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

HRID 53221

반응식

HRID 53221 반응식
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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-50 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-18d12d7ae0ef449493ec80a9679d7a04
출처 데이터셋
uspto-grants-1997_04
특허 번호
US05618821

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