Ethyl Acetate → Methyl 4-((3-chloropyrazin-2-yl)(2-cyanoacetamido)methyl)benzoate

HRID 62454Notes

Reaction equation

HRID 62454 reaction equation
[NH2:1][CH:2]([C:13]1[C:18]([Cl:19])=[N:17][CH:16]=[CH:15][N:14]=1)[C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=1.[C:20]([CH2:22][C:23](O)=[O:24])#[N:21].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CC(=O)OCC>C1COCC1>[Cl:19][C:18]1[C:13]([CH:2]([NH:1][C:23](=[O:24])[CH2:22][C:20]#[N:21])[C:3]2[CH:4]=[CH:5][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:11][CH:12]=2)=[N:14][CH:15]=[CH:16][N:17]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 9740Cyanoacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 90303493Methyl 4-(amino(3-chloropyrazin-2-yl)methyl)benzoate

Product 1

HCID 90303780Methyl 4-((3-chloropyrazin-2-yl)(2-cyanoacetamido)methyl)benzoateYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-(amino(3-chloropyrazin-2-yl)methyl)benzoate (54 g, 195 mmol) in THF (500 mL) was added 2-cyanoacetic acid (16.6 g, 195 mmol) and TEA (39.4 g, 390 mmol). The mixture was added HATU (74.1 g, 195 mmol) at 0-5° C., and stirred at room temperature for 1 h. The reaction mixture was extracted with EA and water, the organic layer was dried and concentrated. The residue was purified by column chromatography on silica gel eluted with PE:EA=2:1 to give methyl 4-((3-chloropyrazin-2-yl)(2-cyanoacetamido)methyl)benzoate (67 g, yield 100%).

Workup

  1. extractionThe reaction mixture was extracted with EA and water
  2. customthe organic layer was dried
  3. concentrationconcentrated
  4. customThe residue was purified by column chromatography on silica gel
  5. washeluted with PE

Sources & evidence

ORD record
ord-59b5ecf5a81a4010a58741e1d02b2447
Source dataset
uspto-grants-2016_09
Patent number
US09446130B2

Reaction notes

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