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

HRID 401033Notes

Reaction equation

HRID 401033 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=O)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[CH2:17]([O:19][C:20]1[CH:21]=[C:22]([CH:25]=[C:26]([N+:29]([O-:31])=[O:30])[C:27]=1[OH:28])[CH:23]=O)[CH3:18].[NH2:32][C:33]([NH2:35])=[O:34].Cl>C(O)C>[CH2:17]([O:19][C:20]1[CH:21]=[C:22]([CH:23]2[C:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)=[C:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[F:1])[NH:35][C:33](=[O:34])[NH:32]2)[CH:25]=[C:26]([N+:29]([O-:31])=[O:30])[C:27]=1[OH:28])[CH3:18]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 5848783-Ethoxy-4-hydroxy-5-nitrobenzaldehydeHCID 126933791-(2-Fluorophenyl)-2-phenylethan-1-one2×

Product 1

HCID 513483604-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-(2-fluorophenyl)-5-phenyl-3,4-dihydropyrimidin-2(1H)-oneYield 39.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 1-(2-fluorophenyl)-2-phenylethanone (Intermediate 24) (100 mg, 0.47 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (92.0 mg, 0.47 mmol), and urea (85.4 mg, 1.40 mmol) in 5 mL of ethanol was added 0.2 mL of concentrated HCl solution, and the mixture was refluxed for 2 days. After the solvent was removed under reduced pressure, the residue was purified by reverse-phase preparatory HPLC (26-53% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 15 min.) to give Compound 55 (83 mg, yield 39.7%). 1H NMR (DMSO-d6 400 MHz) δ 10.25 (s, 1H), 8.77 (s, 1H), 7.48 (s, 1H), 7.43 (s, 1H), 7.29 (d, J=5.2 Hz, 1H), 7.21-7.6.80 (m, 7H), 6.79 (d, J=6.8 Hz, 2H), 5.18 (s, 1H), 4.01 (m, 2H), 1.30 (t, J=6.8 Hz, 3H); MS (ESI): m/z 450.0 [M+1]+.

Workup

  1. temperaturethe mixture was refluxed for 2 days
  2. customAfter the solvent was removed under reduced pressure
  3. customthe residue was purified by reverse-phase preparatory HPLC (26-53% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 15 min.)

Sources & evidence

ORD record
ord-d4786d96570845feaabb369f0b9adec9
Source dataset
uspto-grants-2014_06
Patent number
US08741915B2

Reaction notes

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