Potassium Carbonate → (R)-3-(4-(1H-imidazol-1-yl)phenyl)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)propanamide

HRID 84903Notes

Reaction equation

HRID 84903 reaction equation
[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][C@@H:13]([NH:17][C:18]3[CH:23]=[C:22](Br)[C:21]([C:25]#[N:26])=[CH:20][C:19]=3[F:27])[C:14]([NH2:16])=[O:15])=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.Cl.[NH2:29][C:30]1[S:34][N:33]=[C:32]([CH3:35])[CH:31]=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.CS(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][C@@H:13]([NH:17][C:18]3[CH:23]=[C:22]([NH:29][C:30]4[S:34][N:33]=[C:32]([CH3:35])[CH:31]=4)[C:21]([C:25]#[N:26])=[CH:20][C:19]=3[F:27])[C:14]([NH2:16])=[O:15])=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 67514927HCID 67514927, compound

Product 1

HCID 67516101(R)-3-(4-(1H-imidazol-1-yl)phenyl)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)propanamideYield 14.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 679Dimethyl SulfoxideSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of (R)-3-(4-(1H-imidazol-1-yl)phenyl)-2-(5-bromo-4-cyano-2-fluorophenylamino)propanamide (59 mg, 0.137 mmol), 5-amino-3-methylisothiazole hydrochloride (35 mg, 0.232 mmol), K2CO3 (60 mg, 0.434 mmol), BINAP (25 mg, 0.040 mmol) and Pd(OAc)2 (15 mg, 0.066 mmol) in dioxane (2 mL) and DMSO (0.3 mL) was degassed with argon, then was stirred at 120 C for 18 h. The mixture was purified by HPLC to give (R)-3-(4-(1H-imidazol-1-yl)phenyl)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)propanamide (9 mg).

Workup

  1. customwas degassed with argon
  2. customThe mixture was purified by HPLC

Sources & evidence

ORD record
ord-476eed8009254ef9a20a9bec75b60563
Source dataset
uspto-grants-2014_09
Patent number
US08846928B2

Reaction notes

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