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

HRID 401087

Reaction equation

HRID 401087 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([C:7](=O)[CH2:8][C:9]2[CH:13]=[CH:12][S:11][CH:10]=2)=[N:3]1.[OH:15][C:16]1[C:23]([N+:24]([O-:26])=[O:25])=[CH:22][C:19]([CH:20]=O)=[CH:18][C:17]=1[O:27][CH3:28].[NH2:29][C:30]([NH2:32])=[O:31].Cl.[CH3:34]CO>>[CH2:28]([O:27][C:17]1[CH:18]=[C:19]([CH:20]2[C:8]([C:9]3[CH:13]=[CH:12][S:11][CH:10]=3)=[C:7]([C:4]3[CH:5]=[CH:6][N:2]([CH3:1])[N:3]=3)[NH:32][C:30](=[O:31])[NH:29]2)[CH:22]=[C:23]([N+:24]([O-:26])=[O:25])[C:16]=1[OH:15])[CH3:34]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 702EthanolHCID 1176UreaHCID 811345-NitrovanillinHCID 651950761-(1-methyl-1H-pyrazol-3-yl)-2-(thiophen-3-yl)ethanone2×

Product 1

HCID 513490824-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-(1-methyl-1H-pyrazol-3-yl)-5-(thiophen-3-yl)-3,4-dihydropyrimidin-2(1H)-oneYield 81%

Procedure

A mixture of 1-(1-methyl-1H-pyrazol-3-yl)-2-(thiophen-3-yl)ethanone (Intermediate 58) (750 mg, 3.6 mmol), 4-hydroxy-3-methoxy-5-nitrobenzaldehyde (782 mg, 3.7 mmol), urea (666 mg, 11.1 mmol) and conc. HCl (0.2 mL) in EtOH (10 mL) was refluxed overnight. The mixture was concentrated under reduced pressure to dryness and purified by prep-HPLC (0.1% TFA as additive) to give Compound 119 (1.3 g, yield 81%). 1H NMR and MS (ESI) characterization included for the individual enantiomers, see Compound 149 and Compound 150.

Workup

  1. temperaturewas refluxed overnight
  2. concentrationThe mixture was concentrated under reduced pressure to dryness
  3. custompurified by prep-HPLC (0.1% TFA as additive)

Sources & evidence

ORD record
ord-ddd4191c03bf4694b408aad1997bc684
Source dataset
uspto-grants-2014_06
Patent number
US08741915B2

Linked notes

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