Water → (R)-2-(4-cyano-3,5-difluorophenylamino)-4-methylpentanamide

HRID 2201061

Reaction equation

HRID 2201061 reaction equation
[F:1][C:2]1[CH:9]=[C:8](F)[CH:7]=[C:6]([F:11])[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[C:2]([F:1])=[CH:9][C:8]([NH:13][C@H:14]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:19]([NH2:21])=[O:20])=[CH:7][C:6]=1[F:11])#[N:5]

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 7371772,4,6-TrifluorobenzonitrileHCID 56776963(R)-2-Amino-4-methylpentanamide hydrochloride

Product 1

HCID 67509019(R)-2-(4-cyano-3,5-difluorophenylamino)-4-methylpentanamideYield 26.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2,4,6-trifluorobenzonitrile (208 mg, 1.32 mmol) in DMSO (2 mL), a solution of D-leucine amide hydrochloride (220 mg, 1.32 mmol) and DIEA (0.688 mL, 3.96 mmol) in DMSO (5 mL) was added. After being stirred at room temperature for 18 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 20-80% EtOAc in hexane to give (R)-2-(4-cyano-3,5-difluorophenylamino)-4-methylpentanamide (92 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 20-80% EtOAc in hexane

Sources & evidence

ORD record
ord-a5e14c12274847e1ab85fbded44b6354
Source dataset
uspto-grants-2016_06
Patent number
US09359375B2

Linked notes

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