Hydrochloric Acid → 4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-phenyl-5-(thiophen-3-yl)-3,4-dihydropyrimidin-2(1H)-one

HRID 924776Notes

Reaction equation

HRID 924776 reaction equation
[C:1]1([C:7](=O)[CH2:8][C:9]2[CH:13]=[CH:12][S:11][CH:10]=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[CH:13]=[CH:12][S:11][CH:10]=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 122331131-Phenyl-2-(thiophen-3-yl)ethanone2×

Product 1

HCID 513473274-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-phenyl-5-(thiophen-3-yl)-3,4-dihydropyrimidin-2(1H)-oneYield 24.8%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1-phenyl-2-(thiophen-3-yl)ethanone (Intermediate 2) (100 mg, 0.50 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (100 mg, 0.47 mmol), and urea (90 mg, 1.4 mmol) in anhydrous EtOH (10 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 purified by column chromatography (EtOAc:MeOH=40:1) and preparative HPLC to afford Compound 5 as a yellow solid (51 mg, yield 24.8%). 1H NMR (DMSO-d6 400 MHz TMS): δ 10.30 (s, 1H), 8.73 (s, 1H), 7.57 (s, 1H), 7.51 (s, 1H), 7.37 (s, 3H), 7.29 (s, 3H), 7.16 (s, 1H), 6.86 (s, 1H), 6.23 (d, J=4.8 Hz, 1H), 5.21 (s, 1H), 4.10 (q, J=7.2 Hz, 2H); 1.37 (t, J=7.2 Hz, 3H); MS (ESI): m/z 438.1 [M+1]+.

Workup

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

Sources & evidence

ORD record
ord-9f13f344ecdb4c9fbdcb9aa1fd29ff71
Source dataset
uspto-grants-2016_03
Patent number
US09283229B2

Reaction notes

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