Ethyl orthoformate → 2-cyano-N-(2,4-dichloro-5-methoxyphenyl)-3-(thien-3-ylamino)prop-2-enamide

HRID 1593772

Reaction equation

HRID 1593772 reaction equation
[C:1]([CH2:3][C:4]([NH:6][C:7]1[CH:12]=[C:11]([O:13][CH3:14])[C:10]([Cl:15])=[CH:9][C:8]=1[Cl:16])=[O:5])#[N:2].[NH2:17][C:18]1[CH:22]=[CH:21][S:20][CH:19]=1.[CH2:23](OC(OCC)OCC)C>C(O)(C)C>[C:1]([C:3](=[CH:23][NH:17][C:18]1[CH:22]=[CH:21][S:20][CH:19]=1)[C:4]([NH:6][C:7]1[CH:12]=[C:11]([O:13][CH3:14])[C:10]([Cl:15])=[CH:9][C:8]=1[Cl:16])=[O:5])#[N:2]

Participants

5

Reactant 3

HCID 31214Ethyl orthoformateHCID 640543thiophen-3-amine3×HCID 160991782-cyano-N-(2,4-dichloro-5-methoxyphenyl)acetamide

Product 1

HCID 693136752-cyano-N-(2,4-dichloro-5-methoxyphenyl)-3-(thien-3-ylamino)prop-2-enamideYield 26%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a suspension of 2-cyano-N-(2,4-dichloro-5-methoxyphenyl)acetamide (1.57 g, 6.06 mmol) in 200 mL of iso-propanol was added 3-aminothiophene (600 mg, 6.06 mmol). This mixture was heated to reflux and triethylorthoformate (6.5 mL, 39.1 mmol) was added dropwise. The reaction mixture was heated at reflux overnight. Additional 3-aminothiophene (214 mg, 2.16 mmol) was added and the reaction mixture was heated at reflux for 5 hours. Additional 3-aminothiophene (100 mg, 1.01 mmol) was added and the reaction mixture was heated at reflux for 2.5 hours. The mixture was allowed to cool to room temperature and the solid was collected by filtration, washed with iso-propanol to give 572 mg (26%) of 2-cyano-N-(2,4-dichloro-5-methoxyphenyl)-3-(thien-3-ylamino)prop-2-enamide as a tan solid, mp >250° C.; MS 366.0, 368.2 (M−H)−

Workup

  1. temperatureThis mixture was heated
  2. temperatureto reflux
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux overnight
  5. temperaturethe reaction mixture was heated
  6. temperatureat reflux for 5 hours
  7. temperaturethe reaction mixture was heated
  8. temperatureat reflux for 2.5 hours
  9. filtrationthe solid was collected by filtration
  10. washwashed with iso-propanol

Sources & evidence

ORD record
ord-5a886353dd1545818b1b995b5618d85a
Source dataset
uspto-grants-2007_11
Patent number
US07297795B2

Linked notes

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