Ethanol → HCID 131724265, compound

HRID 433300Notes

Reaction equation

HRID 433300 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]([N:17]2[C:25](=[O:26])[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][C:23]=3[NH2:27])[C:18]2=[O:28])[CH2:12][S:13]([CH3:16])(=[O:15])=[O:14])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[CH:29]1([C:32](Cl)=[O:33])[CH2:31][CH2:30]1.C(O)C>CCOCC>[CH:29]1([C:32]([NH:27][C:23]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:24]=2[C:25](=[O:26])[N:17]([CH:11]([C:5]2[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)[CH2:12][S:13]([CH3:16])(=[O:14])=[O:15])[C:18]3=[O:28])=[O:33])[CH2:31][CH2:30]1

Participants

5

Reactant 3

HCID 702EthanolHCID 77637Cyclopropanecarbonyl chlorideHCID 18758327HCID 18758327, compound

Product 1

HCID 131724265HCID 131724265, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A stirred mixture of 2-[1-(3,4-dimethoxyphenyl)-2-(methylsulfonyl)ethyl]-4-aminoisoindoline-1,3-dione (0.68 g, 1.7 mmol) and cyclopropane carbonyl chloride (1.3 mL) was heated to reflux for 25 min. To the mixture was added ethanol (10 mL) at 0° C. and kept for 30 min. The solvent was removed in vacuo to give a oil. The oil was stirred in ether (20 mL) for 30 min to give a suspension. The suspension was filtered and the solid washed with ether to give a white solid. The solid was purified by column chromatography (Silica Gel, 10% ethyl acetate in methylene chloride) to give cyclopropyl-N-{2-[1-(3,4-dimethoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}carboxamide as a white solid (330 mg, 42% yield); mp, 130-132° C.; 1H NMR (CDCl3) δ0.92-0.98 (m, 2H, 2CHH), 1.09-1.14 (m, 2H, 2CHH), 1.61-1.64 (m, 1H, CH), 2.88 (s, 3H, CH3), 3.73 (dd, J=4.4, 14.3 Hz, 1H, CHH), 3.86 (s, 3H, CH3), 3.90 (s, 3H, CH3), 4.58 (dd, J=10.4, 14.3 Hz, 1H, CHH), 5.90 (dd, J=4.4, 10.3 Hz, 1H, NCH), 6.84 (d, J=8 Hz, 1H, Ar), 7.09-7.14 (m, 2H, Ar), 7.47 (d, J=7.2 Hz, 1H, Ar), 7.65 (t, J=7.6 Hz, 1H, Ar), 8.75 (d, J=8.4 Hz, 1H, Ar), 9.68 (s, 1H, NH); 13C NMR (CDCl3) δ6.75, 16.13, 41.54, 48.43, 54.36, 55.81, 55.94, 110.98, 111.11, 114.78, 117.88, 120.27, 124.93, 129.30, 130.94, 136.00, 137.68, 149.19, 149.35, 167.45, 169.48, 172.79; Anal Calcd for C23H24N2O7S: C, 58.46; H, 5.12; N, 5.93. Found: C, 58.10; H, 5.16; N, 5.78.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 25 min
  3. customThe solvent was removed in vacuo
  4. customto give a oil
  5. customto give a suspension
  6. filtrationThe suspension was filtered
  7. washthe solid washed with ether
  8. customto give a white solid
  9. customThe solid was purified by column chromatography (Silica Gel, 10% ethyl acetate in methylene chloride)

Sources & evidence

ORD record
ord-7fb12dd60a6c47e1a8713bba856f8221
Source dataset
uspto-grants-2003_12
Patent number
US06667316B1

Reaction notes

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