Hydrochloric Acid → Hydrochloric Acid

HRID 1661756Notes

Reaction equation

HRID 1661756 reaction equation
Br[CH:2]([CH3:34])[C:3]([NH:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[C:8](=[O:33])[N:9]([CH:16]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([O:30][CH2:31][CH3:32])[CH:23]=1)[CH2:17][S:18]([CH3:21])(=[O:20])=[O:19])[C:10]2=[O:15])=[O:4].[CH3:35][NH:36][CH3:37].CO.[ClH:40].CCOCC>C(#N)C.C(Cl)Cl.C(=O)([O-])O.[Na+].C(OCC)(=O)C>[CH3:35][N:36]([CH3:37])[CH:2]([CH3:34])[C:3]([NH:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[C:8](=[O:33])[N:9]([CH:16]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([O:30][CH2:31][CH3:32])[CH:23]=1)[CH2:17][S:18]([CH3:21])(=[O:20])=[O:19])[C:10]2=[O:15])=[O:4].[ClH:40]

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 674DimethylamineHCID 887MethanolHCID 3283Diethyl EtherHCID 187583882-bromo-N-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}propanamide

Product 2

HCID 313Hydrochloric AcidYield 58%HCID 187583262-(Dimethylamino)-n-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methyl-sulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}propanamide

Reagents, catalysts & solvents 4

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a suspension of 2-bromo-N-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}propanamide (500 mg, 0.9 mmol) in acetonitrile (5 mL) was added dimethylamine in methanol (1.5 mL, 2M, 3.0 mmol) at room temperature and the mixture was stirred for 2 days. The mixture was diluted with methylene chloride (50 mL) and sodium hydrogen carbonate (25 mL). The organic layer was separated, washed with brine (25 mL), and dried over magnesium sulfate. The solvent was removed in vacuo to give an oil. To a solution of the oil in ethyl acetate (20 mL) was added hydrogen chloride in ether (1.5 mL, 1N hydrogen chloride, 1.5 mmol). The resulting suspension was filtered and washed with ethyl acetate (10 mL) to give 2-(dimethylamino)-N-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}propanamide, hydrogen chloride as a white solid (290 mg, 58% yield): mp, 138-140° C.; 1H NMR (DMSO-d6) δ 1.32 (t, J=6.9 Hz, 3H, CH3), 1.56 (brs, 3H, CH3), 2.83 (brs, 6H, CH3), 3.01 (s, 3H, CH3), 3.73 (s, 3H, CH3), 4.02 (q, J=6.9 Hz, 2H, CH2), 4.15 (dd, J=4.4, 14.2 Hz, 1H, CHH), 4.27 (s, 1H, CH), 4.34 (dd, J=10.6, 14.3 Hz, 1H, CHH), 5.78 (dd, J=4.3, 10.3 Hz, 1H, NCH), 6.91-6.99 (m, 2H, Ar), 7.72 (d, J=7.1 Hz, 1H<Ar), 7.87 (d, J=7.5 Hz, 1H, Ar), 8.14 (m, 1H, Ar), 10.4 (brs, 1H, HCl), 10.71 (s, 1H, NH); 13C NMR (DMSO-d6) δ 13.42, 14.67, 41.07, 41.47, 47.31, 52.98, 55.51, 52.74, 63.84, 111.75, 112.31, 119.70, 120.16, 128.92, 129.47, 131.80, 134.05, 135.87, 147.87, 148.91, 166.66, 166.86, 167.65, 168.53; Anal Calcd for C25H31N3O7S+1.1HCl+0.6H2O: C, 52.82; H, 5.90; N, 7.39, Cl, 6.86, H2O, 1.90. Found: C, 52.57; H, 5.77; N, 7.10; Cl, 6.90; H2O, 1.47.

Workup

  1. customThe organic layer was separated
  2. washwashed with brine (25 mL)
  3. dry with materialdried over magnesium sulfate
  4. customThe solvent was removed in vacuo
  5. customto give an oil
  6. filtrationThe resulting suspension was filtered
  7. washwashed with ethyl acetate (10 mL)

Sources & evidence

ORD record
ord-6f6ac4fd89f846f88692ebc4d490b31a
Source dataset
uspto-grants-2011_10
Patent number
US08030343B2

Reaction notes

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