Water → HCID 59352662, compound

HRID 1407935Notes

Reaction equation

HRID 1407935 reaction equation
[CH3:1][C:2]1[C:6]2[CH:7]=[C:8]3[C:13]4([C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[NH:15][C:14]4=[O:22])[CH2:12][O:11][C:9]3=[CH:10][C:5]=2[O:4][N:3]=1.[H-].[Na+].Br[CH2:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[O:37][N:36]=[CH:35][CH:34]=2)=[CH:29][CH:28]=1.O>CN(C)C=O>[CH3:1][C:2]1[C:6]2[CH:7]=[C:8]3[C:13]4([C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[N:15]([CH2:26][C:27]5[CH:28]=[CH:29][C:30]([C:33](=[O:37])[CH2:34][C:35]#[N:36])=[CH:31][CH:32]=5)[C:14]4=[O:22])[CH2:12][O:11][C:9]3=[CH:10][C:5]=2[O:4][N:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 229975455-(4-(Bromomethyl)phenyl)isoxazoleHCID 593524533-methylspiro[furo[3,2-f][1,2]benzisoxazole-5,3'-indol]-2'(1H)-one

Product 1

HCID 59352662HCID 59352662, compoundYield 73.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-methylspiro[furo[3,2-f][1,2]benzisoxazole-5,3′-indol]-2′(1′H)-one (0.35 g, 1.20 mmol) in anhydrous N,N-dimethylformamide (20 mL) at 0° C. was added slowly sodium hydride (60% w/w dispersion in mineral oil, 0.072 g, 1.50 mmol). The solution was stirred at ambient temperature for 30 min, 5-(4-(bromomethyl)phenyl)isoxazole (Sasaki et al., Biorg. Med. Chem. Lett. (1998) 8:2241-2246) (0.24 g, 1.00 mmol) was added and the mixture was stirred for 16 h at ambient temperature. The reaction mixture was poured into water (200 mL) and extracted with ethyl acetate (3×200 mL). The combined organic extracts were washed with brine (3×100 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography and eluted with a 15% to 50% gradient of ethyl acetate in hexanes to afford 3-{4-[(3-methyl-2′-oxospiro[furo[3,2-f][1,2]benzisoxazole-5,3′-indol]1′(2′H)-yl)methyl]phenyl}-3-oxopropanenitrile (0.33 g, 61%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 7.96-7.92 (m, 2H), 7.63-7.60 (m, 2H), 7.50-7.46 (m, 1H), 7.23-7.13 (m, 2H), 7.04, 6.97 (m, 2H), 6.71-6.67 (m, 1H), 5.43-4.76 (m, 4H), 4.06 (s, 2H), 2.46 (s, 3H).

Workup

  1. stirringthe mixture was stirred for 16 h at ambient temperature
  2. extractionextracted with ethyl acetate (3×200 mL)
  3. washThe combined organic extracts were washed with brine (3×100 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography
  8. washeluted with a 15% to 50% gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-88657e1949754bbf9ddf04bfd21414be
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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