Chlorosuccinimide → Methyl 2-[(4-bromo-2-fluorophenyl)amino]-5-chloro-1,6-dihydro-1-methyl-6-oxo-3-pyridinecarboxylate

HRID 2068928Notes

Reaction equation

HRID 2068928 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:10]([CH3:20])[C:11](=[O:19])[CH:12]=[CH:13][C:14]=2[C:15]([O:17][CH3:18])=[O:16])=[C:4]([F:21])[CH:3]=1.[Cl:22]N1C(=O)CCC1=O>CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:10]([CH3:20])[C:11](=[O:19])[C:12]([Cl:22])=[CH:13][C:14]=2[C:15]([O:17][CH3:18])=[O:16])=[C:4]([F:21])[CH:3]=1

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 66673525Methyl 2-(4-bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate

Product 1

HCID 57636943Methyl 2-[(4-bromo-2-fluorophenyl)amino]-5-chloro-1,6-dihydro-1-methyl-6-oxo-3-pyridinecarboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 2-(4-bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate in DMF was added N-chlorosuccinimide. The reaction mixture was stirred at room temperature for 25 minutes and then quenched with saturated sodium bisulfite. The reaction mixture was diluted with H2O and partitioned between EtOAc/diethyl ether and saturated NaCl. The layers were separated and the aqueous layer was reextracted with EtOAc (1×). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. Purification by flash column chromatography (methylene chloride/EtOAc, 15:1) gave the desired product as a white solid. MS ESI (+) m/z 389, 391, 393 (M+, Cl, Br pattern) detected. 1H NMR (400 MHz, CDCl3) δ 9.88 (s, 1H), 8.13 (s, 1H), 7.34 (d, 1H), 7.24 (d, 1H), 6.69 (t, 1H), 3.87 (s, 3H), 3.29 (s, 3H).

Workup

  1. customquenched with saturated sodium bisulfite
  2. additionThe reaction mixture was diluted with H2O
  3. custompartitioned between EtOAc/diethyl ether and saturated NaCl
  4. customThe layers were separated
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customPurification by flash column chromatography (methylene chloride/EtOAc, 15:1)

Sources & evidence

ORD record
ord-127b56ba945f4c8eaea1841668457e8e
Source dataset
uspto-grants-2012_10
Patent number
US08299076B2

Reaction notes

Loading…