Diethyl (ethoxymethylene)malonate → Diethyl 2-((thiophen-3-ylamino)methylene)malonate

HRID 1947554Notes

Reaction equation

HRID 1947554 reaction equation
[NH2:1][C:2]1[CH:6]=[CH:5][S:4][C:3]=1C(OC)=O.CN1CCNCC1.CN1C(=O)CCC1.C(O[CH:28]=[C:29]([C:35]([O:37][CH2:38][CH3:39])=[O:36])[C:30]([O:32][CH2:33][CH3:34])=[O:31])C>CC#N>[S:4]1[CH:5]=[CH:6][C:2]([NH:1][CH:28]=[C:29]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:3]1

Participants

6

Reactant 4

HCID 6871Diethyl (ethoxymethylene)malonateHCID 13387N-methyl-2-pyrrolidoneHCID 531671-MethylpiperazineHCID 89652Methyl 3-amino-2-thiophenecarboxylate

Product 1

HCID 2807580Diethyl 2-((thiophen-3-ylamino)methylene)malonate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of methyl 3-aminothiophene-2-carboxylate 1 (5.0 g, 32 mmol, 1.0 eq), N-methyl piperazine (6.5 g, 64 mmol, 2.0 eq) and NMP (30 mL) was heated to reflux for 16 hours. After the decarboxylation was complete, the reaction mixture was allowed to cool to room temperature and diethyl 2-(ethoxymethylene)-malonate (7.0 g, 32 mmol, 2.0 eq) was added. The reaction mixture was heated to reflux for 4 h. The product was purified using SiO2 column chromatography (Hex/EtOAc; 100:0 to 80:20%) to obtain a light yellow powder, 5.0 g (31%). LC/MS (10-99% CH3CN/0.05% TFA gradient over 5 min): m/z 270.2, retention time 1.52 minutes. 1H NMR (DMSO-d6) δ: 10.80 (d, 1.0 H, J=13.87 Hz, NH), 8.30 (d, 1.0 H, J=13.94 Hz), 7.60 (dd, 1.0H, J=3.0 Hz, J′=2.0 Hz), 7.40 (dd, 1.0 H, J=1.5 Hz, J′=3.13 Hz), 7.28 (dd, 1.0 H, J=1.5 Hz, J′=5.2 Hz), 4.20 (q, 2H, J=7.0 Hz), 4.10 (q, 2H, J=7.0 Hz), 1.30 (m, 6H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 16 hours
  3. temperatureThe reaction mixture was heated
  4. temperatureto reflux for 4 h
  5. customThe product was purified
  6. customto obtain a light yellow powder, 5.0 g (31%)

Sources & evidence

ORD record
ord-679022f7a63d49a2a10ae9b6c4961527
Source dataset
uspto-grants-2013_03
Patent number
US08399479B2

Reaction notes

Loading…