Cyanoacetamide → HCID 2408012, compound

HRID 1959103Notes

Reaction equation

HRID 1959103 reaction equation
[C:1]([CH2:3][C:4]([NH2:6])=[O:5])#[N:2].[H-].[Na+].[CH3:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]=[C:18]=[S:19])=[CH:13][CH:12]=1.Br[CH2:21][C:22]([C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=1)=[O:23].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[NH2:2][C:1]1[C:3]([C:4]([NH2:6])=[O:5])=[C:18]([NH:17][C:14]2[CH:13]=[CH:12][C:11]([O:10][CH3:9])=[CH:16][CH:15]=2)[S:19][C:21]=1[C:22](=[O:23])[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=1

Participants

8

Reactant 5

HCID 7898CyanoacetamideHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 68303p-Chlorophenacyl bromideHCID 752934-Methoxyphenyl isothiocyanate

Product 1

HCID 2408012HCID 2408012, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 2-cyanoacetamide (3.0 g, 36 mmol) in DMF (50 mL) was added sodium hydride (60% in mineral oil, 1.43 g, 35.7 mmol, 1 eq.), and the mixture stirred at 0° C. for 1 hour, giving a clear solution. 4-Methoxyphenyl isothiocyanate (15.90 g, 35.7 mmol, 1 eq.) in DMF (10 mL) was added, and stirred for 30 minutes, then 2-bromo-4′-chloroacetophenone (8.33 g, 35.7 mmol, 1 eq.) and potassium carbonate (4.93 g, 35.7 mmol, 1 eq.) were added, and the mixture was stirred at room temperature for 1 week. Water (200 mL) was added; and the dark precipitate that formed was filtered, washed with water (3×50 mL), ethyl acetate (3×15 mL), and acetone (3×15 mL), then dried under vacuum to give 4-amino-5-(4-chlorobenzoyl)-2-[(4-methoxyphenyl)amino]thiophene-3-carboxamide (5.6 g) as a light orange solid. 1H NMR (DMSO-d6): δ 9.97 (1H, s), 8.03 (2H, s), 7.54 (2H, d, J=8.2 Hz), 7.48 (2H, d, J=8.2 Hz), 7.41 (2H, s), 7.25 (2H, d, J=8.6 Hz), 6.94 (2H, d, J=8.6 Hz), 3.74 (3H, s).

Workup

  1. customgiving a clear solution
  2. stirringstirred for 30 minutes
  3. stirringthe mixture was stirred at room temperature for 1 week
  4. customand the dark precipitate that formed
  5. filtrationwas filtered
  6. washwashed with water (3×50 mL), ethyl acetate (3×15 mL), and acetone (3×15 mL)
  7. customdried under vacuum

Sources & evidence

ORD record
ord-e01818fae7f9408ea8b71b9552a4c73d
Source dataset
uspto-grants-2013_04
Patent number
US08410163B2

Reaction notes

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