Trimethylsilyldiazomethane → 2-(4-Bromo-2-fluorophenylamino)-6-oxo-1,6-dihydropyridine-3-carboxylic acid

HRID 422795Notes

Reaction equation

HRID 422795 reaction equation
C[O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7](Cl)=[N:6][C:5]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([Br:18])=[CH:14][C:13]=1[F:19].BrC1C=CC(NC2N=C(Cl)C=CC=2C(O)=[O:32])=C(F)C=1.C[Si](C=[N+]=[N-])(C)C>CO.C1C=CC=CC=1>[Br:18][C:15]1[CH:16]=[CH:17][C:12]([NH:11][C:5]2[NH:6][C:7](=[O:32])[CH:8]=[CH:9][C:4]=2[C:3]([OH:2])=[O:20])=[C:13]([F:19])[CH:14]=1

Participants

5

Reactant 3

HCID 167693TrimethylsilyldiazomethaneHCID 635290422-(4-Bromo-2-fluorophenylamino)-6-chloro-nicotinic acidHCID 866723242-(4-Bromo-2-fluorophenylamino)-6-chloro-nicotinic acid methyl ester

Product 1

HCID 576368232-(4-Bromo-2-fluorophenylamino)-6-oxo-1,6-dihydropyridine-3-carboxylic acidYield 93%

Reagents, catalysts & solvents 1

HCID 21927730Benzene methanolSolvent

Procedure

Preparation of 2-(4-bromo-2-fluorophenylamino)-6-chloronicotinic acid methyl ester: To a suspension of 2-(4-bromo-2-fluorophenylamino)-6-chloronicotinic acid (5.00 g, 14.5 mmol) in methanol/benzene (1:1, 100 mL) under N2 was added (trimethylsilyl)diazomethane (2.0 M solution in hexanes) dropwise until the bubbling caused by gas evolution ceased. Solids precipitated out of solution. The reaction was allowed to stir for 1 hour. Excess (trimethylsilyl)diazomethane was quenched by the dropwise addition of glacial acetic acid. The precipitated solids were filtered and washed with methanol. The filtrate was concentrated to a smaller volume and additional solids precipitated out of solution that were filtered and washed with methanol. The solids were combined and dried under vacuum to yield 4.82 g (93%) of pure desired product as a dark pink solid.

Workup

  1. customSolids precipitated out of solution
  2. customExcess (trimethylsilyl)diazomethane was quenched by the dropwise addition of glacial acetic acid
  3. filtrationThe precipitated solids were filtered
  4. washwashed with methanol
  5. concentrationThe filtrate was concentrated to a smaller volume and additional solids
  6. customprecipitated out of solution that
  7. filtrationwere filtered
  8. washwashed with methanol
  9. customdried under vacuum

Sources & evidence

ORD record
ord-896a6aaa3e93430c986e1839f6705a7c
Source dataset
uspto-grants-2012_01
Patent number
US08101639B2

Reaction notes

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