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

HRID 2177968Notes

Reaction equation

HRID 2177968 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7](=O)[CH2:8][C:9]2[CH:13]=[CH:12][S:11][CH:10]=2)[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>[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:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=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

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 5848783-Ethoxy-4-hydroxy-5-nitrobenzaldehydeHCID 610560411-(Pyridin-3-yl)-2-(thiophen-3-yl)ethanone2×

Product 1

HCID 668258884-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-(pyridin-3-yl)-5-(thiophen-3-yl)-3,4-dihydropyrimidin-2(1H)-oneYield 33%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 1-(pyridin-3-yl)-2-(thiophen-3-yl)ethanone (Intermediate 56) (100 mg, 0.492 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (94 mg, 0.45 mmol), urea (81 mg, 1.34 mmol), concentrated HCl (0.04 mL, 0.45 mmol) in EtOH (5 mL) was refluxed overnight. Then the mixture was evaporated in vacuo and the residue was purified by preparative HPLC to give Compound 116 (65 mg, yield 33%). 1H NMR (DMSO-d6 400 MHz): δ 10.30 (s, 1H), 8.92 (s, 1H), 8.56-8.54 (m, 1H), 8.46-8.44 (m, 1H), 7.77 (d, J=8.0 Hz, 1H), 7.63 (s, 1H), 7.48-7.43 (m, 2H), 7.25-7.22 (m, 2H), 6.94 (s, 1H), 6.35 (d, J=5.2 Hz, 1H), 5.27 (d, J=2.8 Hz, 1H), 4.12-4.04 (m, 2H), 1.35 (t, J=6.8 Hz, 3H); MS (ESI): 438.9 m/z [M+1]+.

Workup

  1. temperaturewas refluxed overnight
  2. customThen the mixture was evaporated in vacuo
  3. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-1c54027d036146f59e8fd3b0c9d08516
Source dataset
uspto-grants-2015_06
Patent number
US09067893B2

Reaction notes

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