Hydrochloric Acid → HCID 51347326, compound

HRID 924775Notes

Reaction equation

HRID 924775 reaction equation
[C:1]1([C:7](=O)[CH2:8][C:9]2[S:10][CH:11]=[CH:12][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:15]([O:17][C:18]1[CH:19]=[C:20]([CH:23]=[C:24]([N+:27]([O-:29])=[O:28])[C:25]=1[OH:26])[CH:21]=O)[CH3:16].[NH2:30][C:31]([NH2:33])=[O:32].Cl>CCO.CO.CCOC(C)=O>[CH2:15]([O:17][C:18]1[CH:19]=[C:20]([CH:21]2[C:8]([C:9]3[S:10][CH:11]=[CH:12][CH:13]=3)=[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[NH:33][C:31](=[O:32])[NH:30]2)[CH:23]=[C:24]([N+:27]([O-:29])=[O:28])[C:25]=1[OH:26])[CH3:16]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 5848783-Ethoxy-4-hydroxy-5-nitrobenzaldehydeHCID 2737595HCID 2737595, compound

Product 1

HCID 51347326HCID 51347326, compoundYield 6.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1-phenyl-2-(thiophen-2-yl)ethanone (Intermediate 1, see Example 178 for synthesis of all Intermediates) (200 mg, 0.99 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (200 mg, 0.94 mmol), and urea (175 mg, 2.82 mmol) in anhydrous EtOH (20 mL) was added concentrated HCl solution (0.1 mL), and the reaction mixture was refluxed for three days. When TLC (EtOAc:MeOH=10:1) showed that about 50% of starting materials were consumed, the reaction mixture was concentrated, and the crude product was purified by column chromatography (EtOAc:MeOH=40:1) and preparative HPLC to afford Compound 4 as a yellow solid (27 mg, yield 6.2%). 1H NMR (DMSO-d6 400 MHz): δ 10.30 (s, 1H), 8.89 (s, 1H), 7.65 (s, 1H), 7.53 (s, 1H), 7.40 (s, 3H), 7.34 (s, 3H), 7.10 (d, J=5.2 Hz, 1H), 6.71-6.73 (m, 1H), 6.56 (s, 1H), 5.24 (s, 1H), 4.10 (q, J=7.2 Hz, 2H); 1.37 (t, J=7.2 Hz, 3H); MS (ESI): m/z 438.2 [M+1]+.

Workup

  1. temperaturethe reaction mixture was refluxed for three days
  2. customwere consumed
  3. concentrationthe reaction mixture was concentrated
  4. customthe crude product was purified by column chromatography (EtOAc:MeOH=40:1) and preparative HPLC

Sources & evidence

ORD record
ord-fa43faa77e7247ea859eddf6654b9a4b
Source dataset
uspto-grants-2016_03
Patent number
US09283229B2

Reaction notes

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