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

HRID 401117

反応式

HRID 401117 の反応式
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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
40 °C

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-4c57f2ffbde148efa2a943b61bdd7388
出典データセット
uspto-grants-2014_06
特許番号
US08741915B2

関連ノート

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