Hydrochloric Acid → N-{[1-[(3,4-Dichlorophenyl)methyl]-6-hydroxy-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine

HRID 2188759ノート

反応式

HRID 2188759 の反応式
[OH:1][C:2]1[NH:7][C:6](=[O:8])[N:5]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:4](=[O:16])[C:3]=1[C:17]([NH:19][CH2:20][C:21]([O:23]CC)=[O:22])=[O:18].[Cl:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][C:34]=1[Cl:35])[CH2:30]Br.C(=O)([O-])[O-].[Na+].[Na+].Cl>CN(C)C=O>[Cl:26][C:27]1[CH:28]=[C:29]([CH2:30][N:7]2[C:2]([OH:1])=[C:3]([C:17]([NH:19][CH2:20][C:21]([OH:23])=[O:22])=[O:18])[C:4](=[O:16])[N:5]([CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:6]2=[O:8])[CH:32]=[CH:33][C:34]=1[Cl:35]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 6397264-(Bromomethyl)-1,2-dichlorobenzeneHCID 178472773HCID 178472773、化合物

生成物 1

HCID 24831504N-{[1-[(3,4-Dichlorophenyl)methyl]-6-hydroxy-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine収率 10.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
100 °C

実験手順

A mixture of ethyl N-{[6-hydroxy-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycinate (example 11a, 357 mg, 1.03 mmoles), 3,4-dichlorobenzyl bromide (193 uL, 1.13 mmoles) and sodium carbonate (330 mg, 3.1 mmoles) in dimethylformamide (6.0 mL) was stirred under argon at 100° C. for 2.5 hours. The mixture was cooled, poured into 1 molar hydrochloric acid and extracted with ethyl acetate (×2). The ester was hydrolysed by stirring in a mixture of ethanol (3 mL) and 1 molar sodium hydroxide solution (3 mL) for 3 hours. The mixture was acidified and extracted with ethyl acetate. Purification by preparative HPLC (acetonitrile-water—0.1% TFA, 20-100%) and crystallization from ethanol-water gave the title compound (50 mg, 10%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.13 (s, 1 H), 10.11 (t, J=5.68 Hz, 1 H), 7.59 (dd, J=5.18, 3.16 Hz, 2 H), 7.24-7.34 (m, 6 H), 5.01 (s, 2 H), 5.02 (s, 2 H), 4.14 (d, J=5.81 Hz, 2 H).

後処理

  1. temperatureThe mixture was cooled
  2. extractionextracted with ethyl acetate (×2)
  3. stirringby stirring in a mixture of ethanol (3 mL) and 1 molar sodium hydroxide solution (3 mL) for 3 hours
  4. extractionextracted with ethyl acetate
  5. customPurification
  6. customby preparative HPLC (acetonitrile-water—0.1% TFA, 20-100%) and crystallization from ethanol-water

出典と根拠

ORDレコード
ord-a2d3c07f79104e8db454bc28e5afde94
出典データセット
uspto-grants-2012_12
特許番号
US08324208B2

反応ノート

読み込み中…