H:12]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:13][CH2:14]I)[CH:3]=1.[CH3:22][C:23]1[N:24]=[CH:25][C:26]([CH2:29][NH2:30])=[N:27][CH:28]=1.C(N(CC)CC)C>CS(C)=O>[ClH:1].[ClH:1].[Cl:1][C:2]1[C:9]([F:10])=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:11][C@@H:12]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:13][CH2:14][NH:30][CH2:29][C:26]2[CH:25]=[N:24][C:23]([CH3:22])=[CH:28][N:27]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27564962-(Aminomethyl)-5-methylpyrazineHCID 697986504-Chloro-5-fluoro-2-{[(1R)-3-iodo-1-phenylpropyl]oxy}benzonitrile

Product 1

HCID 698019914-Chloro-5-fluoro-2-[[(1R)-3-[[(5-methylpyrazinyl)methyl]amino]-1-phenylpropyl]oxy]benzonitrile dihydrochloride

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

4-Chloro-5-fluoro-2-{[(1R)-3-iodo-1-phenylpropyl]oxy}benzonitrile (200 mg, 0.48 mmol), 5-methyl-2-pyrazinemethanamine (120 mg, 0.96 mmol) and triethylamine (335 μl, 2.4 mmol) were stirred in DMSO (5 ml) for 48 h. The mixture was washed with water and purified by chromatography (5% 1M ammonia-methanol/dichloromethane). The eluent was evaporated and the residue treated with 4M hydrogen chloride in dioxan (5 ml). The solvent was evaporated, azeotroped twice with toluene and triturated with ether to give the required product as a white solid.

Workup

  1. washThe mixture was washed with water
  2. custompurified by chromatography (5% 1M ammonia-methanol/dichloromethane)
  3. customThe eluent was evaporated
  4. additionthe residue treated with 4M hydrogen chloride in dioxan (5 ml)
  5. customThe solvent was evaporated
  6. customazeotroped twice with toluene
  7. customtriturated with ether

Sources & evidence

ORD record
ord-2fd60212d7424e4991420f898643035b
Source dataset
uspto-grants-2005_05
Patent number
US06887871B2

Reaction notes

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