1-Hydroxybenzotriazole → (E)-N-(4-(2-(dimethylamino)ethoxy)phenyl)-2-(4-(methoxymethoxy)phenyl)-3-phenylpent-2-enamide

HRID 884051Notes

Reaction equation

HRID 884051 reaction equation
[CH3:1][O:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8](/[C:11](=[C:15](\[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)/[CH2:16][CH3:17])/[C:12]([OH:14])=O)=[CH:7][CH:6]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.Cl.Cl.[CH3:48][N:49]([CH3:60])[CH2:50][CH2:51][O:52][C:53]1[CH:58]=[CH:57][C:56]([NH2:59])=[CH:55][CH:54]=1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH3:48][N:49]([CH3:60])[CH2:50][CH2:51][O:52][C:53]1[CH:58]=[CH:57][C:56]([NH:59][C:12](=[O:14])/[C:11](/[C:8]2[CH:9]=[CH:10][C:5]([O:4][CH2:3][O:2][CH3:1])=[CH:6][CH:7]=2)=[C:15](/[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)\[CH2:16][CH3:17])=[CH:55][CH:54]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 574247414-[2-(Dimethylamino)ethoxy]aniline dihydrochlorideHCID 57693045(E)-2-(4-(methoxymethoxy)phenyl)-3-phenylpent-2-enoic acid

Product 1

HCID 57693048(E)-N-(4-(2-(dimethylamino)ethoxy)phenyl)-2-(4-(methoxymethoxy)phenyl)-3-phenylpent-2-enamideYield 43%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Method A; To a mixture of 3 (2.50 g, 8.00 mmol), EDC.HCl (1.84 g, 9.60 mmol) and HOBt (1.30 g, 9.62 mmol) in DMF (50 ml) was added a solution of 4-(2-(dimethylamino)ethoxy)benzene-amine dihydrochloride (2.23 g, 8.81 mmol) and N,N-Diisopropylethylamine (4.13 g, 32.0 mmol) under ice cooling, and the mixture was stirred at room temperature for 18 h. The reaction was quenched with saturated aqueous NaHCO3 under ice cooling, and the whole was extracted with AcOEt, the organic layer was washed with H2O×2, brine, dried over Na2SO4, then concentrated. Purification by silica gel flash column chromatography (eluent: AcOEt then CHCl3/MeOH, 10:1) and recystallization from AcOEt-hexanes gave 4 (43%). 4: colorless powder; 1H-NMR (CDCl3) δ 1.05 (3H, t, J=7.4), 2.33 (6H, s), 2.71 (2H, t, J=5.7 Hz), 2.77 (2H, q, J=7.4 Hz), 3.43 (3H, s), 4.04 (2H, t, J=5.7 Hz), 5.09 (2H, s), 6.78 (2H, d, J=8.8 Hz), 6.88 (2H, d, J=9.0 Hz), 7.00 (2H, d, J=8.8 Hz), 7.00 (1H, brs) 7.06 (2H, m), 7.12-7.23 (3H, m), 7.41 (2H, d, J=9.0 Hz).

Workup

  1. customThe reaction was quenched with saturated aqueous NaHCO3 under ice cooling
  2. extractionthe whole was extracted with AcOEt
  3. washthe organic layer was washed with H2O×2, brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customPurification by silica gel flash column chromatography (eluent

Sources & evidence

ORD record
ord-bc299933f7484bfdadf46150470272e5
Source dataset
uspto-grants-2012_08
Patent number
US08236987B2

Reaction notes

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