Hydrochloric Acid → 2-Hydroxy-4-(2-oxo-5-phenyl-6-(pyridin-3-yl)-1,2,3,4-tetrahydropyrimidin-4-yl)benzoic acid

HRID 401117Notes

Reaction equation

HRID 401117 reaction equation
C1(C[C:8](C2C=NC=CC=2)=[O:9])C=CC=CC=1.[NH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[NH:28][C:27](=[O:29])[NH:26][CH:25]([C:30]3[CH:35]=[C:34]([N+]([O-])=O)[C:33](O)=[C:32]([O:40]CC)[CH:31]=3)[C:24]=2[C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[CH:19]C=1.NC(N)=[O:51].Cl>CCO>[OH:40][C:32]1[CH:31]=[C:30]([CH:25]2[C:24]([C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=3)=[C:23]([C:20]3[CH:19]=[N:16][CH:17]=[CH:22][CH:21]=3)[NH:28][C:27](=[O:29])[NH:26]2)[CH:35]=[CH:34][C:33]=1[C:8]([OH:9])=[O:51]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 43289002-Phenyl-1-pyridin-3-yl-ethanone2×HCID 513483616-(4-aminophenyl)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5-phenyl-3,4-dihydropyrimidin-2(1H)-one2×

Product 1

HCID 513473302-Hydroxy-4-(2-oxo-5-phenyl-6-(pyridin-3-yl)-1,2,3,4-tetrahydropyrimidin-4-yl)benzoic acidYield 12%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 2-phenyl-1-(pyridin-3-yl)ethanone (Intermediate 31) (220 mg, 1.1 mmol), methyl 4-formyl-2-hydroxybenzoate (Intermediate 84) (200 mg, 1.1 mmol), urea (198 mg, 3.3 mmol) and conc. HCl (0.2 mL) in EtOH (5 mL) was refluxed overnight. Solvent was removed in vacuo and the residue was taken up in a mixture of MeOH (10 mL) and aq. NaOH (2 M, 10 mL) and was stirred at 40° C. for 5 hours. The resulting mixture was cooled to room temperature, and then acidified with aq. HCl (2 M, 12 mL) to pH=5. Followed a standard aqueous/EtOAc workup and purified by prep-HPLC (0.1% TFA as additive) to give Compound 160 (50 mg, two steps yield 12%). 1H NMR (DMSO-d6 400 MHz): δ 8.94 (s, 1H), 8.48 (d, J=3.6 Hz, 1H), 8.40 (s, 1H), 7.76 (m, 2H), 7.65 (s, 1H), 7.42-7.38 (m, 1H), 7.06-7.00 (m, 3H), 6.93 (d, J=8.0 Hz, 1H), 6.90-6.84 (m, 3H), 5.25 (s, 1H). MS (ESI): m/z 388.2 [M+1]+.

Workup

  1. temperaturewas refluxed overnight
  2. customSolvent was removed in vacuo
  3. additionthe residue was taken up in a mixture of MeOH (10 mL) and aq. NaOH (2 M, 10 mL)
  4. temperatureThe resulting mixture was cooled to room temperature
  5. customFollowed a standard aqueous/EtOAc workup and purified by prep-HPLC (0.1% TFA as additive)

Sources & evidence

ORD record
ord-4c57f2ffbde148efa2a943b61bdd7388
Source dataset
uspto-grants-2014_06
Patent number
US08741915B2

Reaction notes

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