Dimethylamine → HCID 18758365, compound

HRID 433311Notes

Reaction equation

HRID 433311 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[C:6]([C:11]3[NH:12][CH:13]=[CH:14][CH:15]=3)[CH:7]=[CH:8][CH:9]=2)[C:4](=[O:16])[N:3]1[CH:17]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([O:30][CH2:31][CH3:32])[CH:23]=1)[CH2:18][C:19](O)=[O:20].[C:33](N1C=CN=C1)([N:35]1C=CN=[CH:36]1)=O.CNC.O>O1CCCC1.C(Cl)Cl>[O:1]=[C:2]1[C:10]2[C:5](=[C:6]([C:11]3[NH:12][CH:13]=[CH:14][CH:15]=3)[CH:7]=[CH:8][CH:9]=2)[C:4](=[O:16])[N:3]1[CH:17]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([O:30][CH2:31][CH3:32])[CH:23]=1)[CH2:18][C:19]([N:35]([CH3:36])[CH3:33])=[O:20]

Participants

7

Reactant 4

HCID 674DimethylamineHCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 18758357HCID 18758357, compound

Product 1

HCID 18758365HCID 18758365, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of 3-(1,3-dioxo-4-pyrrolylisoindolin-2-yl)-3-(3-ethoxy-4-methoxy-phenyl)propanoic acid (1.29 g, 2.97 mmol), and carbonyldiimidazole (481 mg, 2.97 mmol) in tetrahydrofuran (13 mL) was stirred at room temperature for 2 h. To the mixture was added dimethylamine in tetrahydrofuran (1.7 mL, 2N, 3.4 mmol) and the mixture stirred for an additional 2 h. Water (70 mL) and methylene chloride (50 mL) was added to the mixture. The organic layer was separated, washed with brine (20 mL), and dried over magnesium sulfate. The solvent was removed in vacuo to give a brown solid. This solid was purified by column chromatography (silica gel, 1:5 ethyl acetate:methylene chloride+0.1% MeOH) to give 3-(1,3-dioxo-4-pyrrolylisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)-N,N-dimethylpropanamide as a yellow solid (750 mg, 55% yield): mp, 105-107° C.; 1H NMR (CDCl3) δ1.43 (t, J=7 Hz, 3H, CH3), 2.88 (s, 3H, CH3), 3.00 (s, 3H, 2CH3), 3.04 (dd, J=4.9, 16 Hz, 1H, CHH), 3.82 (s, 3H, CH3), 3.91 (dd, J=10.2, 16.6 Hz, 1H, CHH), 4.09 (q, J=7 Hz, 2H, CH2), 5.82 (dd, J=4.9, 10.2 Hz, 1H, NCH), 6.35 (t, J=2 Hz, 2H, Ar),6.77-6.81 (m, 1H, Ar), 7.11-7.15 (m, 4H, Ar), 7.52-7.56 (m, 1H, Ar), 7.63-7.71 (m, 2H, Ar); 13C NMR (CDCl3) δ14.65, 34.71, 35.34, 37.02, 51.52, 55.83, 64.32, 110.48, 111.22, 112.76, 120.24, 120.66, 121.35, 122.02, 129.75, 132.00, 134.06, 134.94, 138.23, 148.15, 148.93, 166.19, 167.34, 169.58; Anal Calcd for C26H27N3O5+0.15 H2O: C, 67.30; H, 5.99; N, 8.85. Found: C, 67.16; H, 5.88; N, 8.92.

Workup

  1. stirringthe mixture stirred for an additional 2 h
  2. customThe organic layer was separated
  3. washwashed with brine (20 mL)
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was removed in vacuo
  6. customto give a brown solid
  7. customThis solid was purified by column chromatography (silica gel, 1:5 ethyl acetate:methylene chloride+0.1% MeOH)

Sources & evidence

ORD record
ord-99586ff30b49435bb22135e5bea288b6
Source dataset
uspto-grants-2003_12
Patent number
US06667316B1

Reaction notes

Loading…