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

HRID 401037

Reaction equation

HRID 401037 reaction equation
[C:1]1([C:7](=O)[CH2:8][C:9]2[CH:14]=[N:13][CH:12]=[CH:11][N:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:16]([O:18][C:19]1[CH:20]=[C:21]([CH:24]=[C:25]([N+:28]([O-:30])=[O:29])[C:26]=1[OH:27])[CH:22]=O)[CH3:17].[NH2:31][C:32]([NH2:34])=[O:33].Cl>C(O)C>[CH2:16]([O:18][C:19]1[CH:20]=[C:21]([CH:22]2[C:8]([C:9]3[CH:14]=[N:13][CH:12]=[CH:11][N:10]=3)=[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[NH:34][C:32](=[O:33])[NH:31]2)[CH:24]=[C:25]([N+:28]([O-:30])=[O:29])[C:26]=1[OH:27])[CH3:17]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 5209771-Phenyl-2-pyrazin-2-yl ethanone2×HCID 5848783-Ethoxy-4-hydroxy-5-nitrobenzaldehyde

Product 1

HCID 513483624-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-phenyl-5-(pyrazin-2-yl)-3,4-dihydropyrimidin-2(1H)-oneYield 21.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 1-phenyl-2-(pyrazin-2-yl)ethanone (Intermediate 26) (150 mg, 0.76 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (149 mg, 0.76 mmol), and urea (137 mg, 2.28 mmol) in 20 mL of ethanol was added 0.2 mL of concentrated HCl solution, the reaction mixture was stirred at reflux 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 58 (72 mg, yield 21.9%). 1H NMR (DMSO-d6 300 MHz): δ 10.27 (S, 1H), 9.22 (s, 1H), 8.43 (s, 1H), 8.15 (s, 1H), 7.84 (s, 1H), 7.65 (s, 1H), 7.44 (m, 4H), 7.32 (d, J=7.2 Hz, 3H), 5.45 (d, J=2.1 Hz, 1H), 4.10 (m, 2H), 1.35 (t, J=6.9 Hz, 3H); MS (ESI): m/z 434.0 [M+1]+.

Workup

  1. temperatureat reflux 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-23a2b1015c11469ebcee6230f6ee372f
Source dataset
uspto-grants-2014_06
Patent number
US08741915B2

Linked notes

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