Pivaloyl chloride → HCID 10369966, compound

HRID 1797253Notes

Reaction equation

HRID 1797253 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 (1 R)-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-0e7f07cd88364c57a95693cc32604df9
Source dataset
uspto-grants-2006_04
Patent number
US07034052B2

Reaction notes

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