Hydrochloric Acid → 3-Ethoxy-2-hydroxy-5-(5-(3-methoxyphenyl)-2-oxo-6-(pyridin-3-yl)-1,2,3,4-tetrahydropyrimidin-4-yl)benzoic acid

HRID 401100Notes

Reaction equation

HRID 401100 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[C:22]([OH:32])=[C:23]([CH:27]=[C:28]([CH:30]=O)[CH:29]=1)[C:24]([OH:26])=[O:25])[CH3:19].[NH2:33][C:34]([NH2:36])=[O:35].Cl>C(O)C>[CH2:18]([O:20][C:21]1[C:22]([OH:32])=[C:23]([CH:27]=[C:28]([CH:30]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:29]=1)[C:24]([OH:26])=[O:25])[CH3:19]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 212616363-Ethoxy-5-formyl-2-hydroxybenzoic acid2×HCID 215581852-(3-Methoxyphenyl)-1-(3-pyridinyl)-ethanone2×

Product 1

HCID 513492173-Ethoxy-2-hydroxy-5-(5-(3-methoxyphenyl)-2-oxo-6-(pyridin-3-yl)-1,2,3,4-tetrahydropyrimidin-4-yl)benzoic acidYield 17.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 2-(3-methoxyphenyl)-1-(pyridin-3-yl)ethanone (Intermediate 69) (70 mg, 0.31 mmol), 3-ethoxy-5-formyl-2-hydroxy-benzoic acid (Intermediate 62) (65 mg, 0.31 mmol) and urea (60 mg, 1.0 mmol) in 3 mL of ethanol was added 0.2 mL of concentrated HCl, then the mixture was refluxed for 2 days. The solvent was removed and 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 135 (25 mg, yield 16.9%). 1H NMR (CD3OD 400 MHz): δ 8.73 (d, J=6.8 Hz, 1H), 8.72 (s, 1H), 8.52 (d, J=8.4 Hz, 1H), 7.50 (d, J=2.0 Hz, 1H), 7.08 (t, J=8.0 Hz, 1H), 7.01 (d, J=2.4 Hz, 1H), 7.17 (m, 3H), 6.98 (d, J=2.4 Hz, 1H), 6.74 (dd, J1=2.4 Hz, J2=8.4 Hz, 1H), 6.50 (dd, J1=2.4 Hz, J2=12.0 Hz, 2H), 5.41 (s, 1H); 4.00 (m, 2H). 3.63 (s, 3H), 1.36 (t, J=6.8 Hz, 3H); MS (ESI): m/z 462.1 [M+1]+.

Workup

  1. temperaturethe mixture was refluxed for 2 days
  2. customThe 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-ab2c23f0ccaa49cba689df6a88977be8
Source dataset
uspto-grants-2014_06
Patent number
US08741915B2

Reaction notes

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