Hydrochloric Acid → 5-(3-Amino-1-(3-bromophenyl)-4-fluoro-1H-isoindol-1-yl)-2-methoxy-3-methylbenzonitrile

HRID 1662218Notes

Reaction equation

HRID 1662218 reaction equation
[Mg].[Li+].[Cl-].CC(C[AlH]CC(C)C)C.Br[C:14]1[CH:15]=[C:16]([CH3:24])[C:17]([O:22][CH3:23])=[C:18]([CH:21]=1)[C:19]#[N:20].[Br:25][C:26]1[CH:27]=[C:28]([C:32]([C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[C:41]=2[C:47]#[N:48])=[N:33]S(C(C)(C)C)=O)[CH:29]=[CH:30][CH:31]=1.Cl>C1COCC1.CO>[NH2:48][C:47]1[C:41]2[C:40](=[CH:45][CH:44]=[CH:43][C:42]=2[F:46])[C:32]([C:14]2[CH:15]=[C:16]([CH3:24])[C:17]([O:22][CH3:23])=[C:18]([CH:21]=2)[C:19]#[N:20])([C:28]2[CH:29]=[CH:30][CH:31]=[C:26]([Br:25])[CH:27]=2)[N:33]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 14487Diisobutylaluminum hydrideHCID 433294Lithium ChlorideHCID 5462224MagnesiumHCID 459232975-Bromo-2-methoxy-3-methylbenzonitrileHCID 76821598N-((3-bromophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide

Product 1

HCID 585794945-(3-Amino-1-(3-bromophenyl)-4-fluoro-1H-isoindol-1-yl)-2-methoxy-3-methylbenzonitrileYield 32%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranCatalystHCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent3×

Procedure

Magnesium turnings (37.3 mg, 1.53 mmol) were stirred under Ar(g) for 10 min and LiCl 0.5M in THF (1.841 mL, 0.92 mmol) was added followed by DIBAL-H 1M in THF (6.14 μL, 6.14 μmol). The mixture was stirred for 5 min and 5-bromo-2-methoxy-3-methylbenzonitrile (194 mg, 0.86 mmol) in THF (1 mL) was added in one portion and stirring was continued for 2 h. The solution was transferred via canula to N-((3-bromophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide (250 mg, 0.61 mmol) in THF (3 mL) at rt and stirred o.n. MeOH (4 mL) was added and the mixture was treated with HCl in MeOH (1.473 mL, 1.84 mmol) o.n. The solvents were removed in vacuo, and the residue was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate. The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. Purification by silica gel chromatography using a gradient of 0 to 2.5% (3.5 M ammonia in methanol) in dichloromethane afforded 0.088 g (32% yield) of the title compound.

Workup

  1. stirringstirring
  2. waitwas continued for 2 h
  3. stirringstirred o.n
  4. customThe solvents were removed in vacuo
  5. customthe residue was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-b5b7e626cdd94c479392660a9367ecc3
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

Loading…