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

HRID 84840Notes

Reaction equation

HRID 84840 reaction equation
Br[C:2]1[C:3]([C:21]#[N:22])=[CH:4][C:5]([F:20])=[C:6]([NH:8][C@H:9]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:10]([NH2:12])=[O:11])[CH:7]=1.Cl.[NH2:24][C:25]1[S:29][N:28]=[C:27]([CH3:30])[CH:26]=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].CCOC(C)=O.O>[C:21]([C:3]1[C:2]([NH:24][C:25]2[S:29][N:28]=[C:27]([CH3:30])[CH:26]=2)=[CH:7][C:6]([NH:8][C@H:9]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:10]([NH2:12])=[O:11])=[C:5]([F:20])[CH:4]=1)#[N:22]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 67508222(R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-phenylpropanamide

Product 1

HCID 67508807(R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-3-phenylpropanamide

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalyst2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-phenylpropanamide (362 mg, 1.00 mmol), 5-amino-3-methylisothiazole hydrochloride (166 mg, 1.10 mmol), BINAP (70 mg, 0.112 mmol), Pd(OAc)2 (35 mg, 0.156 mmol) and K2CO3 (430 mg, 3.11 mmol) in dioxane (5 mL) was degassed with Ar, then was stirred at 120 C for 18 h. More Pd(OAc)2 (35 mg, 0.156 mmol) was added. The mixture was stirred at 120 C for another 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)-3-phenylpropanamide as a crude residue.

Workup

  1. customwas degassed with Ar
  2. stirringThe mixture was stirred at 120 C for another 18 h
  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-8864d7801c66454185a1b0b630c6c300
Source dataset
uspto-grants-2014_09
Patent number
US08846928B2

Reaction notes

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