Dimethylamine → HCID 18758312, compound

HRID 433308Notes

Reaction equation

HRID 433308 reaction equation
Cl[CH2:2][C:3]([NH:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[C:8](=[O:34])[N:9]([CH:16]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH2:32][CH3:33])[CH:24]=1)[CH2:17][C:18]([N:20]([CH3:22])[CH3:21])=[O:19])[C:10]2=[O:15])=[O:4].[CH3:35][NH:36][CH3:37].O1CCCC1>C(#N)C.C(Cl)Cl.C(=O)([O-])O.[Na+]>[CH3:35][N:36]([CH3:37])[CH2:2][C:3]([NH:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[C:8](=[O:34])[N:9]([CH:16]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH2:32][CH3:33])[CH:24]=1)[CH2:17][C:18]([N:20]([CH3:22])[CH3:21])=[O:19])[C:10]2=[O:15])=[O:4]

Participants

7

Reactant 3

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 18758349HCID 18758349, compound

Product 1

HCID 18758312HCID 18758312, compoundYield 57%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a stirred solution of 3-[4-(2-chloroacetylamino)-1,3-dioxoisoindolin-2-yl]-3-(3-ethoxy-4-methoxyphenyl)-N,N-dimethylpropanamide (1.1 g, 2.3 mmol) in acetonitrile (15 mL) was added dimethylamine in tetrahydrofuran (3.3 mL, 2 N, 6.6 mmol) at room temperature and kept for overnight. The solvent was removed in vacuo to give a solid. The solid was diluted with methylene chloride (50 mL) and sodium hydrogen carbonate (25 mL). The separated organic layer was dried over magnesium sulfate. The solvent was removed in vacuo to give a solid. The solid was purified with chromatography to give 3-{4-[2-(dimethylamino)acetylamino]-1,3-dioxoisoindolin-2-yl}-3-(3-ethoxy-4-meth-oxyphenyl)-N,N-dimethylpropanamide as a white solid (640 mg, 57% yield). To a stirred solution of 3-{4-[2-(dimethylamino)acetylamino]-1,3-dioxoisoindolin-2-yl}-3-(3-ethoxy-4-methoxyphenyl)-N,N-dimethylpropanamide in ethyl acetate (4 mL) was added hydrogen chloride in ether (2 mL, 1N, 2 mmol) at room temperature. The resulting suspension was filtered and washed ethyl acetate to give 3-{4-[2-(dimethylamino)acetylamino]-1,3-dioxoisoindolin-2-yl}-3-(3-ethoxy-4-methoxyphenyl)-N,N-dimethylpropanamide hydrogen chloride as a white solid (580 mg, 84% yield): mp, 92-94° C.; 1H NMR (DMSO-d6) δ1.30 (t, J=6.9 Hz, 3H, CH3), 2.75 (s, 3H, CH3), 2.87 (s, 6H, 2CH3), 2.98 (s, 3H, CH3), 3.21 (dd, J=5.7, 16.6 Hz, 1H, CHH), 3.61 (dd, J=9.3, 16.5 Hz, 1H, CHH), 3.72 (s, 3H, CH3), 3.98 (q, J=6.9 Hz, 2H, CH2), 4.26 (s, 2H, CH2), 5.62 (dd, J=5.6, 9.1 Hz, 1H, NCH), 6.90-6.91 (m, 2H, Ar), 7.01 (s, 1H, Ar), 7.65 (d, J=7.2 Hz, 1H, Ar), 7.85 (t, J=7.7 Hz, 1H, Ar), 8.21(d, J=8.2 Hz, 1H, Ar), 10.25 (brs, 1H, HCl), 10.56 (s, 1H, NH); 13C NMR (DMSO-d6) δ14.72, 26.37, 34.41, 34.81, 36.59, 43.34, 50.43, 55.52, 58.02, 63.78, 11.79, 112.38, 119.52, 127.79, 131.88, 131.94, 134.19, 135.79, 147.76, 148.47, 164.52, 167.25, 167.40, 169.16; Anal Calcd for C26H32N4O6+HCl+0.48 H2O: C, 57.65; H, 6.32; N, 10.34; Cl, 6.55; H2O, 1.60. Found: C, 57.70; H, 6.28; N, 10.28, Cl, 6.81; H2O, 1.61.

Workup

  1. customThe solvent was removed in vacuo
  2. customto give a solid
  3. dry with materialThe separated organic layer was dried over magnesium sulfate
  4. customThe solvent was removed in vacuo
  5. customto give a solid
  6. customThe solid was purified with chromatography

Sources & evidence

ORD record
ord-fbea1fb186f3489a8804b98120ce1855
Source dataset
uspto-grants-2003_12
Patent number
US06667316B1

Reaction notes

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