Acetic Acid → 2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-(pyrrolylmethyl)isoindoline-1,3-dione

HRID 2244517Notes

Reaction equation

HRID 2244517 reaction equation
[NH2:1][CH2:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[C:5](=[O:30])[N:6]([CH:13]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH2:28][CH3:29])[CH:20]=1)[CH2:14][S:15]([CH3:18])(=[O:17])=[O:16])C2=O.COC1[CH2:37][CH2:36][CH:35](OC)O1.[C:40]([OH:43])(=O)[CH3:41]>>[CH2:28]([O:27][C:21]1[CH:20]=[C:19]([CH:13]([N:6]2[C:40](=[O:43])[C:41]3[C:4](=[CH:8][CH:9]=[CH:10][C:11]=3[CH2:3][C:2]3[NH:1][CH:35]=[CH:36][CH:37]=3)[C:5]2=[O:30])[CH2:14][S:15]([CH3:18])(=[O:16])=[O:17])[CH:24]=[CH:23][C:22]=1[O:25][CH3:26])[CH3:29]

Participants

4

Reactant 3

HCID 176Acetic AcidHCID 790982,5-DimethoxytetrahydrofuranHCID 116699704-(Aminomethyl)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]isoindoline-1,3-dione

Product 1

HCID 667184982-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-(pyrrolylmethyl)isoindoline-1,3-dioneYield 60%

Procedure

A mixture of 4-(aminomethyl)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]isoindoline-1,3-dione (0.34 g, 0.79 mmol) and 2,5-dimethoxytetrahydrofuran (0.10 g, 0.79 mmol) in acetic acid (5 mL) was heated to reflux for 1 hour. The reaction mixture was then concentrated in vacuo and the residue was stirred with ethyl acetate (50 mL) and saturated sodium bicarbonate (25 mL). The organic layer was washed with water (25 mL), brine (25 mL), dried and concentrated. The residue was purified by flash chromatography (methylene chloride:ethyl acetate, 95:5) to afford 2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-(pyrrolylmethyl)isoindoline-1,3-dione (0.23 g, 60% yield): mp 80-82° C.; 1H NMR (CDCl3) δ 7.71 (d, J=7.3 Hz, 1H, Ar), 7.57 (t, J=7.7 Hz, 1H, Ar), 7.26 (m, 2H, Ar), 7.15 (d, J=7.0 Hz, 2H, Ar), 6.96 (d, J=7.8 Hz, 1H, Ar), 6.71 (d, J=1.7 Hz, 1H, Ar), 6.22 (d, J=1.8 Hz, 1H, Ar) 5.94-5.88 (dd, J=4.4 and 10.3 Hz, 1H, NCH), 5.57 (s, 2H, CH2), 4.63-4.53 (dd, J=10.7, 14.4 Hz, 1H, CHH), 4.13 (q, J=7.0 Hz, 2H, CH2), 3.85 (s, 3H, CH3), 3.80-3.72 (dd, J=4.4,14.4 Hz, 1H, CHH), 2.86 (s, 3H, CH3), 1.47 (t, J=6.9 Hz, 3H, CH3); 13C NMR (CDCl3) δ 168.08, 167.69, 149.72, 148.63, 138.71, 134.74, 132.65, 131.86, 129.44, 126.92, 122.69, 121.46, 120.47, 112.49, 111.44, 109.15, 64.51, 55.95, 54.65, 48.73, 48.57, 41.58, 14.69; Anal. Calcd for C25H26N2O6S: C, 62.23; H, 5.43; N, 5.81; S. 6.64. Found: C, 62.25; H, 5.56; N, 5.63; S, 6.83.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 1 hour
  3. concentrationThe reaction mixture was then concentrated in vacuo
  4. washThe organic layer was washed with water (25 mL), brine (25 mL)
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (methylene chloride:ethyl acetate, 95:5)

Sources & evidence

ORD record
ord-c481bbb16e8143aa9772af58a67ccd7e
Source dataset
uspto-grants-2010_03
Patent number
US07678825B2

Reaction notes

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