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

HRID 2264742Notes

Reaction equation

HRID 2264742 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[Br:6][C:7]1[CH:8]=[C:9]([C:13]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[C:27]#[N:28])=[N:14]S(C(C)(C)C)=[O:16])[CH:10]=[CH:11][CH:12]=1.[O:29]1[CH2:33][CH2:32]CC1>>[C:33]([OH:29])(=[O:16])[CH3:32].[Br:6][C:7]1[CH:8]=[C:9]([C:13]2([CH:1]3[CH2:3][CH2:2]3)[C:21]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:27]([NH2:28])=[N:14]2)[CH:10]=[CH:11][CH:12]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 72335434N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamideHCID 178418630HCID 178418630, compound

Product 1

HCID 672723191-(3-Bromophenyl)-1-cyclopropyl-1H-isoindol-3-amine acetateYield 11%

Conditions

Temperature
30 °C

Procedure

Cyclopropylmagnesium bromide (7.20 mL, 3.60 mmol, 0.5 M in tetrahydrofuran) was added drop wise to N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamide (Scheme #5, N) (1.00 g, 2.57 mmol) in dry tetrahydrofuran (10 mL) at room temperature under argon atmosphere. The reaction was heated to 30° C. and stirred for 2.5 h, then cooled to 0° C. The reaction was quenched with methanol (5 mL) and extracted twice with ethyl acetate. The organic phases were pooled, washed (saturated aqueous ammonium chloride and water), dried over magnesium sulfate and concentrated. Column chromatography using gradient solution from dichloromethane to dichloromethane:3.5 M ammonia in methanol 97:3 followed by preparative HPLC (Column: Gemini C8; Mobile phase: 35% acetonitrile in 0.1 M ammonium acetate/water; Flow: 1 mL/min) afforded 0.108 g (11% yield) of the title compound: 1H NMR (DMSO-d6) δ 7.72-7.69 (m, 1 H), 7.62-7.57 (m, 3 H), 7.40-7.35 (m, 3 H), 7.25 (t, J=7.78 Hz, 1 H), 1.89 (s, 3 H), 1.86-1.81 (m, 1 H), 0.46-0.35 (m, 2 H), 0.21-0.13 (m, 1 H), −0.09-−0.02 (m, 1 H); MS (ES) m/z 327, 329 [M+1]+.

Workup

  1. temperaturecooled to 0° C
  2. customThe reaction was quenched with methanol (5 mL)
  3. extractionextracted twice with ethyl acetate
  4. washwashed (saturated aqueous ammonium chloride and water)
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-4411e1687218416299d48e00728bfb91
Source dataset
uspto-grants-2010_12
Patent number
US07855213B2

Reaction notes

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