Hydrochloric Acid → HCID 66718495, compound

HRID 2282978Notes

Reaction equation

HRID 2282978 reaction equation
[CH3:1][N:2]([CH3:36])[CH2:3][C:4]([NH:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[C:9](=[O:35])[N:10]([CH:17]([C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[C:26]([O:32][CH2:33][CH3:34])[CH:25]=1)[CH2:18][C:19]([N:21]([CH3:23])[CH3:22])=[O:20])[C:11]2=[O:16])=[O:5].[ClH:37].CCOCC>C(OCC)(=O)C>[ClH:37].[CH3:36][N:2]([CH3:1])[CH2:3][C:4]([NH:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[C:9](=[O:35])[N:10]([CH:17]([C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[C:26]([O:32][CH2:33][CH3:34])[CH:25]=1)[CH2:18][C:19]([N:21]([CH3:22])[CH3:23])=[O:20])[C:11]2=[O:16])=[O:5]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 18758312HCID 18758312, compound

Product 1

HCID 66718495HCID 66718495, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

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-methoxyphenyl)-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) δ 1.30 (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+0.48H2O: 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. filtrationThe resulting suspension was filtered
  2. washwashed ethyl acetate

Sources & evidence

ORD record
ord-a667bda0a9d24bf8aa0f280b6f7d4328
Source dataset
uspto-grants-2015_09
Patent number
USRE045685E1

Reaction notes

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