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

HRID 401053Notes

Reaction equation

HRID 401053 reaction equation
[CH2:1]([O:3][C:4]1[C:5]([OH:15])=[C:6]([CH:10]=[C:11]([CH:13]=O)[CH:12]=1)[C:7]([OH:9])=[O:8])[CH3:2].[C:16]1([C:22](=O)[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[NH2:31][C:32]([NH2:34])=[O:33].Cl>CCO.CO.CCOC(C)=O>[CH2:1]([O:3][C:4]1[C:5]([OH:15])=[C:6]([CH:10]=[C:11]([CH:13]2[C:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[C:22]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[NH:34][C:32](=[O:33])[NH:31]2)[CH:12]=1)[C:7]([OH:9])=[O:8])[CH3:2]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 99482-PhenylacetophenoneHCID 212616363-Ethoxy-5-formyl-2-hydroxybenzoic acid2×

Product 1

HCID 513486643-Ethoxy-2-hydroxy-5-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoic acidYield 5.8%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 3-ethoxy-5-formyl-2-hydroxybenzoic acid (Intermediate 37) (130 mg, 0.60 mmol), 1,2-diphenylethanone (150 mg, 0.76), and urea (80 mg, 1.3 mmol) in anhydrous EtOH (5 mL) was added concentrated HCl solution (0.2 mL), the reaction mixture was refluxed overnight. TLC (EtOAc:MeOH=10:1) showed about 50% of the starting materials were consumed. The reaction mixture was concentrated, and purified by column chromatograph (EtOAc:MeOH=40:1) and preparative HPLC to afford Compound 77 as a yellow solid (15 mg, yield: 5.6%). 1H NMR (DMSO-d6 400 MHz): δ 11.37 (s, 1H), 8.66 (s, 1H), 7.47 (s, 1H), 7.43 (d, J=2.0 Hz, 1H), 7.25-7.27 (m, 3H), 7.21-7.25 (m, 2H), 7.14 (d, J=2.0 Hz, 1H), 6.97-7.05 (m, 3H), 6.81 (d, J=2.4 Hz, 2H), 5.10 (d, J=2.8 Hz, 1H), 3.97-4.02 (m, 2H), 1.31 (t, J=6.8 Hz, 3H); MS (ESI): m/z 431.1 [M+1]+.

Workup

  1. temperaturethe reaction mixture was refluxed overnight
  2. customwere consumed
  3. concentrationThe reaction mixture was concentrated
  4. custompurified by column chromatograph (EtOAc:MeOH=40:1) and preparative HPLC

Sources & evidence

ORD record
ord-7d1a0a707f05406097eea3a1998b7f79
Source dataset
uspto-grants-2014_06
Patent number
US08741915B2

Reaction notes

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