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

HRID 1965812Notes

Reaction equation

HRID 1965812 reaction equation
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]

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-a2a655e92003441fadb1d07636123641
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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