Indazole-3-carboxylic acid → HCID 10565293, compound

HRID 374109Notes

Reaction equation

HRID 374109 reaction equation
[CH3:1][N:2]1[CH2:8][CH:7]([OH:9])[CH2:6][N:5]([CH3:10])[CH2:4][CH2:3]1.C([Li])CCC.[NH:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]([C:25](O)=[O:26])=[N:17]1>O1CCCC1.CCCCCC.CN(C)C=O>[NH:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]([C:25]([O:9][CH:7]2[CH2:6][N:5]([CH3:10])[CH2:4][CH2:3][N:2]([CH3:1])[CH2:8]2)=[O:26])=[N:17]1

Participants

7

Reactant 3

HCID 78250Indazole-3-carboxylic acidHCID 14999065HCID 14999065, compoundHCID 178418339Butyllithium

Product 1

HCID 10565293HCID 10565293, compoundYield 67.5%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1,4-dimethy-6-hydroxyhexahydro-1H-1,4-diazepine (1.9 g) in anhydrous tetrahydrofuran (10 ml), a solution of n-butyllithium in hexane (9.4 g) is added dropwise under nitrogen stream at 25° C., and the mixture is stirred for 30 minutes at the same temperature. To the reaction mixture is added dropwise, the reaction mixture prepared by the following method; to a solution of 1H-indazole-3-carboxylic acid (2.0 g) in anhydrous N,N-dimethylformamide (20 ml), N,N'-carbonyldiimidazole (2.0 g) is added at 25° C., and the mixture is heated at 80° C. for 4.5 hours and cooled to 25° C. The resulting reaction mixture is refluxed with stirring for 1 hour. Tetrahydrofuran is evaporated under reduced pressure, and the residue is diluted with water, extracted with diethyl ether. The organic layer is washed with saturated sodium chloride solution and dried over magnesium sulfate. The solvent is evaporated under reduced pressure, and the residue is chromatographed on silica gel with elution of chloroform-methanol ( 9:1). Fractions containing the title compound are pooled and evaporated under reduced pressure to give the title compound (2.4 g) as an oil. The free base is converted to 5/2 fumarate 1/4 ethanol of the title compound in a usual manner, m.p. 184°-185° C. (recrystallized from ethanol).

Workup

  1. additionTo the reaction mixture is added dropwise
  2. customthe reaction mixture prepared by the following method
  3. temperaturecooled to 25° C
  4. customThe resulting reaction mixture
  5. temperatureis refluxed
  6. stirringwith stirring for 1 hour
  7. customTetrahydrofuran is evaporated under reduced pressure
  8. additionthe residue is diluted with water
  9. extractionextracted with diethyl ether
  10. washThe organic layer is washed with saturated sodium chloride solution
  11. dry with materialdried over magnesium sulfate
  12. customThe solvent is evaporated under reduced pressure
  13. customthe residue is chromatographed on silica gel with elution of chloroform-methanol ( 9:1)
  14. additionFractions containing the title compound
  15. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-57c94f65d432425188aef0b3dcbab69c
Source dataset
uspto-grants-1992_11
Patent number
US05166341

Reaction notes

Loading…