1,8-Naphthyridine → 2,6-Dichloro-5-fluoro-4-methylpyridine-3-carboxylic acid

HRID 1081389Notes

Reaction equation

HRID 1081389 reaction equation
N1C2C(=CC=CN=2)C=C[CH:2]=1.[Cl:11][C:12]1[N:20]=[C:19]([Cl:21])[C:18]([F:22])=[CH:17][C:13]=1[C:14]([OH:16])=[O:15].C([N-]C(C)C)(C)C.[Li+]>C1COCC1>[Cl:11][C:12]1[N:20]=[C:19]([Cl:21])[C:18]([F:22])=[C:17]([CH3:2])[C:13]=1[C:14]([OH:16])=[O:15]

Participants

5

Reactant 3

HCID 1360691,8-NaphthyridineHCID 2724682Lithium diisopropylamideHCID 27336592,6-Dichloro-5-fluoronicotinic acid

Product 1

HCID 151303792,6-Dichloro-5-fluoro-4-methylpyridine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The introduction of the methyl group on the 1,8-naphthyridine substrate was accomplished by the formation of the di-anion of 2,6-dichloro-5-fluoronicotinic acid, preferably with lithium diisopropylamide in THF between -70° C. and -50° C. The di-anion was quenched with iodomethane and the target acid 2, 6-dichloro-5-fluoro-4-methylnicotinic acid is obtained after acidification. The remaining portion of the naphthyridine nucleus was elaborated using previously developed methodology.

Workup

  1. customThe di-anion was quenched with iodomethane

Sources & evidence

ORD record
ord-9fb0b60689164f3b9399f698b450abf1
Source dataset
uspto-grants-1996_12
Patent number
US05585491

Reaction notes

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