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

HRID 64778Notes

Reaction equation

HRID 64778 reaction equation
[H-].[K+].[CH3:3][N:4]([CH3:12])[CH2:5][CH2:6][CH:7]([OH:11])[CH2:8][NH:9][CH3:10].C(C[CH2:17][C:18]1[CH:19]=[N:20][C:21]2[C:26]([C:27]=1Cl)=[CH:25][CH:24]=[CH:23][CH:22]=2)(O)=O.N.[O:30]1CCCC1>CO.C(OCC)(=O)C.O>[CH3:3][N:4]([CH3:12])[CH2:5][CH2:6][CH:7]1[CH2:8][N:9]([CH3:10])[C:17](=[O:30])[C:18]2[CH:19]=[N:20][C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:26]=3[C:27]=2[O:11]1

Participants

9

Reactant 5

HCID 222AmmoniaHCID 8028TetrahydrofuranHCID 82127Potassium hydrideHCID 212715613-Carboxyethyl-4-chloroquinolineHCID 21285821HCID 21285821, compound

Product 1

HCID 136894382-[2-(Dimethylamino)ethyl]-2,3-dihydro-4-methyl-1,4-oxazepino[6,7-c]quinolin-5(4H)-one

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

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.

Workup

  1. customof 30 min
  2. customto quench
  3. customthe reaction
  4. customthe mixture was partitioned between isopropanol ether and water
  5. extractionThe aqueous layer was extracted again with two 70 ml portions of isopropyl ether
  6. extractionThe aqueous layer was then continuously extracted for 15 hr with chloroform
  7. customThe chloroform layer was collected
  8. filtrationfiltered
  9. concentrationconcentrated by rotary evaporation at 80°
  10. customThe crude material (18 g) was purified by HPLC
  11. customApproximately 4 g (b 15.6%) of product was obtained on evaporation of fractions

Sources & evidence

ORD record
ord-c3f8435b9801428e9a3fcd9f97c3fb1a
Source dataset
uspto-grants-1986_09
Patent number
US04610819

Reaction notes

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