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

HRID 401117

Reaktionsgleichung

Reaktionsgleichung von HRID 401117
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]

Komponenten

6

Edukt 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×

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

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]+.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-4c57f2ffbde148efa2a943b61bdd7388
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08741915B2

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