3,3-Dimethylbutanoyl chloride → HCID 10076282, compound

HRID 1715379Notes

Reaction equation

HRID 1715379 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].[CH3:34][C:35]([CH3:41])([CH3:40])[CH2:36][C:37](Cl)=[O:38]>C(#N)C>[CH3:34][C:35]([CH3:41])([CH3:40])[CH2:36][C:37]([O:16][NH:15][C:14]([CH2:13][C@@H:12]([N:18]1[C:26](=[O:27])[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][C:24]=2[NH:28][C:29]([CH:31]2[CH2:33][CH2:32]2)=[O:30])[CH2:19]1)[C:6]1[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=1)=[O:17])=[O:38]

Participants

4

Reactant 2

HCID 815143,3-Dimethylbutanoyl chlorideHCID 10095424HCID 10095424, compound

Product 1

HCID 10076282HCID 10076282, compoundYield 59.3%

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 3,3-dimethyl-butyryl chloride (0.2 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-[2-(3,3-dimethyl-butyryloxycarbamoyl)-1-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide (360 mg, 59% yield): mp, 118-120° C.; 1H NMR (DMSO-d6) δ 0.87-0.89 (m, 4H, 2CH2), 0.98 (s, 9H, 3CH3), 1.31 (t, J=7 Hz, 3H, CH3), 1.73-1.80 (m, 1H, CH), 2.27 (s, 2H, CH2), 3.03-3.06 (m, 2H, CH2), 3.73 (s, 3H, CH3), 3.97-4.03 (m, 2H, CH2), 4.18 (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), 7.18 (d, J=8 Hz, 1H, Ar), 7.49 (d, J=8 Hz, 1H, Ar), 8.22 (d, J=8 Hz, 1H, Ar), 10.55 (s, 1H, NH), 11.82 (s, 1H, NH); 13C NMR (DMSO-d6) δ 7.75, 14.70, 15.46, 29.12, 30.53, 34.67, 44.24, 46.62, 51.11, 55.47, 63.80, 111.94, 112.09, 116.78, 117.33, 117.48, 119.25, 131.23, 132.73, 136.98, 142.26, 147.95, 148.56, 166.54, 168.06, 169.34, 171.70; Anal Calcd for C30H37N3O7+0.1H2O: C, 65.11; H, 6.78; N, 7.59. Found: C, 64.87; H, 6.87; N, 7.48.

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-3dc09c3f28b74376af52e783490a2eff
Source dataset
uspto-grants-2010_09
Patent number
US07799819B2

Reaction notes

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