Dimethylformamide → HCID 89692967, Verbindung

In a 40 ml scintillation vial equipped with a magnetic stir bar and fitted with a nitrogen inlet, the 5-amino-2-chloro-N-(3-dimethylaminomethyl-benzyl)-4-[4-(2,5-dimethyl-phenyl)-piperazin-1-yl]-benzamide 13b (142.50 mg, 0.28 mmol) was taken up in clean, dry N,N-dimethylformamide (3.00 ml, 38.74 mmol) and the mixture was stirred at room temperature under nitrogen until all solids were in solution. To this stirred solution was added the HATU (159.70 mg, 0.42 mmol) followed by the N,N-diisopropylethylamine (0.15 ml, 0.86 mmol) and the mixture was again stirred at room temperature until all solids were in solution. The 2-cyclopropyl-oxazole-4-carboxylic acid 1h (55.70 mg, 0.36 mmol) was added to the mixture and the reaction was allowed to stir over night at room temperature. The reaction was diluted with 15 ml of water and 15 ml of ethyl acetate. The layers were separated and the product was extracted from the aqueous using ethyl acetate (3×20 ml). The organic phases were combined and the solution was washed with brine (1×25 ml) and with saturated aqueous lithium chloride solution (2×25 ml). The solution was then dried over Na2SO4; the solution was decanted and the solvent was removed under reduced pressure. The resultant brown oil was then purified using silica gel column chromatography, eluting a gradient of 100% dichloromethane to 90% dichloromethane/9% MeOH/1% NH4OH. The desired product, 2-cyclopropyl-oxazole-4-carboxylic acid {4-chloro-5-(3-dimethylaminomethyl-benzylcarbamoyl)-2-[4-(2,5-dimethyl-phenyl)-piperazin-1-yl]-phenyl}-amide 13c (33.60 mg, 0.05 mmol), was isolated as a white solid.

1. customIn a 40 ml scintillation vial equipped with a magnetic stir bar
2. customfitted with a nitrogen inlet
3. stirringthe mixture was again stirred at room temperature until all solids
4. stirringto stir over night at room temperature
5. customThe layers were separated
6. extractionthe product was extracted from the
7. washthe solution was washed with brine (1×25 ml) and with saturated aqueous lithium chloride solution (2×25 ml)
8. dry with materialThe solution was then dried over Na2SO4
9. customthe solution was decanted
10. customthe solvent was removed under reduced pressure
11. customThe resultant brown oil was then purified
12. washeluting a gradient of 100% dichloromethane to 90% dichloromethane/9% MeOH/1% NH4OH

ORD-Eintrag

ord-e79030acf778440092c0be14915b63d5

Quelldatensatz

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09409897B2