Diisopropylethylamine → (E)-N-(4-(2-(dimethylamino)ethoxy)phenyl)-3-cyclopropyl-2-(4-(methoxymethoxy)phenyl)-3-phenylacrylamide

HRID 884066Notes

Reaction equation

HRID 884066 reaction equation
[CH:1]1(/[C:4](/[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:5](/[C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][O:17][CH3:18])=[CH:11][CH:10]=2)\[C:6](O)=[O:7])[CH2:3][CH2:2]1.Cl.Cl.[CH3:27][N:28]([CH3:39])[CH2:29][CH2:30][O:31][C:32]1[CH:37]=[CH:36][C:35]([NH2:38])=[CH:34][CH:33]=1.C(N(CC)C(C)C)(C)C>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:27][N:28]([CH3:39])[CH2:29][CH2:30][O:31][C:32]1[CH:37]=[CH:36][C:35]([NH:38][C:6](=[O:7])/[C:5](/[C:9]2[CH:10]=[CH:11][C:12]([O:15][CH2:16][O:17][CH3:18])=[CH:13][CH:14]=2)=[C:4](\[CH:1]2[CH2:3][CH2:2]2)/[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:34][CH:33]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 574247414-[2-(Dimethylamino)ethoxy]aniline dihydrochlorideHCID 68733087(E)-3-cyclopropyl-2-(4-(methoxymethoxy)phenyl)-3-phenylacrylic acid

Product 1

HCID 68732008(E)-N-(4-(2-(dimethylamino)ethoxy)phenyl)-3-cyclopropyl-2-(4-(methoxymethoxy)phenyl)-3-phenylacrylamideYield 100%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 7 (65 mg, 0.200 mmol), 4-(2-(dimethylamino)ethoxy)benzenamine dihydrochloride (42.6 mg, 0.168 mmol), 4-Dimethylaminopyridine (1.2 mg, 0.00982 mmol) in CH2Cl2 (3 ml) was added O-Benzotriazoyl-N,N,N′,N′-tetramethyluronium Hexafluorophosphate (83.4 mg, 0.220 mmol) under ice cooling, and the mixture was stirred at 0° C. for 10 min. Then N,N-Diisopropylethylamine (90.4 mg, 0.701 mmol) was added under ice cooling. The mixture was stirred at 0° C. for 5 min, and at room temperature for 15 h. The reaction was quenched with saturated aqueous NaHCO3 under ice cooling, and the whole was extracted with CHCl3, the organic layer was washed with brine, dried over Na2SO4, and then concentrated. Purification by silica gel flash column chromatography (eluent: CH2Cl2 to CH2Cl2/MeOH, 6:1) gave the colorless solid (100%). The solid was triturated with hexane to give 8 (80%). 8: colorless powder; 1H-NMR (CDCl3) δ 0.45 (2H, m), 0.79 (2H, m), 2.36 (6H, s), 2.55 (1H, m), 2.76 (2H, t, J=5.5 Hz), 3.41 (3H, s), 4.07 (2H, t, J=5.5 Hz), 5.05 (2H, s), 6.74 (2H, d, J=8.8 Hz), 6.88 (2H, d, J=8.8 Hz), 6.95-6.99 (4H, m), 7.10-7.20 (4H, m), 7.44 (2H, d, J=8.8 Hz).

Workup

  1. stirringThe mixture was stirred at 0° C. for 5 min
  2. waitat room temperature for 15 h
  3. customThe reaction was quenched with saturated aqueous NaHCO3 under ice cooling
  4. extractionthe whole was extracted with CHCl3
  5. washthe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customPurification by silica gel flash column chromatography (eluent: CH2Cl2 to CH2Cl2/MeOH, 6:1)

Sources & evidence

ORD record
ord-6ffaef9642b04170a286866e1a495b08
Source dataset
uspto-grants-2012_08
Patent number
US08236987B2

Reaction notes

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