4-Methylmorpholine → HCID 18674162, compound

Temperature

-10 °C

220 mg of cyclohexylacetic acid was dissolved in 10 ml of tetrahydrofuran. While this solution was being cooled at −10° C., 160 mg of N-methylmorpholine and 220 mg of isobutyl chloroformate were added thereto with stirring. The resulting mixture was stirred for 15 minutes. After the addition of 127 mg of 3-amino-5-(4-fluorophenyl)-4-(4-pyridyl)pyrazole, the mixture was stirred for 30 minutes and then stirred at room temperature for 4 days. After the addition of water, the reaction mixture was extracted with ethyl acetate. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. After the resulting residue was dissolved in 10 ml of methanol, 1 ml of 2N sodium hydroxide was added thereto, followed by stirring at room temperature for 90 minutes. Then, the solvent was distilled off under reduced pressure. After the addition of water, this mixture was extracted with ethyl acetate. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. The resulting residue was purified by column chromatography using 30 g of silica gel [with an elution solvent comprising chloroform-methanol (30:1)]. Thus, 55 mg (29% yield) of the title compound was obtained as colorless crystals.

1. stirringThe resulting mixture was stirred for 15 minutes
2. stirringthe mixture was stirred for 30 minutes
3. stirringstirred at room temperature for 4 days
4. extractionthe reaction mixture was extracted with ethyl acetate
5. dry with materialAfter the organic layer was dried over anhydrous magnesium sulfate
6. distillationthe solvent was distilled off under reduced pressure
7. dissolutionAfter the resulting residue was dissolved in 10 ml of methanol
8. addition1 ml of 2N sodium hydroxide was added
9. stirringby stirring at room temperature for 90 minutes
10. distillationThen, the solvent was distilled off under reduced pressure
11. additionAfter the addition of water
12. extractionthis mixture was extracted with ethyl acetate
13. dry with materialAfter the organic layer was dried over anhydrous magnesium sulfate
14. distillationthe solvent was distilled off under reduced pressure
15. customThe resulting residue was purified by column chromatography

ORD record

ord-3f3f80f1c7db4a36a4b84111722c0b3f

Source dataset

uspto-grants-2003_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06511997B1