Hydrochloric Acid → 2-hydroxy-4-(6-(1-methyl-1H-pyrazol-4-yl)-2-oxo-5-phenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoic acid

HRID 401124ノート

反応式

HRID 401124 の反応式
[CH3:1][N:2]1[CH:6]=[C:5]([C:7](=O)[CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:4]=[N:3]1.NC1C=CC(C2[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=2C2C=CC=CC=2)=CC=1.N[C:50](N)=[O:51].Cl.CC[OH:56]>>[OH:40][C:32]1[CH:31]=[C:30]([CH:25]2[C:8]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)=[C:7]([C:5]3[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=3)[NH:28][C:27](=[O:29])[NH:26]2)[CH:35]=[CH:34][C:33]=1[C:50]([OH:51])=[O:56]

参加物

6

反応物 5

HCID 313Hydrochloric AcidHCID 702EthanolHCID 1176UreaHCID 155619131-(1-methyl-1H-pyrazol-4-yl)-2-phenylethanone2 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 668257572-hydroxy-4-(6-(1-methyl-1H-pyrazol-4-yl)-2-oxo-5-phenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoic acid収率 20%

反応条件

温度
60 °C

実験手順

A mixture of 1-(1-methyl-1H-pyrazol-4-yl)-2-phenylethanone (Intermediate 88) (150 mg, 0.75 mmol), methyl 4-formyl-2-hydroxybenzoate (Intermediate 84) (135 mg, 0.75 mmol), urea (138 mg, 2.3 mmol) and conc. HCl (0.5 mL) in EtOH (5 mL) was refluxed under N2 atmosphere overnight. The mixture was concentrated under reduced pressure. The residue was taken up in MeOH (10 mL) and aq. NaOH (2 M, 10 mL) and was stirred at 60° C. under N2 overnight. The mixture was cooled, and then acidified with aqueous HCl (2 M, 12 mL) to pH=3 followed by a standard aqueous/EtOAc workup and purification by prep-HPLC (0.1% TFA as additive) to give Compound 167 (58 mg, 2-step yield 20%) as off-white solid. 1H NMR (CD3OD 400 MHz): δ 7.81 (d, J=8.0 Hz, 1H), 7.38 (s, 1H), 7.25-7.20 (m, 3H), 6.88-6.78 (m, 3H), 6.84 (d, J=8.0 Hz, 1H), 6.82 (s, 1H), 5.17 (s, 1H), 3.77 (s, 3H). MS (ESI): m/z 390.7 [M+1]+.

後処理

  1. temperaturewas refluxed under N2 atmosphere overnight
  2. concentrationThe mixture was concentrated under reduced pressure
  3. temperatureThe mixture was cooled
  4. customEtOAc workup and purification by prep-HPLC (0.1% TFA as additive)

出典と根拠

ORDレコード
ord-0a63dc5225a34d77a2d5789e81d56021
出典データセット
uspto-grants-2014_06
特許番号
US08741915B2

反応ノート

読み込み中…