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

HRID 84871Notes

Reaction equation

HRID 84871 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]([CH:13]2[CH2:15][CH2:14]2)[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]([CH:13]2[CH2:15][CH2:14]2)[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 67509451(R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-2-cyclopropylacetamide

Product 1

HCID 67508988(R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-2-cyclopropylacetamideYield 39.6%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-2-cyclopropylacetamide (87 mg, 0.278 mmol), 5-amino-3-methylisothiazole hydrochloride (63 mg, 0.418 mmol), K2CO3 (120 mg, 0.869 mmol), BINAP (40 mg, 0.064 mmol) and Pd(OAc)2 (20 mg, 0.089 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)-2-cyclopropylacetamide (38 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-52775199b05846bfa53cb005025bf996
Source dataset
uspto-grants-2014_09
Patent number
US08846928B2

Reaction notes

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