Dimethylformamide → 2,3-dihydro-1H-1-benzazepine-4-carboxamide dihydrochloride

In THF (5 ml) was dissolved 1-cyclopropylmethyl-7-[4-(2-propoxyethoxy)phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (0.25 g). Under ice-cooling, to the solution were added oxalyl chloride (0.11 ml) and DMF (catalytic amount). The mixture was stirred at room temperature for 1 hour, and the solvent was evaporated under reduced pressure. In THF (25 ml) was dissolved the residue, and the solution was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.14 g) and triethylamine (0.41 ml) in THF (5 ml), under ice-cooling. The mixture was stirred at room temperature overnight under nitrogen atmosphere and the solvent was evaporated under reduced pressure. To the residue was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried with anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified with silica gel column chromatography (ethyl acetate/methanol/triethylamine), which was dissolved in ethyl acetate. To the solution was added 4N hydrochloric acid-ethyl acetate, and the solvent was evaporated to give 1-cyclopropylmethyl-7-[4-(2-propoxyethoxy)phenyl]-N-[4-[[N-methyl-N-tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide dihydrochloride (Compound 36) (0.32 g) as pale yellow amorphous.

1. temperatureUnder ice-cooling, to the solution
2. customthe solvent was evaporated under reduced pressure
3. dissolutionIn THF (25 ml) was dissolved the residue
4. additionthe solution was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.14 g) and triethylamine (0.41 ml) in THF (5 ml), under ice-
5. temperaturecooling
6. stirringThe mixture was stirred at room temperature overnight under nitrogen atmosphere
7. customthe solvent was evaporated under reduced pressure
8. additionTo the residue was added water
9. extractionthe mixture was extracted with ethyl acetate
10. washThe organic layer was washed with water and saturated brine
11. dry with materialdried with anhydrous magnesium sulfate
12. customThe solvent was evaporated
13. customthe residue was purified with silica gel column chromatography (ethyl acetate/methanol/triethylamine), which
14. dissolutionwas dissolved in ethyl acetate
15. additionTo the solution was added 4N hydrochloric acid-ethyl acetate
16. customthe solvent was evaporated

ORD record

ord-96e556dc99b24c93853ac57eae6640ed

Source dataset

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06936602B1