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

HRID 2177875Notes

Reaction equation

HRID 2177875 reaction equation
[C:1]1([C:7](=O)[CH2:8][C:9]2[S:10][CH:11]=[CH:12][N: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][N: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 178870471-Phenyl-2-(thiazol-2-yl)ethanone2×

Product 1

HCID 569613444-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-phenyl-5-(thiazol-2-yl)-3,4-dihydropyrimidin-2(1H)-oneYield 3.4%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 1-phenyl-2-(thiazol-2-yl)ethanone (Intermediate 3) (170 mg, 0.84 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (212 mg, 1.00 mmol), and urea (151 mg, 2.52 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 30% of the starting materials were consumed, the reaction mixture was concentrated, and the crude product was purified by column chromatography and preparative HPLC to afford Compound 12 as a yellow solid (12.5 mg, yield: 3.4%). 1H NMR (DMSO-d6 400 MHz TMS): δ 10.25 (s, 1H), 9.25 (s, 1H), 7.82 (s, 1H), 7.50-7.56 (m, 4H), 7.48 (s, 1H), 7.36-7.40 (m, 3H), 7.22 (d, J=3.6 Hz, 1H), 5.68 (d, J=3.6 Hz, 1H), 4.10 (q, J=6.0 Hz, 2H), 1.35 (t, J=7.2 Hz, 3H); MS (ESI): m/z 439.1 [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 and preparative HPLC

Sources & evidence

ORD record
ord-12d4b45b1e7c474cb942503c567a1922
Source dataset
uspto-grants-2015_06
Patent number
US09067893B2

Reaction notes

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