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

HRID 2201115Notes

Reaction equation

HRID 2201115 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][N: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.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: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][N:15]=2)[C:10]([NH2:12])=[O:11])=[C:5]([F:20])[CH:4]=1)#[N:22]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 67509302(R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-(pyridin-2-yl)propanamide

Product 1

HCID 67508724(R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-3-(pyridin-2-yl)propanamideYield 38.9%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-(pyridin-2-yl)propanamide (125 mg, 0.344 mmol), 5-amino-3-methylisothiazole hydrochloride (80 mg, 0.531 mmol), K2CO3 (220 mg, 1.59 mmol), BINAP (40 mg, 0.064 mmol) and Pd(OAc)2 (30 mg, 0.133 mmol) in dioxane (3 mL) was degassed with argon, then was stirred at 120 C for 18 h. The mixture was concentrated in vacuo. The residue was purified by HPLC to give (R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-3-(pyridin-2-yl)propanamide (53 mg).

Workup

  1. customwas degassed with argon
  2. concentrationThe mixture was concentrated in vacuo
  3. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-e7ba7d83649941658b69b20984821615
Source dataset
uspto-grants-2016_06
Patent number
US09359375B2

Reaction notes

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