Hydrochloric Acid → 6-chloro-4-fluoro-1-(3-methoxyphenyl)-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-isoindol-3-amine

HRID 1662221Notes

Reaction equation

HRID 1662221 reaction equation
C([Li])(C)(C)C.Br[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:8]=1.[Cl:17][C:18]1[CH:19]=[C:20]([F:42])[C:21]([C:40]#[N:41])=[C:22]([C:24]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH3:39])[CH:33]=2)=[N:25]S(C(C)(C)C)=O)[CH:23]=1.Cl.CO>C1COCC1>[Cl:17][C:18]1[CH:23]=[C:22]2[C:21]([C:40]([NH2:41])=[N:25][C:24]2([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH3:39])[CH:33]=2)[C:7]2[CH:12]=[CH:11][N:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:8]=2)=[C:20]([F:42])[CH:19]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 234369504-Bromo-2-(trifluoromethyl)pyridineHCID 76821604N-((5-chloro-2-cyano-3-fluorophenyl)(3-methoxyphenyl)methylene)-2-methylpropane-2-sulfinamideHCID 178418306HCID 178418306, compound

Product 1

HCID 585795226-chloro-4-fluoro-1-(3-methoxyphenyl)-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-isoindol-3-amineYield 39.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

tert-Butyllithium (1.7 M in pentane, 6.59 mL, 11.20 mmol) was added dropwise to THF (10 mL) at −100° C. under an argon atmosphere. A solution of 4-bromo-2-trifluoromethylpyridine (1.266 g, 5.60 mmol) in THF (1 mL) was added dropwise followed by the addition of N-((5-chloro-2-cyano-3-fluorophenyl)(3-methoxyphenyl)methylene)-2-methylpropane-2-sulfinamide (2 g, 5.09 mmol) in THF (6 mL). The resulting reaction mixture was left on the thawing cooling bath for 30 min then the cooling bath was removed and the mixture was stirred at rt for 1.5 h. Hydrogen chloride in methanol solution (20.36 mL, 25.45 mmol) was added and the mixture was stirred at rt for 1 h. The mixture was concentrated and purified on a silica gel column eluted with 0-10% 0.1M NH3 in MeOH in DCM to afford 870 mg (39%) of the title compound.

Workup

  1. customThe resulting reaction mixture
  2. waitwas left on the thawing
  3. temperaturecooling bath for 30 min
  4. customthe cooling bath was removed
  5. stirringthe mixture was stirred at rt for 1 h
  6. concentrationThe mixture was concentrated
  7. custompurified on a silica gel column
  8. washeluted with 0-10% 0.1M NH3 in MeOH in DCM

Sources & evidence

ORD record
ord-08130cc2435e4e49a6bf70b955b1c3b6
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

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