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Potassium Carbonate → (R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-4-methylpentanamide

HRID 84834
Notes
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Reaction equation

HRID 84834 reaction equation
Br[C:2]1[C:3]([C:18]#[N:19])=[CH:4][C:5]([F:17])=[C:6]([NH:8][C@H:9]([CH2:13][CH:14]([CH3:16])[CH3:15])[C:10]([NH2:12])=[O:11])[CH:7]=1.Cl.[NH2:21][C:22]1[S:26][N:25]=[C:24]([CH3:27])[CH:23]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:18]([C:3]1[C:2]([NH:21][C:22]2[S:26][N:25]=[C:24]([CH3:27])[CH:23]=2)=[CH:7][C:6]([NH:8][C@H:9]([CH2:13][CH:14]([CH3:16])[CH3:15])[C:10]([NH2:12])=[O:11])=[C:5]([F:17])[CH:4]=1)#[N:19]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 67508329(R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-4-methylpentanamide

Product 1

HCID 67508594(R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-4-methylpentanamide

Reagents, catalysts & solvents

2
HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-4-methylpentanamide (175 mg, 0.533 mmol), 5-amino-3-methylisothiazole hydrochloride (97 mg, 0.644 mmol), BINAP (50 mg, 0.080 mmol), Pd(OAc)2 (35 mg, 0.156 mmol) and K2CO3 (250 mg, 1.81 mmol) in dioxane (4 mL) was degassed with Ar, then was stirred at 120 C for 18 h. Water and EtOAc were added. After being filtered, the filtrate was washed with water, dried over Na2SO4, concentrated in vacuo to give (R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-4-methylpentanamide as a crude residue.

Workup

  1. customwas degassed with Ar
  2. additionWater and EtOAc were added
  3. filtrationAfter being filtered
  4. washthe filtrate was washed with water
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4d2ee6170ca5471d8aab123fabda9431
Source dataset
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08846928B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes