Hydroxide → HCID 76119366, compound

HRID 880017Notes

Reaction equation

HRID 880017 reaction equation
N1CCCC(=O)[C:2]1=O.F[C:10]([C:13]1[C:14](=[O:20])[C:15](=[O:19])[N:16]=[CH:17][CH:18]=1)(F)F.FC(F)(S(F)(=O)=O)C(OC)=O.[OH-].[OH-].[Li+].[OH-].[Na+]>[Cu]I.CO.O1CCCC1.CN(C=O)C>[CH3:2][C:18]1[CH:17]=[N:16][C:15](=[O:19])[C:14](=[O:20])[C:13]=1[CH3:10]

Participants

11

Reactant 6

HCID 961HydroxideHCID 3939Lithium HydroxideHCID 14798Sodium HydroxideHCID 547667Methyl 2,2-difluoro-2-(fluorosulfonyl)acetateHCID 5163733Piperidine-2,3-dioneHCID 86730077HCID 86730077, compound2×

Product 1

HCID 76119366HCID 76119366, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

The ester (compound D, Scheme 1) can be treated with NIS in DMF to provide the C6 iodide (B). The resulting iodide (B) can be converted to trifluoromethylpyridinedione (C) by the treatment with methyl 2,2-difluoro-2-(fluorosulfonyl)acetate in the presence of copper (I) iodide in a solvent such as DMF. The ester (C) can be hydrolyzed using an aqueous hydroxide base such as lithium hydroxide or sodium hydroxide with a co-solvent such as tetrahydrofuran or methanol to provide the acid (D). The acid (D) can be coupled to an amine (RNH2) using standard peptide coupling conditions such as PyBOP/DIPEA or EDC/HOBT/DIPEA in a solvent such as dichloromethane or THF to produce the amide (E). The methoxy group on amide (E) could be cleaved using boron tribromide-methyl sulfide complex, boron tribromide solution in dichloromethane or boron trichloride to provide the pyridinedione (F).

Sources & evidence

ORD record
ord-cf8c53a7d6094b4d868a8d98eff59bcb
Source dataset
uspto-grants-2015_03
Patent number
US08993557B2

Reaction notes

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