Hydrochloric Acid → 2-[4-[4-(2-Methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]-1-hydroxy-butyl]-7-azaindole

HRID 53221

反応式

HRID 53221 の反応式
C1(S([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][N:17]=3)[CH:12]=[CH:11]2)(=O)=O)C=CC=CC=1.[Li]CCCC.[CH3:24][N:25]1[N:29]=[N:28][C:27]([C:30]2[CH:41]=[C:40]([CH3:42])[C:33]([O:34][CH2:35][CH2:36][CH2:37][CH:38]=[O:39])=[C:32]([CH3:43])[CH:31]=2)=[N:26]1.Cl>C1COCC1.O>[CH3:24][N:25]1[N:29]=[N:28][C:27]([C:30]2[CH:41]=[C:40]([CH3:42])[C:33]([O:34][CH2:35][CH2:36][CH2:37][CH:38]([C:11]3[NH:10][C:18]4[C:13]([CH:12]=3)=[CH:14][CH:15]=[CH:16][N:17]=4)[OH:39])=[C:32]([CH3:43])[CH:31]=2)=[N:26]1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 8520781-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridineHCID 190820564-[4-(2-Methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]butyraldehydeHCID 178418339Butyllithium

生成物 1

HCID 190820142-[4-[4-(2-Methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]-1-hydroxy-butyl]-7-azaindole収率 25.5%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-50 °C

実験手順

To a cold solution of 1-phenylsulfonyl-7-azaindole (1.29 g, 5 mmol) in 250 ml of THF was added at -30° C. n-BuLi (2.5M in hexane, 4 ml, 10 mmol). The mixture was stirred at -30°-40° C. for 1 h and then cooled to -50° C. To the above mixture was added dropwise at -50° C. a solution of 4-[4-(2-methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]butyraldehyde (1.37 g, 5 mmol) in 25 ml of THF, and the mixture was stirred at -40°-50° C. for 1 h and then allowed to warm to -5° C. for 2 h. Water was added to the mixture, and the resulting reaction mixture was acidified with 1N HCl solution, and then re-basified with an aqueous sodium bicarbonate solution, extracted with methylene chloride, and the organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica column chromatography (20 cm column, ethyl acetate/hexane, 1/5-1/0; then methylene chloride/acetone 2/1-1/1) followed by recrystallization from methylene chloride/methanol to afford 501 mg (25%) of 2-[4-[4-(2-methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]-1-hydroxy-butyl]-7-azaindole, as a white crystalline solid, m.p.166°-169° C.

後処理

  1. stirringthe mixture was stirred at -40°-50° C. for 1 h
  2. temperatureto warm to -5° C. for 2 h
  3. customthe resulting reaction mixture
  4. extractionre-basified with an aqueous sodium bicarbonate solution, extracted with methylene chloride
  5. dry with materialthe organic layer was dried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica column chromatography (20 cm column, ethyl acetate/hexane, 1/5-1/0
  8. customthen methylene chloride/acetone 2/1-1/1) followed by recrystallization from methylene chloride/methanol

出典と根拠

ORDレコード
ord-18d12d7ae0ef449493ec80a9679d7a04
出典データセット
uspto-grants-1997_04
特許番号
US05618821

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