Methanol → HCID 70936155, compound

HRID 2244529Notes

Reaction equation

HRID 2244529 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[NH2:28])[C:19]2=[O:29])[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].[CH:30]1([C:33](Cl)=[O:34])[CH2:32][CH2:31]1.CO>C(O)C>[CH:30]1([C:33]([NH:28][C:24]2[CH:23]=[CH:22][CH:21]=[C:20]3[C:25]=2[C:26](=[O:27])[N:18]([C@@H:12]([C:6]2[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=2)[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[C:19]3=[O:29])=[O:34])[CH2:32][CH2:31]1

Participants

5

Reactant 3

HCID 887MethanolHCID 77637Cyclopropanecarbonyl chlorideHCID 66718706APST-ZA

Product 1

HCID 70936155HCID 70936155, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A stirred mixture of 2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-4-aminoisoindoline-1,3-dione (1.3 g, 3.1 mmol) and cyclopropane carbonyl chloride (3 mL) was heated to reflux for 45 min. To the cooled mixture was added methanol (10 mL) at 0° C. and the mixture stirred for 30 min. The solvent was removed in vacuo to give an oil. The oil was stirred in ethanol (10 mL) for 2 h to give a suspension. The suspension was filtered and the solid washed with ethanol to give cyclopropyl-N-{2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}carboxamide as a white solid (1.3 g, 86% yield); mp, 140-141° C.; 1H NMR (CDCl3) δ 0.92-0.99 (m, 2H, 2CHH), 1.11-1.17 (m, 2H, 2CHH), 1.48 (t, J=6.9 Hz, 3H, CH3), 1.61-1.71 (m, 1H, CH), 2.88 (s, 3H, CH3), 3.75 (dd, J=4.4, 14.3 Hz, 1H, CHH), 3.86 (s, 3H, CH3), 4.12 (q, J=7.1 Hz, 2H, CH2), 4.57 (dd, J=10.4, 14.3 Hz, 1H, CHH), 5.89 (dd, J=4.4, 10.3 Hz, 1H, NCH), 6.84-6.88 (m, 1H, Ar), 7.11-7.15 (m, 2H, Ar), 7.48 (d, J=7.2 Hz, 1H, Ar), 7.65 (t, J=7.4 Hz, 1H, Ar), 8.76 (d, J=8.5 Hz, 1H, Ar), 9.69 (s, 1H, NH); 13C NMR (CDCl3) δ 8.71, 14.62, 16.16, 41.58, 48.59, 54.60, 55.89, 64.50, 111.49, 112.44, 114.83, 117.91, 120.26, 124.99, 129.27, 130.99, 136.02, 137.77, 148.63, 149.76, 167.49, 169.52, 172.79; Anal Calcd for C24H26N2O7S: C, 59.25; H, 5.39; N, 5.76. Found: C, 58.92; H, 5.21; N, 5.56.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 45 min
  3. customThe solvent was removed in vacuo
  4. customto give an oil
  5. customto give a suspension
  6. filtrationThe suspension was filtered
  7. washthe solid washed with ethanol

Sources & evidence

ORD record
ord-92c58d570e70440fa7e7f6e9a6fa0a85
Source dataset
uspto-grants-2010_03
Patent number
US07678825B2

Reaction notes

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