Pivaloyl chloride → HCID 10369966, compound

HRID 1715378Notes

Reaction equation

HRID 1715378 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]([CH3:40])([CH3:39])[C:36](Cl)=[O:37]>C(#N)C>[CH3:34][C:35]([CH3:40])([CH3:39])[C:36]([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:37]

Participants

4

Reactant 2

HCID 62493Pivaloyl chlorideHCID 10095424HCID 10095424, compound

Product 1

HCID 10369966HCID 10369966, compoundYield 42%

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 (180 mg, 0.4 mmol) in acetonitrile (2 mL) was added 2,2-dimethyl-propionyl chloride (0.064 mL, 0.5 mmol) at room temperature and kept for 24 hrs. The solution was extracted with ethyl acetate (15 mL) and sodium hydrogen carbonate (15 mL, sat). The organic layer was dried over MgSO4. Filtration and removal of solvent gave (1R)-cyclopropanecarboxylic acid {2-[2-(2,2-dimethyl-propionyloxycarbamoyl)-1-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide (90 mg, 42% yield): mp, 146-148° C.; 1H NMR (DMSO-d6) δ 0.87-0.89 (m, 4H, 2CH2), 1.19 (s, 9H, 3CH3), 1.30 (t, J=7 Hz, 3H, CH3), 1.76-1.82 (m, 1H, CH), 3.04 (d, J=8 Hz, 2H, CH2), 3.73 (s, 3H, CH3), 3.97-4.05 (m, 2H, CH2), 4.19 (d, J=18 Hz, 1H, NCHH), 4.58 (d, J=18 Hz, 1H, NCHH), 5.66 (t, J=8 Hz, 1H, NCH), 6.87-6.94 (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), 10.55 (s, 1H, NH), 11.82 (s, 1H, NH); 13C NMR (DMSO-d6) δ 7.77, 14.69, 15.46, 26.71, 34.63, 37.63, 46.61, 51.03, 55.46, 63.78, 111.91, 112.07, 116.82, 117.32, 117.51, 119.24, 131.24, 132.76, 136.96, 142.24, 147.92, 148.55, 166.66, 168.00, 171.71, 175.41; Anal Calcd for C29H35N3O7: C, 64.79; H, 6.56; N, 7.82. Found: C, 64.91; H, 6.50; N, 7.84.

Workup

  1. extractionThe solution was extracted with ethyl acetate (15 mL) and sodium hydrogen carbonate (15 mL, sat)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationFiltration and removal of solvent

Sources & evidence

ORD record
ord-73242d53ab324c529aa3da2bb33555ec
Source dataset
uspto-grants-2010_09
Patent number
US07799819B2

Reaction notes

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