Hydrochloric Acid → 1-(3-Bromophenyl)-1-(3,4-difluoro-5-methoxyphenyl)-4-fluoro-1H-isoindol-3-amine

HRID 1662199Notes

Reaction equation

HRID 1662199 reaction equation
[Mg].[Li+].[Cl-].CC(C[AlH]CC(C)C)C.Br[C:14]1[CH:15]=[C:16]([O:22][CH3:23])[C:17]([F:21])=[C:18]([F:20])[CH:19]=1.[Br:24][C:25]1[CH:26]=[C:27]([C:31]([C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[C:40]=2[C:46]#[N:47])=[N:32]S(C(C)(C)C)=O)[CH:28]=[CH:29][CH:30]=1.Cl>C1COCC1.CO>[Br:24][C:25]1[CH:26]=[C:27]([C:31]2([C:14]3[CH:15]=[C:16]([O:22][CH3:23])[C:17]([F:21])=[C:18]([F:20])[CH:19]=3)[C:39]3[C:40](=[C:41]([F:45])[CH:42]=[CH:43][CH:44]=3)[C:46]([NH2:47])=[N:32]2)[CH:28]=[CH:29][CH:30]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 14487Diisobutylaluminum hydrideHCID 433294Lithium ChlorideHCID 27732885-Bromo-1,2-difluoro-3-methoxybenzeneHCID 5462224MagnesiumHCID 76821598N-((3-bromophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide

Product 1

HCID 585795071-(3-Bromophenyl)-1-(3,4-difluoro-5-methoxyphenyl)-4-fluoro-1H-isoindol-3-amineYield 14%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent4×

Procedure

Magnesium turnings (0.692 g, 28.47 mmol) were stirred under Ar(g) for 10 min and LiCl 0.5M in THF (28.5 mL, 14.24 mmol) was added followed by DIBAL-H 1M in THF (0.228 mL, 0.23 mmol). The mixture was stirred for 5 min and then 5-bromo-1,2-difluoro-3-methoxybenzene (2.54 g, 11.39 mmol) in 5 mL THF was added in one portion and stirred for 1 h. The mixture was added to N-((3-bromophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide (4.64 g, 11.39 mmol) in THF (20 mL) and stirred 1 h. MeOH (3 mL) was added and the mixture was treated with HCl in 2.0 MeOH (22.78 mL, 22.78 mmol) for 1 h. NaHCO3(sat) was added and the mixture was extracted with EtOAc. The organic phase was washed with brine, dried over MgSO4 and concentrated. The residue was purified by preparative HPLC to give 714 mg (14%) of the title product as a solid. MS (ES+) m/z 447, 449 [M+H]+.

Workup

  1. stirringstirred for 1 h
  2. stirringstirred 1 h
  3. extractionthe mixture was extracted with EtOAc
  4. washThe organic phase was washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-803baa96284448e9ad392a5f92265029
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

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