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

HRID 924906Notes

Reaction equation

HRID 924906 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-cc4ba4c8d698429fadca013c1c4f6995
Source dataset
uspto-grants-2016_03
Patent number
US09283229B2

Reaction notes

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