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

반응식

HRID 727263 반응식
[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

참가 물질

7

반응물 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

생성물 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-acetamide수율 16.8%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매2회HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-10 °C

실험 절차

(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.

후처리

  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

출처 및 근거

ORD 기록
ord-b9398d3cff9e4eddbf1901b6c3a6be4d
출처 데이터셋
uspto-grants-1998_01
특허 번호
US05712274

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