4-Aminophenol → (6S)-4-(4-Chlorophenyl)-N-(4-hydroxyphenyl)-2,3,9-trimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepine-6-acetamide

HRID 727263

反応式

HRID 727263 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[C:15]([CH3:19])=[C:16]([CH3:18])[S:17][C:13]=3[N:12]3[C:20]([CH3:23])=[N:21][N:22]=[C:11]3[C@H:10]([CH2:24][C:25]([OH:27])=O)[N:9]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.[NH2:42][C:43]1[CH:48]=[CH:47][C:46]([OH:49])=[CH:45][CH:44]=1>CN(C)C=O.O1CCCC1>[OH:49][C:46]1[CH:47]=[CH:48][C:43]([NH:42][C:25](=[O:27])[CH2:24][C@@H:10]2[N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[C:14]3[C:15]([CH3:19])=[C:16]([CH3:18])[S:17][C:13]=3[N:12]3[C:20]([CH3:23])=[N:21][N:22]=[C:11]23)=[CH:44][CH:45]=1

参加物

7

反応物 4

HCID 4034-AminophenolHCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 668281072-((9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetraazatricyclo(8.3.0.0,2,6)trideca-2(6),4,7,10,12-pentaen-9-yl)acetic acid

生成物 1

HCID 9936746(6S)-4-(4-Chlorophenyl)-N-(4-hydroxyphenyl)-2,3,9-trimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepine-6-acetamide収率 16.8%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-10 °C

実験手順

(S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f]-[1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid (3.0 g) and triethylamine (1.2 ml) are added to a mixed solvent of dimethylformamide (30 ml) and tetrahydrofuran (15 ml). The mixture is cooled to -10° C., and pivaloyl chloride (1.0 ml) is dropwise added at said temperature. Thirty minutes later, a solution of 4-aminophenol (0.99 g) in dimethylformamide (20 ml) is dropwise added at said temperature, and the mixture is stirred at room temperature for 7.5 hours. After the completion of the reaction, tetrahydrofuran is distilled away, and saturated brine (200 ml) is added. The mixture is extracted with ethyl acetate, and the organic layer is washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (ethyl acetate: methanol=10:1) and crystallized from isopropyl alcohol to give 620 mg of (S)-N-(4-hydroxyphenyl)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide as pale-pink powdery crystals, melting point 215°-220° C.

後処理

  1. distillationis distilled away
  2. additionsaturated brine (200 ml) is added
  3. extractionThe mixture is extracted with ethyl acetate
  4. washthe organic layer is washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified by silica gel column chromatography (ethyl acetate: methanol=10:1)
  8. customcrystallized from isopropyl alcohol

出典と根拠

ORDレコード
ord-b9398d3cff9e4eddbf1901b6c3a6be4d
出典データセット
uspto-grants-1998_01
特許番号
US05712274

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