1-Methylpiperazine → 3-Methyl-4-(4-methyl-piperazin-1-yl)isoxazolo[5,4-b]pyridine-5-carboxylic acid

HRID 1611929Notes

Reaction equation

HRID 1611929 reaction equation
Cl[C:2]1[C:7]([C:8]([O:10]CC)=[O:9])=[CH:6][N:5]=[C:4]2[O:13][N:14]=[C:15]([CH3:16])[C:3]=12.[CH3:17][N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1>O1CCCC1>[CH3:16][C:15]1[C:3]2[C:4](=[N:5][CH:6]=[C:7]([C:8]([OH:10])=[O:9])[C:2]=2[N:21]2[CH2:22][CH2:23][N:18]([CH3:17])[CH2:19][CH2:20]2)[O:13][N:14]=1

Participants

4

Reactant 2

HCID 531671-MethylpiperazineHCID 10847662Ethyl 4-chloro-3-methylisoxazolo[5,4-b]pyridine-5-carboxylate

Product 1

HCID 222524003-Methyl-4-(4-methyl-piperazin-1-yl)isoxazolo[5,4-b]pyridine-5-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A solution of ethyl 4-chloro-3-methylisoxazolo[5,4-b]pyridin-5-carboxylate (1.02 g) and 1-methylpiperazine (1.12 ml) in tetrahydrofuran (10 ml) was stirred at room temperature for 1 hr and then concentrated under reduced pressure. The residue was treated with water, the precipitated solid was filtered, washed with water, and dried under high vacuum. This solid was suspended in ethanol (1 ml), added 5N NaOH (11 ml , and the mixture was stirred at 60° C. for 1 hr. The reaction mixture was treated with 5N HCl and purified by ODS column (VARIAN MEGABOND ELUT C18) to give 3-methyl-4-(4-methyl-piperazin-1-yl)isoxazolo[5,4-b]pyridine-5-carboxylic acid as an amorphous solid. A portion of this amorphous solid (417 mg) was dissolved in thionyl chloride (40 ml) and heated at 50° C. for 3.5 hrs. The mixture was concentrated under reduced pressure, the residue was dissolved in THF (20 ml), and reacted with ammonia gas at room temperature for 3 hrs. The reaction mixture was concentrated under reduced pressure, the residue was treated with water, the resulting solid was filtered, washed with water, and dried under high vacuum to give the 3-methyl-4-(4-methylpiperazin-1-yl)-isoxazolo[5,4-b]pyridin-5-carboxylic acid amide.

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe residue was treated with water
  3. filtrationthe precipitated solid was filtered
  4. washwashed with water
  5. customdried under high vacuum
  6. additionadded 5N NaOH (11 ml
  7. additionThe reaction mixture was treated with 5N HCl
  8. custompurified by ODS column (VARIAN MEGABOND ELUT C18)

Sources & evidence

ORD record
ord-3bfe812328c34f65b31d545cd833fe5f
Source dataset
uspto-grants-2006_01
Patent number
US06992086B2

Reaction notes

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