4-Methylmorpholine → HCID 2759570, compound

Temperature

45 °C

To a solution of N-[3(R)-1-{3-(1-tert-butoxycarbonyl-4-piperidyl)propionyl}-3-piperidylcarbonyl]-2(S)-amino-β-alanine (250 mg, 0.55 mmol) in acetonitrile (8 mL) was added monosilylacetamide (1.0 g), then the mixture was stirred for 20 minutes at 45° C. After the mixture was allowed to cool to 0° C., N-methylmorpholine (73 mL, 0.66 mmol) and a solution of 4-methoxycyclohexanecarbonyl chloride (0.66 mmol) in dichloromethane (2 mL), which was prepared from 4-methoxycyclohexanecarboxylic acid, oxalyl chloride and N,N-dimethylformamide, were added successively via syringe. After stirring at ambient temperature for 4 hours, the mixture was extracted with ethyl acetate and dried over sodium sulfate. After evaporation of the solvent, the residue was treated with 4N hydrochloric acid in ethyl acetate. The insoluble material was collected by filtration, dried and dissolved in water. The solution was neutralized with a saturated aqueous NaHCO3 solution, purified by an ODS column chromatography using Daisogel-120SP (10% CH3CN/water) and freeze-dried to give N-[3(R)-1-{3-(4-piperidyl)propionyl}-3-piperidylcarbonyl]-2(S)-(4-methoxycyclohexanecarbonyl)amino-β-alanine (244.4 mg, 89.8%) as a white powder.

1. temperatureto cool to 0° C.
2. additionwere added successively via syringe
3. stirringAfter stirring at ambient temperature for 4 hours
4. extractionthe mixture was extracted with ethyl acetate
5. dry with materialdried over sodium sulfate
6. customAfter evaporation of the solvent
7. additionthe residue was treated with 4N hydrochloric acid in ethyl acetate
8. filtrationThe insoluble material was collected by filtration
9. customdried
10. dissolutiondissolved in water
11. custompurified by an ODS column chromatography
12. customfreeze-dried

ORD record

ord-74a80134933e44ea8671cb1c7e521503

Source dataset

uspto-grants-2004_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06812235B2