Isoamyl Nitrite → 1'-[2-(trifluoromethyl)benzyl]-1H-spiro[furo[3,2-f]indazole-5,3'-indol]-2'(1'H)-one

HRID 1965812노트

반응식

HRID 1965812 반응식
F[C:2]1[C:7]([C:8]#[N:9])=[CH:6][C:5]2[C:10]3([CH2:31][O:32][C:4]=2[CH:3]=1)[C:18]1[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=1)[N:12]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26]([F:29])([F:28])[F:27])[C:11]3=[O:30].O.NN.[N:36](OCCC(C)C)=O.[PH2](O)=O.C(=O)(O)[O-].[Na+]>COCCOC>[F:27][C:26]([F:29])([F:28])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[CH2:19][N:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]2([C:5]3[CH:6]=[C:7]4[C:2](=[CH:3][C:4]=3[O:32][CH2:31]2)[NH:36][N:9]=[CH:8]4)[C:11]1=[O:30]

참가 물질

7

반응물 5

HCID 8053Isoamyl NitriteHCID 24654Hydrazine hydrate (1:1)HCID 516892Sodium BicarbonateHCID 4124402Phosphinic AcidHCID 593526726-Fluoro-2'-oxo-1'-[2-(trifluoromethyl)benzyl]-1',2'-dihydrospiro[1-benzofuran-3,3-indole]-5-carbonitrile

생성물 1

HCID 461958541'-[2-(trifluoromethyl)benzyl]-1H-spiro[furo[3,2-f]indazole-5,3'-indol]-2'(1'H)-one수율 10%

시약·촉매·용매 1

HCID 80711,2-Dimethoxyethane용매

실험 절차

To a stirred solution of 6-fluoro-2′-oxo-1′-[2-(trifluoromethyl)benzyl]-1′,2′-dihydrospiro[1-benzofuran-3,3′-indole]-5-carbonitrile (0.44 g, 1.0 mmol) in 1,2-dimethoxyethane (20 mL) was added hydrazine monohydrate (1.0 mL, 21 mmol). The reaction mixture was stirred at reflux for 19 h and concentrated in vacuo. The residue was dissolved in ethanol (20 mL) and isoamyl nitrite (1.50 mL, 10.7 mmol), and hypophosphorous acid (2.0 mL, 18 mmol) was added. The reaction mixture was allowed to stir at ambient temperature for 18 h, neutralized with saturated aqueous sodium bicarbonate and extracted with ethyl acetate (3×100 mL). The combined organic extracts was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography and eluted with ethyl acetate/hexanes (1/1) to afford 1′-[2-(trifluoromethyl)benzyl]-1H-spiro[furo[3,2-f]indazole-5,3′-indol]-2′(1′H)-one (0.04 g, 10%): mp 124-126° C. (ethyl acetate/hexanes); 1H NMR (300 MHz, DMSO-d6) δ 12.83 (s, 1H), 7.83-7.0 (m, 2H), 7.67-7.63 (m, 1H), 7.54-7.49 (m, 1H), 7.27-7.18 (m, 4H), 7.08-7.03 (m, 1H), 6.95-6.94 (m, 1H), 6.81-6.77 (m, 1H), 5.07-4.83 (m, 4H); MS (ES−) m/z 436.2 (M−1).

후처리

  1. temperatureat reflux for 19 h
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in ethanol (20 mL)
  4. stirringto stir at ambient temperature for 18 h
  5. extractionextracted with ethyl acetate (3×100 mL)
  6. dry with materialThe combined organic extracts was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. washeluted with ethyl acetate/hexanes (1/1)

출처 및 근거

ORD 기록
ord-a2a655e92003441fadb1d07636123641
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415370B2

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