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 2178008ノート

反応式

HRID 2178008 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-6cbb30f6f7024776b979471d99d6cbf1
出典データセット
uspto-grants-2015_06
特許番号
US09067893B2

反応ノート

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