Isobutyryl chloride → HCID 10392039, compound

HRID 1797252Notes

Reaction equation

HRID 1797252 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C@H:12]([N:18]2[C:26](=[O:27])[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][C:24]=3[NH:28][C:29]([CH:31]3[CH2:33][CH2:32]3)=[O:30])[CH2:19]2)[CH2:13][C:14](=[O:17])[NH:15][OH:16])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].[C:34](Cl)(=[O:38])[CH:35]([CH3:37])[CH3:36]>C(#N)C>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C@H:12]([N:18]2[C:26](=[O:27])[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][C:24]=3[NH:28][C:29]([CH:31]3[CH2:33][CH2:32]3)=[O:30])[CH2:19]2)[CH2:13][C:14](=[O:17])[NH:15][O:16][C:34](=[O:38])[CH:35]([CH3:37])[CH3:36])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2]

Participants

4

Reactant 2

HCID 62325Isobutyryl chlorideHCID 10095424HCID 10095424, compound

Product 1

HCID 10392039HCID 10392039, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (1R)-cyclopropanecarboxylic acid {2-[1-(3-ethoxy-4-methoxy-phenyl)-2-hydroxycarbamoyl-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide (500 mg, 1.1 mmol) in acetonitrile (5 mL) was added isobutyryl chloride (0.15 mL, 1.4 mmol) at room temperature and kept for 24 hrs. The solution was extracted with ethyl acetate (50 mL) and sodium hydrogen carbonate (50 mL, sat). The organic layer was dried over MgSO4. Filtration and removal of solvent gave (1R)-cyclopropanecarboxylic acid {2-[1-(3-ethoxy-4-methoxy-phenyl)-2-isobutyryloxycarbamoyl-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide (380 mg, 66% yield): mp, 107–109° C.; 1H NMR (DMSO-d6) δ 0.86–0.89 (m, 4H, 2CH2), 1.10 (d, J=7 Hz, 6H, 2CH3), 1.31 (t, J=7 Hz, 3H, CH3), 1.73–1.81 (m, 1H, CH), 2.62–2.73 (m, 1H, CH), 3.02–3.05 (m, 2H, CH2), 3.73 (s, 3H, CH3), 3.96–4.05 (m, 2H, CH2), 4.19 (d, J=18 Hz, 1H, NCHH), 4.59 (d, J=18 Hz, 1H, NCHH), 5.67 (t, J=8 Hz, 1H, NCH), 6.86–6.94 (m, 3H, Ar), 7.19 (d, J=8 Hz, 1H, Ar), 7.50 (d, J=8 Hz, 1H, Ar), 8.23 (d, J=8 Hz, 1H, Ar), 10.54 (s, 1H, NH), 11.86 (s, 1H, NH); 13C NMR (DMSO-d6) δ 7.76, 14.69, 15.46, 18.65, 31.27, 34.64, 46.59, 51.07, 55.47, 63.80, 111.93, 112.09, 116.82, 117.32, 117.50, 119.27, 131.23, 132.77, 136.98, 142.25, 147.95, 148.58, 166.61, 168.04, 171.72, 174.29; Anal Calcd for C28H33N3O7+0.11 H2O: C, 63.99; H, 6.37; N, 8.00; H2O, 0.38. Found: C, 63.64; H, 6.37; N, 7.70; H2O, 0.39.

Workup

  1. extractionThe solution was extracted with ethyl acetate (50 mL) and sodium hydrogen carbonate (50 mL, sat)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationFiltration and removal of solvent

Sources & evidence

ORD record
ord-a6a934e7d9e7446ba0ac9ab4b432c7a4
Source dataset
uspto-grants-2006_04
Patent number
US07034052B2

Reaction notes

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