Acetic Acid → (R)-2-(4-cyano-3-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-4-methylpentanamide

HRID 2201062

Reaction equation

HRID 2201062 reaction equation
[C:1]([C:3]1[C:8]([F:9])=[CH:7][C:6]([NH:10][C@H:11]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:12]([NH2:14])=[O:13])=[CH:5][C:4]=1F)#[N:2].Cl.[NH2:21][C:22]1[S:26][N:25]=[C:24]([CH3:27])[CH:23]=1.[H-].[Na+].CC(O)=O>CS(C)=O>[C:1]([C:3]1[C:4]([NH:21][C:22]2[S:26][N:25]=[C:24]([CH3:27])[CH:23]=2)=[CH:5][C:6]([NH:10][C@H:11]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:12]([NH2:14])=[O:13])=[CH:7][C:8]=1[F:9])#[N:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 67509019(R)-2-(4-cyano-3,5-difluorophenylamino)-4-methylpentanamide

Product 1

HCID 67510110(R)-2-(4-cyano-3-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-4-methylpentanamideYield 30.9%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of (R)-2-(4-cyano-3,5-difluorophenylamino)-4-methylpentanamide (92 mg, 0.34 mmol) and 5-amino-3-methylisothiazole hydrochloride (70 mg, 0.46 mmol) in DMSO (2 mL), NaH (60% in mineral oil, 80 mg, 2.00 mmol) was added. H2 gas evolved. The mixture was stirred at 130 C for 1 h. After being acidified with HOAc (1.0 mL), the mixture was purified by HPLC to give (R)-2-(4-cyano-3-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-4-methylpentanamide (38 mg).

Workup

  1. customthe mixture was purified by HPLC

Sources & evidence

ORD record
ord-a3c2c777863647fa84351519fb308c3b
Source dataset
uspto-grants-2016_06
Patent number
US09359375B2

Linked notes

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