Toluene → HCID 21955784, compound

Temperature

55 °C

A 12 g (0.3 mole) sample of 60% sodium hydride was added to dimethylformamide (DMF) with stirring and cooling. 11H-Pyrido[2,3-b][1,4]benzodiazepin-6(5H)-one, 21.1 g (0.10 mole) as a powder, was added and rinsed in with dimethylformamide (DMF). The total DMF used was 100 ml. The reaction mixture was warmed to 55° C. for 10 min, then cooled down to 35° C. and the 3-dimethylaminopropyl chloride solution, as prepared above, was added. The reaction mixture was slowly heated to 65° C. over a one hour period, after which it was allowed to cool to room temperature overnight. The reaction mixture was treated with saturated ammonium chloride solution and diluted with toluene. Precipitate, 2.6 g, was filtered off and identified as starting 11H-pyrido[2,3-b][1,4]benzodiazepin-6(5H)-one. The filtrate separated into two layers, an aqueous layer and a toluene layer. The aqueous layer was extracted four times with toluene. All toluene layers were back washed with water, dried over sodium sulfate and concentrated to give a dark brown oil. The oil was suspended in a mixture of isopropanol and isopropyl ether. The mixture was filtered to remove a small amount of starting 11H-pyrido[2,3-b][1,4]benzodiazepin-6(5H)-one. The filtrate was acidified with a solution of hydrogen chloride in isopropanol. The solid was collected by filtration and rinsed with isopropyl ether and dried to give 27.6 g of product in 83% yield, m.p. 174°-178° C. Mass spectroscopy showed (M+1)+ : m/e 297. Proton NMR analysis of a sample dissolved in D2O and basified with KOD and extracted with DCCL3 (ppm) was found to be as follows: 8.20 to 6.80 (multiplet, 7H, aromatic): 3.95 (triplet, 2H, methylene protons of the propylene chain next to the ring nitrogen): 2.20 (singlet, 6H, methyl protons of the dimethylamino group); 2.55 to 1.55 (multiplet, 4H, methylene protons of the remainder of the propylene chain); 1.20 (multiplet, methyl protons of the residual 2-propanol and isopropyl ether).

1. temperaturecooling
2. washrinsed in with dimethylformamide (DMF)
3. temperaturecooled down to 35° C.
4. customthe 3-dimethylaminopropyl chloride solution, as prepared above,
5. additionwas added
6. temperatureThe reaction mixture was slowly heated to 65° C. over a one hour period
7. temperatureto cool to room temperature overnight
8. filtrationPrecipitate, 2.6 g, was filtered off
9. customThe filtrate separated into two layers
10. extractionThe aqueous layer was extracted four times with toluene
11. washAll toluene layers were back washed with water
12. dry with materialdried over sodium sulfate
13. concentrationconcentrated
14. customto give a dark brown oil
15. filtrationThe mixture was filtered
16. customto remove a small amount of starting 11H-pyrido[2,3-b][1,4]benzodiazepin-6(5H)-one
17. filtrationThe solid was collected by filtration
18. washrinsed with isopropyl ether
19. customdried

ORD record

ord-d173b41968fe45b996de2efd5a541d26

Source dataset

uspto-grants-1988_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04749788