Cyclopropanecarbonyl chloride → HCID 10346622, compound

HRID 1715376Notes

Reaction equation

HRID 1715376 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].[CH:34]1([C:37](Cl)=[O:38])[CH2:36][CH2:35]1>C(#N)C>[CH:34]1([C:37]([O:16][NH:15][C:14]([CH2:13][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)[C:6]2[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=2)=[O:17])=[O:38])[CH2:36][CH2:35]1

Participants

4

Reactant 2

HCID 77637Cyclopropanecarbonyl chlorideHCID 10095424HCID 10095424, compound

Product 1

HCID 10346622HCID 10346622, compoundYield 66.2%

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 cyclopropanecarbonyl chloride (0.15 mL, 1.7 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-cyclopropanecarbonyloxycarbamoyl-1-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide (380 mg, 66% yield): mp, 130-132° C.; 1H NMR (DMSO-d6) δ 0.81-1.01 (2 ms, 8H, 4-CH2), 1.31 (t, J=7 Hz, 3H, CH3), 1.70-1.80 (m, 1H, CH), 2.97-3.05 (m, 2H, CH2), 3.73 (s, 3H, CH3), 3.97-4.04 (m, 2H, CH2), 4.17 (d, J=18 Hz, 1H, NCHH), 4.59 (d, J=18 Hz, 1H, NCHH), 5.66 (t, J=8 Hz, 1H, NCH), 6.87-6.94 (m, 3H, Ar), 7.18 (d, J=8 Hz, 1H, Ar), 7.49 (d, J=8 Hz, 1H, Ar), 8.23 (d, J=8 Hz, 1H, Ar), 10.54 (s, 1H, NH), 12.00 (s, 1H, NH); 13C NMR (DMSO-d6) δ 7.77, 8.92, 10.28, 14.69, 15.46, 34.61, 46.60, 51.11, 55.48, 63.80, 111.94, 112.11, 116.81, 117.31, 117.49, 119.27, 131.22, 132.77, 136.96, 142.25, 147.94, 148.57, 166.59, 168.85, 171.72, 172.41; Anal Calcd for C28H31N3O7+0.7H2O: C, 62.96; H, 6.11; N, 7.87. Found: C, 62.64; H, 5.89; N. 7.78.

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-ada0a95e37994ddd83af2c973797457b
Source dataset
uspto-grants-2010_09
Patent number
US07799819B2

Reaction notes

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