Tetrahydrofuran → 1-(3-Bromophenyl)-1-isopropyl-1H-isoindol-3-amine acetate

HRID 2264744Notes

Reaction equation

HRID 2264744 reaction equation
[CH:1]([Li])([CH3:3])[CH3:2].[Br:5][C:6]1[CH:7]=[C:8]([C:12]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[C:26]#[N:27])=[N:13]S(C(C)(C)C)=[O:15])[CH:9]=[CH:10][CH:11]=1.[O:28]1[CH2:32][CH2:31]CC1>CO>[NH3:13].[C:32]([OH:28])(=[O:15])[CH3:31].[Br:5][C:6]1[CH:7]=[C:8]([C:12]2([CH:1]([CH3:3])[CH3:2])[C:20]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:26]([NH2:27])=[N:13]2)[CH:9]=[CH:10][CH:11]=1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 72335434N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamideHCID 178506895HCID 178506895, compound

Product 2

HCID 222AmmoniaHCID 672723581-(3-Bromophenyl)-1-isopropyl-1H-isoindol-3-amine acetateYield 4.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Isopropyllithium (0.88 mL, 0.616 mmol, 0.7 M in pentane) was drop wise added to N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamide (Scheme #5, N) (0.200 g, 0.514 mmol) in tetrahydrofuran (5 mL) at −78° C. The temperature was allowed to rise to −25° C. after 2 h of stirring. The reaction was quenched with water (2 mL) and extracted with ethyl acetate. The organic phase was washed (water and brine), dried over magnesium sulfate and concentrated. The residue was dissolved in methanol (5 mL) and hydrochloric acid (1 mL, 1 M in diethyl ether) was added. The reaction mixture was stirred at room temperature for 18 h and was then concentrated. The residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic phase was washed (brine), dried over magnesium sulfate and concentrated. Purification by column chromatography using gradient eluation from dichloromethane to dichloromethane: 3.5 M ammonia in methanol 90:10 and preparative HPLC gave 9.0 mg (4.5% yield) of the title compound: 1H NMR (CDCl3) δ 7.97 (d, J=7.83 Hz, 1 H), 7.69 (t, J=1.89 Hz, 1 H), 7.67-7.63 (m, 1 H), 7.61-7.55 (m, 1 H), 7.55-7.45 (m, 2 H), 7.43-7.35 (m, 1 H), 7.22 (t, J=7.96 Hz, 1 H), 2.92-2.77 (m, 1 H), 2.11 (s, 3 H), 1.02 (d, J=6.82 Hz, 3 H), 0.63 (d, J=6.57 Hz, 3 H); MS (ES) m/z 329, 331 [M+1]+.

Workup

  1. customThe reaction was quenched with water (2 mL)
  2. extractionextracted with ethyl acetate
  3. washThe organic phase was washed (water and brine)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in methanol (5 mL)
  7. additionhydrochloric acid (1 mL, 1 M in diethyl ether) was added
  8. stirringThe reaction mixture was stirred at room temperature for 18 h
  9. concentrationwas then concentrated
  10. customThe residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate
  11. washThe organic phase was washed (brine)
  12. dry with materialdried over magnesium sulfate
  13. concentrationconcentrated
  14. customPurification by column chromatography

Sources & evidence

ORD record
ord-b6f5ae29286a43f0be3b70b4d13abda4
Source dataset
uspto-grants-2010_12
Patent number
US07855213B2

Reaction notes

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