Dimethylamine → HCID 66718508, compound

HRID 433310Notes

Reaction equation

HRID 433310 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]([C@@H: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(OCC)(=O)C>[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]([C@@H: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

6

Reactant 3

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 66718514HCID 66718514, compound

Product 1

HCID 66718508HCID 66718508, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (3R)-3-[4-(2-chloroacetylamino)-1,3-dioxoisoindolin-2-yl]-3-(3-ethoxy-4-methoxyphenyl)-N,N-dimethylpropanamide (8.10 g, 16.6 mmol) and dimethylamine in tetrahydrofuran (27 mL, 2N, 54 mmol) in acetonitrile (150 mL) was stirred at room temperature overnight. The solvent was removed in vacuo to give an oil. The oil was dissolved in ethyl acetate (150 mL), washed with sodium hydrogen carbonate (2×50 mL, sat), brine (50 mL), and dried over magnesium sulfate. The solvent was removed in vacuo to give a solid. The solid was purified by column chromatography (Silica Gel, 1.5% methanol in methylene chloride) to give (3R)-3-{4-[2-(dimethylamino)acetylamino]-1,3-dioxoisoindolin-2-yl}-3-(3-ethoxy-4-methoxyphenyl)-N,N-dimethylpropanamide as a white solid (6.3 g, 76% yield). To the solid in ethyl acetate (40 mL) was added hydrogen chloride in ether (20 mL, 1N). The suspension was filtered and washed with ether to give (3R)-3-{4-[2-(dimethylamino)acetylamino]-1,3-dioxoisoindolin-2-yl}-3-(3-ethoxy-4-methoxyphenyl)-N,N-dimethylpropanamide hydrogen chloride as a yellow solid (6.4 g, 72% yield); mp, 122-124° C.; 1H NMR (DMSO-d6) δ1.33 (t, J=7 Hz, 3H, CH3), 2.75 (s, 3H, CH3), 2.89 (s, 6H, 2CH3), 2.98 (s, 3H, CH3), 3.22 (dd, J=5.4, 16.5 Hz, 1H, CHH), 3.60 (dd, J=9.2, 16.5 Hz, 1H, CHH), 3.71 (s, 3H, CH3), 3.97 (q, J=7 Hz, 2H, CH2), 4.30 (s, 2H, CH2), 5.62 (dd, J=5.6, 8.7 Hz, 1H, NCH), 6.86-6.93 (m, 2H, Ar), 7.00 (s, 1H, Ar), 7.65 (t, J=7.1 Hz, 1H, Ar), 7.84 (t, J=7.5 Hz, 1H, Ar), 8.17 (d, J=7.9 Hz, 1H, Ar), 10.49 (s, 1H, ClH), 10.64 (s, 1H, NH); 13C NMR (DMSO-d6) δ14.72, 34.41, 34.81, 36.59, 43.21, 50.43, 55.53, 57.77, 63.78, 111.79, 112.38, 119.32, 119.45, 119.58, 127.97, 131.90, 131.95, 134.12, 135.77, 147.76, 148.47, 164.28, 167.24, 167.33, 169.15; Anal Calcd for C26H32N4O6+HCl+1.1H2O: C, 56.49; H, 6.42; N, 10.13; Cl, 6.41; H2O, 3.58. Found: C, 56.33; H, 6.61; N, 9.95; H2O, 3.51.

Workup

  1. customThe solvent was removed in vacuo
  2. customto give an oil
  3. washwashed with sodium hydrogen carbonate (2×50 mL, sat), brine (50 mL)
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was removed in vacuo
  6. customto give a solid
  7. customThe solid was purified by column chromatography (Silica Gel, 1.5% methanol in methylene chloride)

Sources & evidence

ORD record
ord-a6fa529be0c8461c99bfadcdaa241949
Source dataset
uspto-grants-2003_12
Patent number
US06667316B1

Reaction notes

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