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

HRID 2201084Notes

Reaction equation

HRID 2201084 reaction equation
Br[C:2]1[C:3]([C:17]#[N:18])=[CH:4][C:5]([F:16])=[C:6]([NH:8][C@H:9]([CH2:13][O:14][CH3:15])[C:10]([NH2:12])=[O:11])[CH:7]=1.Cl.[NH2:20][C:21]1[S:25][N:24]=[C:23]([CH3:26])[CH:22]=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:17]([C:3]1[C:2]([NH:20][C:21]2[S:25][N:24]=[C:23]([CH3:26])[CH:22]=2)=[CH:7][C:6]([NH:8][C@H:9]([CH2:13][O:14][CH3:15])[C:10]([NH2:12])=[O:11])=[C:5]([F:16])[CH:4]=1)#[N:18]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 67508869(R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-methoxypropanamide

Product 1

HCID 67508557(R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-3-methoxypropanamideYield 27.9%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-methoxypropanamide (52 mg, 0.164 mmol), 5-amino-3-methylisothiazole hydrochloride (40 mg, 0.265 mmol), K2CO3 (110 mg, 0.797 mmol), BINAP (30 mg, 0.048 mmol) and Pd(OAc)2 (25 mg, 0.111 mmol) in dioxane (2 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-methoxypropanamide (16 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-40101ed7fa8d4ec28e019578648da65a
Source dataset
uspto-grants-2016_06
Patent number
US09359375B2

Reaction notes

Loading…