2-chloro-N-({2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}methyl)acetamide → HCID 18758314, compound

HRID 1661774Notes

Reaction equation

HRID 1661774 reaction equation
[CH3:1][NH:2][CH3:3].CO.Cl[CH2:7][C:8]([NH:10][CH2:11][C:12]1[CH:20]=[CH:19][CH:18]=[C:17]2[C:13]=1[C:14](=[O:39])[N:15]([CH:22]([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[C:30]([O:36][CH2:37][CH3:38])[CH:29]=1)[CH2:23][S:24]([CH3:27])(=[O:26])=[O:25])[C:16]2=[O:21])=[O:9]>O1CCCC1>[CH3:1][N:2]([CH3:3])[CH2:7][C:8]([NH:10][CH2:11][C:12]1[CH:20]=[CH:19][CH:18]=[C:17]2[C:13]=1[C:14](=[O:39])[N:15]([CH:22]([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[C:30]([O:36][CH2:37][CH3:38])[CH:29]=1)[CH2:23][S:24]([CH3:27])(=[O:26])=[O:25])[C:16]2=[O:21])=[O:9]

Participants

4

Reactant 2

HCID 187583802-chloro-N-({2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}methyl)acetamideHCID 22497844Dimethylamine methanol

Product 1

HCID 18758314HCID 18758314, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Dimethylamine/methanol (2.0 M, 2.95 mL) was added to a stirred solution of 2-chloro-N-({2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}methyl)acetamide (1.0 g, 1.96 mmol) in tetrahydrofuran and the mixture was stirred at room temperature for 24 hours. The tetrahydrofuran was removed in vacuo and the residue was dissolved in methylene chloride (60 mL). The methylene chloride solution was washed with water (30 mL), brine (30 mL) and dried over magnesium sulfate. The solvent was removed in vacuo and the residue was purified by chromatography (silica gel, methylene chloride:methanol 97.5:2.5) to give 2-(dimethylamino)-N-({2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}methyl)acetamide (0.6 g, 59%). To as stirred solution of the amine in ethyl acetate (10 mL) was added 1N hydrogen chloride in ether (4 mL). The resulting suspension was filtered and washed with ether to give 2-(dimethylamino)-N-({2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]1,3-dioxoisoindolin-4-yl}methyl)acetamide hydrochloride (0.55 g) as a white solid: mp 103-105° C.; 1H NMR (DMSO-d6) δ 10.06 (s, 1H), 9.37 (m, 1H), 7.83-7.73 (m, 3H), 7.10 (s, 1H), 6.97-6.92 (m, 2H), 5.82-5.76 (dd, J=4.1, 10.2 Hz, 1H), 4.81 (d, J=5.6 Hz, 2H), 4.38-4.32 (dd, J=10.3, 14.1 Hz, 1H), 4.19-4.12 (dd, J=4.4, 14.4 Hz, 1H), 4.05-3.08 (m, 4H), 3.73 (s, 3H0, 3.02 (s, 3H), 2.82 (s, 6H0, 1.32 (t, J=6.9 Hz, 3H); 13C NMR (DMSO-d6) δ 167.60, 167.20, 164.79, 148.88, 147.85, 137.84, 134.69, 133.36, 131.51, 129.59, 127.09, 122.14, 119.79, 112.41, 111.76, 63.84, 57.17, 55.49, 52.98, 47.29, 43.13, 41.09, 37.82, 14.67; Anal. Calcd. for C26H32N3O7SCl+0.56H2O: C, 53.23; H, 5.92; N, 7.45, S, 5.68; Cl, 6.28. Found: C, 53.22; H, 5.87; N, 7.37; S, 5.64; Cl, 6.52.

Workup

  1. customThe tetrahydrofuran was removed in vacuo
  2. dissolutionthe residue was dissolved in methylene chloride (60 mL)
  3. washThe methylene chloride solution was washed with water (30 mL), brine (30 mL)
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was removed in vacuo
  6. customthe residue was purified by chromatography (silica gel, methylene chloride:methanol 97.5:2.5)

Sources & evidence

ORD record
ord-438cb1df0d1945649868953b2fd7669a
Source dataset
uspto-grants-2011_10
Patent number
US08030343B2

Reaction notes

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