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

HRID 401099Notes

Reaction equation

HRID 401099 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:9][C:10]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=O)[CH:6]=[CH:7][CH:8]=1.[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>[CH2:18]([O:20][C:21]1[CH:22]=[C:23]([CH:24]2[C:9]([C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=3)=[C:10]([C:12]3[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=3)[NH:36][C:34](=[O:35])[NH:33]2)[CH:26]=[C:27]([N+:30]([O-:32])=[O:31])[C:28]=1[OH:29])[CH3:19]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 5848783-Ethoxy-4-hydroxy-5-nitrobenzaldehydeHCID 215581852-(3-Methoxyphenyl)-1-(3-pyridinyl)-ethanone2×

Product 1

HCID 569615134-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5-(3-methoxyphenyl)-6-(pyridin-3-yl)-3,4-dihydropyrimidin-2(1H)-oneYield 25%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 2-(3-methoxyphenyl)-1-(pyridin-3-yl)ethanone (Intermediate 69) (60 mg, 0.26 mmol), 3-ethoxy-4-hydroxy-5-nitro-benzaldehyde (55.8 mg, 0.26 mmol) and urea (46.8 mg, 0.78 mmol) in 3 mL of ethanol was added 0.2 mL of concentrated HCl. The mixture was refluxed for 2 days. After the solvent was removed, 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 134 (30 mg, yield 24.6%). 1H NMR (CD3OD 400 MHz): δ 8.75 (s, 1H), 8.55 (d, J=8.0 Hz, 1H), 8.01 (dd, J1=6.0 Hz, J2=8.4 Hz, 1H), 7.60 (d, J=2.0 Hz, 1H), 7.08 (m, 2H), 6.75 (dd, J1=2.4 Hz, J2=8.4 Hz, 1H), 6.55 (s, 1H), 6.49 (d, J=3.6 Hz, 1H), 5.53 (s, 1H), 4.02 (m, 2H), 3.64 (s, 3H); 1.39 (t, J=6.8 Hz, 3H); MS (ESI): m/z 463.1 [M+1]+.

Workup

  1. temperatureThe mixture was refluxed for 2 days
  2. customAfter the solvent was removed
  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-b876a565093547099ff4ed69b07b722c
Source dataset
uspto-grants-2014_06
Patent number
US08741915B2

Reaction notes

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