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

HRID 1661744Notes

Reaction equation

HRID 1661744 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-5e808bde661e44bc8363cd7a37d625e3
Source dataset
uspto-grants-2011_10
Patent number
US08030343B2

Reaction notes

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