2-Methylbenzylamine → [5-(5-Methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-(2-methyl-benzyl)-amine

HRID 1915031Notes

Reaction equation

HRID 1915031 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([N:8]2[C:12]3[CH:13]=[CH:14][C:15]([O:17][CH3:18])=[CH:16][C:11]=3[N:10]=[C:9]2[C:19]([F:22])([F:21])[F:20])=[N:6][CH:7]=1.FC1C=CC=C(F)C=1C(NC1C=NC(N2C3C=CC(OC)=CC=3N=C2C(F)(F)F)=CN=1)=O.[CH3:55][C:56]1[CH:63]=[CH:62][CH:61]=[CH:60][C:57]=1[CH2:58][NH2:59].N1CCC[C@H]1C(O)=O>CS(C)=O.[Cu]I.CCOC(C)=O>[CH3:18][O:17][C:15]1[CH:14]=[CH:13][C:12]2[N:8]([C:5]3[N:6]=[CH:7][C:2]([NH:59][CH2:58][C:57]4[CH:60]=[CH:61][CH:62]=[CH:63][C:56]=4[CH3:55])=[N:3][CH:4]=3)[C:9]([C:19]([F:22])([F:21])[F:20])=[N:10][C:11]=2[CH:16]=1

Participants

8

Reactant 4

HCID 69932-MethylbenzylamineHCID 145742L-ProlineHCID 247517822,6-difluoro-N-[5-(5-methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-benzamideHCID 573569041-(5-Bromopyrazin-2-YL)-2-(trifluoromethyl)-5-methoxy-1H-benzo[D]imidazole

Product 1

HCID 24752641[5-(5-Methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-(2-methyl-benzyl)-amineYield 46.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Into a 50 mL roundbottom flask, was placed a solution of 1-(5-bromo-pyrazin-2-yl)-5-methoxy-2-trifluoromethyl-1H-benzoimidazole (iv) (50 mg, 0.13 mmol) in DMSO (5 mL) (1-(5-bromo-pyrazin-2-yl)-5-methoxy-2-trifluoromethyl-1H-benzoimidazole (iv) was prepared as described for Compound 1 above). To this was added 2-methyl-benzylamine (40 mg, 0.33 mmol) followed by CuI (10 mg, 0.05 mmol). To the mixture was added L-proline (20 mg, 0.17 mmol). The resulting solution was held at 50° C. for 1 hr while the reaction progress was monitored by TLC (EtOAc/PE=1:2). After completion, the reaction mixture was allowed to cool to room temperature, then washed twice with H2O (30 mL each). After removal of the volatile components under vacuum, the residue was purified by eluting through a silica gel column with a 1:10 EtOAc/PE solvent system. This resulted in 25 mg (44%) of the product [5-(5-Methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-(2-methyl-benzyl)-amine (Compound 46) as a white solid.

Workup

  1. customInto a 50 mL roundbottom flask, was placed
  2. washwashed twice with H2O (30 mL each)
  3. customAfter removal of the volatile components under vacuum
  4. customthe residue was purified
  5. washby eluting through a silica gel column with a 1:10 EtOAc/PE solvent system

Sources & evidence

ORD record
ord-f0ebc9a4139a4afa8c05400f8f8d5693
Source dataset
uspto-grants-2013_12
Patent number
US08614321B2

Reaction notes

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