Tetrahydrofuran → HCID 66632564, compound

HRID 2404244Notes

Reaction equation

HRID 2404244 reaction equation
[CH3:1][O:2][C:3]1[C:4]([O:26][CH3:27])=[CH:5][C:6]2[C:7]3[C:15]([C:16]4[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[C:18]([CH:24]=C)[CH:17]=4)=[N:14][NH:13][C:8]=3[CH:9]=[N:10][C:11]=2[CH:12]=1.[O:28]1CCCC1.O=[O+][O-].[BH4-].[Na+]>CN(C)C=O.C(O)C>[CH3:1][O:2][C:3]1[C:4]([O:26][CH3:27])=[CH:5][C:6]2[C:7]3[C:15]([C:16]4[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[C:18]([CH2:24][OH:28])[CH:17]=4)=[N:14][NH:13][C:8]=3[CH:9]=[N:10][C:11]=2[CH:12]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 24823OzoneHCID 4311764Sodium borohydrideHCID 66632518HCID 66632518, compound

Product 1

HCID 66632564HCID 66632564, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
78 °C

Procedure

4-(7,8-Dimethoxy-3H-pyrazolo[3,4-c]quinolin-1-yl)-2-vinylbenzonitrile (247 mg, 693 μmol) is dissolved in N,N-dimethylformamide (1.5 ml), tetrahydrofuran (6.0 ml) and ethanol (9.0 ml) and cooled to (−) 78° C. The reaction solution is subsequently treated with ozone (oxygen flow of ozone generator 50 l/h) for 4 min, nitrogen is then passed through (2 min). After LC-MS check (aldehyde intermediate), NaBH4 (24 mg, 624 μmol) is added, and the reaction mixture is stirred at (−)78° C. for 20 min. The cold bath is subsequently removed, so that the reaction solution warms to room temperature. For purification, the mixture is extracted with ethyl acetate and semi-saturated sodium chloride solution. The organic phase is dried over Na2SO4, filtered with suction and evaporated to dryness at 40° C. in vacuo. The residue is purified by chromatography (pHPLC, solvent gradient water/1-30% by vol. of acetonitrile, 0.1% by vol. of formic acid), and the product fractions are lyophilised, giving 4-(7,8-dimethoxy-3H-pyrazolo[3,4-c]quinolin-1-yl)-2-hydroxymethylbenzonitrile (46 mg, 128 μmol) as a solid. MS: 361.4 (M+H+), TLC (HPTLC): Rf=0.38 (ethyl acetate/ethanol 8:1, parts by volume).

Workup

  1. customis then passed through (2 min)
  2. customThe cold bath is subsequently removed, so that the reaction solution
  3. customwarms to room temperature
  4. customFor purification
  5. extractionthe mixture is extracted with ethyl acetate and semi-saturated sodium chloride solution
  6. dry with materialThe organic phase is dried over Na2SO4
  7. filtrationfiltered with suction
  8. customevaporated to dryness at 40° C. in vacuo
  9. customThe residue is purified by chromatography (pHPLC, solvent gradient water/1-30% by vol. of acetonitrile, 0.1% by vol. of formic acid)

Sources & evidence

ORD record
ord-04336bf57ceb46fb824e7e3dedbd780e
Source dataset
uspto-grants-2014_08
Patent number
US08802712B2

Reaction notes

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