Water → (R)-2-(4-cyano-2,3-difluorophenylamino)-4-methylpentanamide

HRID 2201068Notes

Reaction equation

HRID 2201068 reaction equation
[F:1][C:2]1[C:9]([F:10])=[C:8](F)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].Cl.[NH2:13][C@@H:14]([C:19]([NH2:21])=[O:20])[CH2:15][CH:16]([CH3:18])[CH3:17].CCN(C(C)C)C(C)C.O>CS(C)=O.CCOC(C)=O>[C:4]([C:3]1[CH:6]=[CH:7][C:8]([NH:13][C@H:14]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:19]([NH2:21])=[O:20])=[C:9]([F:10])[C:2]=1[F:1])#[N:5]

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 5189362,3,4-TrifluorobenzonitrileHCID 56776963(R)-2-Amino-4-methylpentanamide hydrochloride

Product 1

HCID 67508536(R)-2-(4-cyano-2,3-difluorophenylamino)-4-methylpentanamideYield 25.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 2,3,4-trifluorobenzonitrile (265 mg, 1.68 mmol) in a flask, a solution of D-leucine amide hydrochloride (282 mg, 1.68 mmol) and DIEA (0.880 mL, 5.06 mmol) in DMSO (5 mL) was added. After being stirred at room temperature for 68 h, water and EtOAc were added. The organic phase was separated, washed with water, dried over Na2SO4, concentrated in vacuo. The residue was purified by a silica gel column, eluted with 0-70% EtOAc in hexane to give (R)-2-(4-cyano-2,3-difluorophenylamino)-4-methylpentanamide (113 mg).

Workup

  1. customThe organic phase was separated
  2. washwashed with water
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by a silica gel column
  6. washeluted with 0-70% EtOAc in hexane

Sources & evidence

ORD record
ord-f060f87e6e11480c8e47de3f50814b67
Source dataset
uspto-grants-2016_06
Patent number
US09359375B2

Reaction notes

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