Potassium Carbonate → 2-(4-Cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-4,4,4-trifluorobutanamide

HRID 2201121Notes

Reaction equation

HRID 2201121 reaction equation
Br[C:2]1[C:3]([C:19]#[N:20])=[CH:4][C:5]([F:18])=[C:6]([NH:8][CH:9]([CH2:13][C:14]([F:17])([F:16])[F:15])[C:10]([NH2:12])=[O:11])[CH:7]=1.Cl.[NH2:22][C:23]1[S:27][N:26]=[C:25]([CH3:28])[CH:24]=1.C([O-])([O-])=O.[K+].[K+].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>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:19]([C:3]1[C:2]([NH:22][C:23]2[S:27][N:26]=[C:25]([CH3:28])[CH:24]=2)=[CH:7][C:6]([NH:8][CH:9]([CH2:13][C:14]([F:17])([F:16])[F:15])[C:10]([NH2:12])=[O:11])=[C:5]([F:18])[CH:4]=1)#[N:20]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 675106812-(5-Bromo-4-cyano-2-fluorophenylamino)-4,4,4-trifluorobutanamide

Product 1

HCID 675082812-(4-Cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-4,4,4-trifluorobutanamideYield 99.6%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of 2-(5-bromo-4-cyano-2-fluorophenylamino)-4,4,4-trifluorobutanamide (90 mg, 0.254 mmol), 5-amino-3-methylisothiazole hydrochloride (58 mg, 0.385 mmol), K2CO3 (200 mg, 1.45 mmol), BINAP (35 mg, 0.056 mmol) and Pd(OAc)2 (23 mg, 0.100 mmol) in dioxane (3 mL) was degassed with argon, then was stirred at 120 C for 18 h. Water and EtOAc were added. The organic phase was separated, dried over Na2SO4, concentrated in vacuo to give 2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-4,4,4-trifluorobutanamide (98 mg).

Workup

  1. customwas degassed with argon
  2. additionWater and EtOAc were added
  3. customThe organic phase was separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a6ce2ac204d044048d8f19474642bbac
Source dataset
uspto-grants-2016_06
Patent number
US09359375B2

Reaction notes

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