Reacción #93056

Ecuación de reacción

3-carboxyethyl-4-chloroquinoline

ammonia

4-dimethylamino-1-methylamino-2-butanol

potassium hydride

tetrahydrofuran

→

final product

2-[2-(Dimethylamino)ethyl]-2,3-dihydro-4-methyl-1,4-oxazepino[6,7-c]quinolin-5(4H)-one

Disolventes

methanol

ethyl acetate

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroof 30 min
2. 2
   Otroto quench
3. 3
   Otrothe reaction
4. 4
   Otrothe mixture was partitioned between isopropanol ether and water
5. 5
   ExtracciónThe aqueous layer was extracted again with two 70 ml portions of isopropyl ether
6. 6
   ExtracciónThe aqueous layer was then continuously extracted for 15 hr with chloroform
7. 7
   OtroThe chloroform layer was collected
8. 8
   Filtraciónfiltered
9. 9
   Concentraciónconcentrated by rotary evaporation at 80°
10. 10
    OtroThe crude material (18 g) was purified by HPLC
11. 11
    OtroApproximately 4 g (b 15.6%) of product was obtained on evaporation of fractions

Procedimiento

To a suspension of 19.4 g (35% in oil, 0.172 mole) of potassium hydride in 150 ml of tetrahydrofuran was added at a rapid drop, 12.4 g (0.086 mole) of 4-dimethylamino-1-methylamino-2-butanol. After 10 min., 20 g (0.086 mole) of 3-carboxyethyl-4-chloroquinoline was added via a powder dropping funnel over a period of 30 min. The mixture was stirred at room temperature overnight. Approximately 50 ml of water was added to quench the reaction and the mixture was partitioned between isopropanol ether and water. The aqueous layer was extracted again with two 70 ml portions of isopropyl ether. The aqueous layer was then continuously extracted for 15 hr with chloroform. The chloroform layer was collected, filtered and concentrated by rotary evaporation at 80°, 30 mm. The crude material (18 g) was purified by HPLC using silica gel as the stationary phase and 3% triethylamine/ethanol as the eluent. Approximately 4 g (b 15.6%) of product was obtained on evaporation of fractions having a similar thin layer chromatograph (TLC) using ethyl acetate, methanol and aqueous conc. ammonia (7:2:1 parts by volume respectively) on silica. TLC of the final product using the same solvent mix on silica was identical to that of the free base of the same compound prepared in Example 2. C.I. mass spec showed M+H of 300. The oxalate salt was also identical to that obtained in Example 2.

Fuente