Methanol → Methyl 4-(3-amino-6-(4-(benzylamino)cyclohexyl)pyrazin-2-yl)-2-fluorobenzoate

HRID 596048Notes

Reaction equation

HRID 596048 reaction equation
[NH2:1][C:2]1[C:3]([C:15]2[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[C:17]([F:25])[CH:16]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]2)=[CH:6][N:7]=1.CO.[C:28]1([CH2:34][NH2:35])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[BH4-].[Na+]>C(OCC)(=O)C>[NH2:1][C:2]1[C:3]([C:15]2[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[C:17]([F:25])[CH:16]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][CH:11]([NH:35][CH2:34][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:10][CH2:9]2)=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 7504BenzylamineHCID 4311764Sodium borohydrideHCID 118045808Methyl 4-(3-amino-6-(4-oxocyclohexyl)pyrazin-2-yl)-2-fluorobenzoate

Product 1

HCID 118045264Methyl 4-(3-amino-6-(4-(benzylamino)cyclohexyl)pyrazin-2-yl)-2-fluorobenzoateYield 92.7%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To methyl 4-(3-amino-6-(4-oxocyclohexyl)pyrazin-2-yl)-2-fluorobenzoate (300 mg, 0.874 mmol) was added MeOH (4 mL), phenylmethanamine (112 mg, 1.048 mmol) and last dry 4 Å molecular sieves. The reaction was stirred at room temperature for 16 h. Then NaBH4 (165 mg, 4.37 mmol) was added and stirred at room temperature for 2 h followed by LCMS. To the reaction was added 150 mL of ethyl acetate, washed with saturated sodium bicarbonate, water (2×), saturated salt solution, dried over sodium sulfate, filtered and concentrated to residue to give 352 mg of the desired product in 2:1 trans to cis ratio, used as is (93%). LCMS (m/z): 435.3 (MH+), 0.68 min and 0.72 min.

Workup

  1. customlast dry 4 Å molecular sieves
  2. stirringstirred at room temperature for 2 h
  3. washwashed with saturated sodium bicarbonate, water (2×), saturated salt solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to residue

Sources & evidence

ORD record
ord-74b0142df94540328ff745a8a3d49bb1
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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