Malononitrile → HCID 49763815, compound

HRID 1959102Notes

Reaction equation

HRID 1959102 reaction equation
[C:1](#[N:5])[CH2:2][C:3]#[N:4].C(=O)([O-])[O-].[K+].[K+].[CH2:12]([O:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]=[C:22]=[S:23])=[CH:17][CH:16]=1)[CH3:13].Br[CH2:25][C:26]([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][C:29]=1[O:36][CH3:37])=[O:27]>CN(C)C=O>[NH2:4][C:3]1[C:2]([C:1]#[N:5])=[C:22]([NH:21][C:18]2[CH:19]=[CH:20][C:15]([O:14][CH2:12][CH3:13])=[CH:16][CH:17]=2)[S:23][C:25]=1[C:26](=[O:27])[C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][C:29]=1[O:36][CH3:37]

Participants

6

Reactant 4

HCID 8010MalononitrileHCID 11430Potassium CarbonateHCID 77006p-Ethoxyphenyl isothiocyanateHCID 986832-Bromo-1-(2,4-dimethoxyphenyl)ethanone

Product 1

HCID 49763815HCID 49763815, compoundYield 85.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of malononitrile (0.40 g, 6.1 mmol) in dimethylformamide (DMF) (5 mL) was added potassium carbonate (1.68 g, 12.2 mmol, 2 eq.). The mixture was stirred at room temperature for 15 minutes, and 4-ethoxyphenyl isothiocyanate (1.07 g, 6.1 mmol) was added. After stirring for an additional 30 minutes, 2-bromo-2′,4′-dimethoxy-acetophenone (1.57 g, 6.1 mmol, 1 eq.) was added, and the mixture stirred at room temperature overnight. The solvent was removed under reduced pressure, and water (20 mL) was added to the residue. The resulting solid was collected by filtration and dried under vacuum to give 2.80 g of crude product as a yellow solid. This crude product was combined with two similar batches (altogether totaling 7.7 g of crude product) and purified by silica gel column chromatography, eluting with hexane/ethyl acetate (2:1 then 1:1) to give 4-amino-5-(2,4-dimethoxybenzoyl)-2-[(4-ethoxyphenyl)amino]thiophene-3-carbonitrile (2.2 g) as a yellow-brown solid. 1H NMR (DMSO-d6): δ 10.24 (1H, s), 7.79 (2H, br.s), 7.21 (2H, d, J=8.6 Hz), 7.09 (1H, d, J=8.6 Hz), 6.91 (2H, d, J=9.0 Hz), 6.56 (1H, d, J=2.0 Hz), 6.49 (1H, dd, J=8.4 Hz, J=2.2 Hz), 4.02-3.96 (2H, q, J=7.0 Hz), 3.76 (3H, s), 1.92-1.57 (3H, t, J=7.0 Hz).

Workup

  1. stirringAfter stirring for an additional 30 minutes
  2. stirringthe mixture stirred at room temperature overnight
  3. customThe solvent was removed under reduced pressure, and water (20 mL)
  4. additionwas added to the residue
  5. filtrationThe resulting solid was collected by filtration
  6. customdried under vacuum
  7. customto give 2.80 g of crude product as a yellow solid
  8. custompurified by silica gel column chromatography
  9. washeluting with hexane/ethyl acetate (2:1

Sources & evidence

ORD record
ord-76d6af3bff0c4f53964379512ea65a64
Source dataset
uspto-grants-2013_04
Patent number
US08410163B2

Reaction notes

Loading…