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

HRID 401054Notes

Reaction equation

HRID 401054 reaction equation
[C:1]1([CH2:7][C:8]([C:10]2[S:11][CH:12]=[CH:13][CH:14]=2)=O)[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.O>[CH2:15]([O:17][C:18]1[CH:19]=[C:20]([CH:21]2[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[C:8]([C:10]3[S:11][CH:12]=[CH:13][CH:14]=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

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 5848783-Ethoxy-4-hydroxy-5-nitrobenzaldehydeHCID 6870902-Phenyl-1-(2-thienyl)ethanone2×

Product 1

HCID 668261004-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5-phenyl-6-(thiophen-2-yl)-3,4-dihydropyrimidin-2(1H)-oneYield 23%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A mixture of 2-phenyl-1-(thiophen-2-yl)ethanone (Intermediate 38) (100 mg, 0.49 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (95 mg, 0.45 mmol), urea (81 mg, 1.35 mmol), and concentrated HCl solution (0.04 mL, 0.45 mmol) in EtOH (5 mL) was refluxed overnight. The mixture was diluted with water, and extracted with EtOAc. The organic layer was separated, and the aqueous layer was extracted with EtOAc. The combined organic layer was dried over Na2SO4, evaporated in vacuo, and purified by preparative HPLC to give Compound 78 (45 mg, yield 23%). 1H NMR (DMSO-d6 300 MHz): δ 10.22 (s, 1H), 8.61 (s, 1H), 7.47 (s, 1H), 7.34-7.29 (m, 2H), 7.15-7.13 (m, 1H), 7.09-7.06 (m, 3H), 6.99 (s, 1H), 6.87-6.83 (m, 3H), 5.02 (d, J=2.4 Hz, 1H), 3.92 (q, J=7.2 Hz, 2H), 1.22 (t, J=7.2 Hz, 3H); MS (ESI): m/z 438.0 [M+1]+.

Workup

  1. temperaturewas refluxed overnight
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with EtOAc
  5. dry with materialThe combined organic layer was dried over Na2SO4
  6. customevaporated in vacuo
  7. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-28d23e03f25a4e19941d64f8d2aa320b
Source dataset
uspto-grants-2014_06
Patent number
US08741915B2

Reaction notes

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