2,1,3-Benzoxadiazole-4-carbaldehyde → HCID 178509375, compound

HRID 489448Notes

Reaction equation

HRID 489448 reaction equation
[N:1]1[O:2][N:3]=[C:4]2[C:9]([CH:10]=O)=[CH:8][CH:7]=[CH:6][C:5]=12.[NH2:12][C:13]1[CH:17]=[CH:16][NH:15][N:14]=1.[C:18]([CH2:20][C:21]([CH:23]1[CH2:32][CH2:31][CH2:30][CH2:29][C:24]21[O:28][CH2:27][CH2:26][O:25]2)=O)#[N:19]>C(#N)C>[N:1]1[O:2][N:3]=[C:4]2[C:9]([CH:10]3[C:20]([C:18]#[N:19])=[C:21]([CH:23]4[CH2:32][CH2:31][CH2:30][CH2:29][C:24]54[O:28][CH2:27][CH2:26][O:25]5)[NH:12][C:13]4=[N:14][NH:15][CH:16]=[C:17]34)=[CH:8][CH:7]=[CH:6][C:5]=12

Participants

5

Reactant 3

HCID 102908732,1,3-Benzoxadiazole-4-carbaldehydeHCID 22265391HCID 22265391, compoundHCID 178418806HCID 178418806, compound

Product 1

HCID 178509375HCID 178509375, compoundYield 59.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of ethyl 2-cyclohexanonecarboxylate (25 g) in toluene (200 mL) was added ethyleneglycol (10.1 g) and p-toluenesulfonic acid (2.8 g) at room temperature and the mixture was heated under reflux with Dean-Stark apparatus for five hours. The reaction mixture was cooled to room temperature, the solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate (10:1)) to give ethyl 1,4-dioxa-spiro[4,5]decane-6-carboxylate (31 g) as a colorless oil. To a solution of acetonitrile (7.2 g) in THF (700 mL) was added n-BuLi (160 mmol) at −78° C. Further, ethyl 1,4-dioxa-spiro[4,5]decane-6-carboxylate (31 g) was added and the mixture was stirred for an hour. After acidification with hydrochloric acid, the mixture was extracted with ethyl acetate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate (10:1)) to give 1-cyano-2-(1,4-dioxa-spiro[4,5]decan-6-yl)ethan-2-one (14.5 g) as a colorless oil. A solution of 2,1,3-benzoxadiazole-4-aldehyde (0.8 g), 3-aminopyrazole (0.5 g) and 1-cyano-2-(1,4-dioxa-spiro[4,5]-decan-6-yl)ethan-2-one (1.2 g) in acetonitrile (10 mL) was heated under reflux overnight. The reaction mixture was cooled to room temperature, and the precipitated crystals were collected by filtration to give 4-(2,1,3-benzoxadiazol-4-yl)-5-cyano-4,7-dihydro-6-(1,4-dioxa-spiro[4,5]decan-6-yl)-2H-pyrazolo[3,4-b]pyridine (1.3 g) as colorless crystals.

Workup

  1. temperatureunder reflux overnight
  2. filtrationthe precipitated crystals were collected by filtration

Sources & evidence

ORD record
ord-a6ebd8af02dd4ccba040f6c1e8a9f415
Source dataset
uspto-grants-2005_12
Patent number
US06977262B2

Reaction notes

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