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

HRID 2177902Notes

Reaction equation

HRID 2177902 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][C:3]=1[F:17].[CH2:18]([O:20][C:21]1[CH:22]=[C:23]([CH:26]=[C:27]([N+:30]([O-:32])=[O:31])[C:28]=1[OH:29])[CH:24]=O)[CH3:19].[NH2:33][C:34]([NH2:36])=[O:35].Cl>C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:36][C:34](=[O:35])[NH:33][CH:24]([C:23]3[CH:26]=[C:27]([N+:30]([O-:32])=[O:31])[C:28]([OH:29])=[C:21]([O:20][CH2:18][CH3:19])[CH:22]=3)[C:9]=2[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][C:3]=1[F:17]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 5848783-Ethoxy-4-hydroxy-5-nitrobenzaldehydeHCID 27575671-(4-Chloro-3-fluorophenyl)-2-phenylethanone2×

Product 1

HCID 569615636-(4-chloro-3-fluorophenyl)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5-phenyl-3,4-dihydropyrimidin-2(1H)-oneYield 9.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 1-(4-chloro-3-fluorophenyl)-2-phenylethanone (Intermediate 16) (100 mg, 0.40 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (79.5 mg, 0.40 mmol), and urea (73.2 mg, 1.20 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 43 (18 mg, yield 9.3%). 1H NMR (DMSO-d6 300 MHz) δ 10.29 (s, 1H), 8.83 (s, 1H), 7.57 (s, 1H), 7.44 (m, 2H), 7.28 (d, J=9.9 Hz, 1H), 7.13-6.86 (m, 4H), 5.26 (s, 1H), 4.04 (m, 2H), 1.32 (t, J=6.3 Hz, 3H); MS (ESI): m/z 483.9 [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-1a95562e9510418d92e9e0ef667a0155
Source dataset
uspto-grants-2015_06
Patent number
US09067893B2

Reaction notes

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