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

HRID 1662178Notes

Reaction equation

HRID 1662178 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([Mg]Br)=[CH:5][CH:4]=1.[Br:11][C:12]1[CH:13]=[C:14]([C:18]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:27]=2[C:33]#[N:34])=[N:19]S(C(C)(C)C)=O)[CH:15]=[CH:16][CH:17]=1.Cl>C1COCC1>[Br:11][C:12]1[CH:13]=[C:14]([C:18]2([C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[C:26]3[C:27](=[C:28]([F:32])[CH:29]=[CH:30][CH:31]=3)[C:33]([NH2:34])=[N:19]2)[CH:15]=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 76821598N-((3-bromophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamideHCID 178491912HCID 178491912, compound

Product 1

HCID 585795181-(3-Bromophenyl)-4-fluoro-1-(4-methoxyphenyl)-1H-isoindol-3-amineYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-Methoxyphenylmagnesium bromide (6.00 mL, 3.00 mmol) was added to a solution of N-((3-bromophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide (0.407 g, 1 mmol) in THF (10 mL) at 0° C. under an argon atmosphere. The resulting mixture was stirred and allowed to reach r.t. over night, then quenched with saturated aqueous NH4Cl, diluted with saturated aqueous NaHCO3 and extracted with DCM. The combined organics were passed through a phase separator (Sorbent) and concentrated. The residue was dissolved in MeOH (10 mL), and hydrogen chloride (2M in diethyl ether, 2 mL, 4 mmol) was added and the resulting mixture was stirred at r.t for 2.5 h. The mixture was concentrated in vacuo and purified on a silica gel column eluted with 0-5% 0.1M NH3 in MeOH in DCM to afford 0.39 g (95% yield) of the title compound: MS (ES+) m/z 411, 413 [M+1]+.

Workup

  1. waitto reach r.t. over night
  2. customquenched with saturated aqueous NH4Cl
  3. additiondiluted with saturated aqueous NaHCO3
  4. extractionextracted with DCM
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in MeOH (10 mL)
  7. stirringthe resulting mixture was stirred at r.t for 2.5 h
  8. concentrationThe mixture was concentrated in vacuo
  9. custompurified on a silica gel column
  10. washeluted with 0-5% 0.1M NH3 in MeOH in DCM

Sources & evidence

ORD record
ord-bff5000916b84ab7958787a670396b4a
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

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