Ethyl cyanoacetate → Ethyl 2-amino-4-(3,4,5-trimethoxyphenyl)-3-thiophenecarboxylate

HRID 602838노트

반응식

HRID 602838 반응식
[C:1]([CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2].[CH3:9][O:10][C:11]1[CH:12]=[C:13]([C:21](=O)[CH3:22])[CH:14]=[C:15]([O:19][CH3:20])[C:16]=1[O:17][CH3:18].N1CCOCC1.BrC1C=CC2OC(C(NC3[S:43]C=C(C4C=CC(Cl)=CC=4)C=3C(O)=O)=O)=NC=2C=1>C1(C)C=CC=CC=1>[NH2:2][C:1]1[S:43][CH:22]=[C:21]([C:13]2[CH:12]=[C:11]([O:10][CH3:9])[C:16]([O:17][CH3:18])=[C:15]([O:19][CH3:20])[CH:14]=2)[C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5]

참가 물질

6

반응물 4

HCID 7764Ethyl cyanoacetateHCID 8083MorpholineHCID 143453',4',5'-TrimethoxyacetophenoneHCID 595359892-(5-Bromobenzo[d]oxazole-2-carboxamido)-4-(4-chlorophenyl)thiophene-3-carboxylic acid

생성물 1

HCID 299299Ethyl 2-amino-4-(3,4,5-trimethoxyphenyl)-3-thiophenecarboxylate

시약·촉매·용매 1

HCID 1140Toluene용매

반응 조건

온도
80 °C

실험 절차

Ethyl cyanoacetate (5 mmol), and 1-(3,4,5-trimethoxyphenyl)ethanone (5 mmol) are dissolved in toluene (5 mL). Morpholine (5 mmol) is added followed by activated molecular sieves (4A). The reaction is stirred at 80° C. for 12 hours. The reaction is cooled to room temperature, filtered and concentrated. The residue is taken up in toluene (5 mL), ethanol (5 mL) and sulfur is added (0.16 g; 5 mmol). The reaction mixture is heated with mixing at 70° C. for 12 hours. The reaction is cooled to room temperature and the solvents are evaporated. The residue is purified by HPLC to provide ethyl 2-amino-4-(3,4,5-trimethoxyphenyl)thiophene-3-carboxylate. Ethyl 2-amino-4-(3,4,5-trimethoxyphenyl)thiophene-3-carboxylate (5 mmol) is treated with 4-methylbenzoyl chloride (5 mmol) in THF (10 mL). The reaction is stirred at room temperature for 10 hours. The reaction is diluted with 1N NaOH (10 mL) and ethyl acetate (15 mL). The layers are separated, the organic layer is dried with anhydrous sodium sulfate, filtered and concentrated. The residue is purified by flash chromatography to provide ethyl 4-p-tolyl-2-(3,4,5-trimethoxybenzamido)thiophene-3-carboxylate. Ethyl 4-p-tolyl-2-(3,4,5-trimethoxybenzamido)thiophene-3-carboxylate is hydrolyzed under a variety of conditions (e.g. LiOH, water; LiOH, H2O2, water; or NaOH, water) to provide the title compound

후처리

  1. temperatureThe reaction is cooled to room temperature
  2. filtrationfiltered
  3. concentrationconcentrated
  4. additionethanol (5 mL) and sulfur is added (0.16 g; 5 mmol)
  5. temperatureThe reaction mixture is heated
  6. additionwith mixing at 70° C. for 12 hours
  7. temperatureThe reaction is cooled to room temperature
  8. customthe solvents are evaporated
  9. customThe residue is purified by HPLC

출처 및 근거

ORD 기록
ord-32a0306b14bf4ac6adaa8e2991eedb4c
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07906553B2

반응 노트

불러오는 중…