Sodium Sulfite → 2-Bromo-5-(5-chloro-2-fluoro-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one

HRID 2204342Notes

Reaction equation

HRID 2204342 reaction equation
[O-]S([C:5]([F:8])(F)F)(=O)=O.F[N+]1C(C)=CC(C)=CC=1C.[Br:19][C:20]1[N:24]([CH:25]([CH3:27])[CH3:26])[C:23]2[CH:28]([C:41]3[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][CH:42]=3)[N:29]([C:32]3[CH:37]=[C:36]([Cl:38])[C:35](=[O:39])[N:34](C)[CH:33]=3)[C:30](=[O:31])[C:22]=2[CH:21]=1.S([O-])([O-])=O.[Na+].[Na+]>ClCCCl>[Br:19][C:20]1[N:24]([CH:25]([CH3:27])[CH3:26])[C:23]2[CH:28]([C:41]3[CH:42]=[CH:43][C:44]([Cl:47])=[CH:45][CH:46]=3)[N:29]([C:32]3[CH:37]=[C:36]([Cl:38])[C:35](=[O:39])[N:34]([CH3:33])[C:5]=3[F:8])[C:30](=[O:31])[C:22]=2[CH:21]=1

Participants

5

Reactant 3

HCID 24437Sodium SulfiteHCID 27245751-Fluoro-2,4,6-trimethylpyridinium Trifluoromethanesulfonate [Fluorinating Reagent]HCID 867031442-bromo-5-(5-chloro-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one2×

Product 1

HCID 867031432-Bromo-5-(5-chloro-2-fluoro-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
80 °C

Procedure

1-Fluoro-2,4,6-trimethyl-pyridinium triflate [107264-00-6] (1.476 mmol) was added to a solution of 2-bromo-5-(5-chloro-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one (Intermediate E) (0.738 mmol) in 1,2-dichloroethane (12 mL) and then the mixture was heated to 80° C. in the dark. After 12 h, the reaction mixture was cooled to rt, poured into a 2% aqueous solution of sodium sulfite and extracted with EtOAc (2×). The combined organic layers were successively washed with 1M aqueous citric acid, 1M aqueous NaHCO3 and brine, dried (Na2SO4), filtered and concentrated. The residue was purified using a RediSep® silica gel column to afford the title compound as a pink foam. ESI-MS: tR=1.16 min, [M]+ 512/514/516 (LC-MS 1); TLC: Rf=0.10 (1.1 EtOAc/heptanes).

Workup

  1. temperaturethe reaction mixture was cooled to rt
  2. extractionextracted with EtOAc (2×)
  3. washThe combined organic layers were successively washed with 1M aqueous citric acid, 1M aqueous NaHCO3 and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified

Sources & evidence

ORD record
ord-d7d9ac53f51748369a5f16555c475a0d
Source dataset
uspto-grants-2016_06
Patent number
US09365576B2

Reaction notes

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