1,2-Dichloroethane → HCID 89690658, compound

In a 25 ml round bottom flask equipped with a magnetic stir bar and fitted with a septum containing a nitrogen inlet, the 2-((E)-2-ethoxy-vinyl)-5-nitro-4-(4-o-tolyl-piperazin-1-yl)-benzoic acid methyl ester 10b (209.90 mg, 0.49 mmol) was taken up in clean, dry 1,2-dichloroethane (3.50 ml, 44.42 mmol) and was stirred at room temperature under nitrogen until all solids were in solution. To this was slowly added the trifluoroacetic acid (0.80 ml, 10.77 mmol) and the reaction was stirred at room temperature for 30 min. After 30 min., the volatiles were removed from the solution under reduced pressure. The resultant red-orange oil was taken up in 5 ml of DCE and the volatiles were removed under reduced pressure once more. The red-orange semi-solid was then taken up in 1,2-dichloroethane (3.50 ml, 44.42 mmol) and stirred vigorously under nitrogen. The 3-dimethylaminomethyl-benzylamine (202.60 mg, 1.23 mmol) was added to the solution followed by the triethylamine (0.17 ml, 1.22 mmol) and the mixture was stirred until a homogeneous solution was achieved. The sodium triacetoxyborohydride (365.90 mg, 1.73 mmol) was added to the reaction mixture and the reaction was warmed to 60° C. and was stirred under nitrogen. The reaction stirred at elevated temperatures overnight. The reaction was cooled to room temperature and the reaction mixture was diluted with 10 ml of dichloromethane and with 10 ml of water. The product was then extracted from the aqueous layer using dichloromethane (3×10 ml) and the organic phases were combined, washed with brine (1×25 ml) and the solution was then dried over MgSO4. The product solution was then filtered under vacuum and the collected solution was further concentrated under reduced pressure. The product was purified using silica gel column chromatography, eluting a gradient of 100% dichloromethane to 10% MeOH in dichloromethane. The product, 2-(3-dimethylaminomethyl-benzyl)-7-nitro-6-(4-o-tolyl-piperazin-1-yl)-3,4-dihydro-2H-isoquinolin-1-one 11a (140.80 mg, 0.27 mmol), was isolated as a yellowish solid and was carried on without further purification. LCMS=513 (M+H).

1. customIn a 25 ml round bottom flask equipped with a magnetic stir bar
2. customfitted with a septum
3. additioncontaining a nitrogen inlet
4. stirringthe reaction was stirred at room temperature for 30 min
5. customthe volatiles were removed from the solution under reduced pressure
6. customthe volatiles were removed under reduced pressure once more
7. stirringstirred vigorously under nitrogen
8. stirringthe mixture was stirred until a homogeneous solution
9. temperaturethe reaction was warmed to 60° C.
10. stirringwas stirred under nitrogen
11. stirringThe reaction stirred at elevated temperatures overnight
12. temperatureThe reaction was cooled to room temperature
13. extractionThe product was then extracted from the aqueous layer
14. washwashed with brine (1×25 ml)
15. dry with materialthe solution was then dried over MgSO4
16. filtrationThe product solution was then filtered under vacuum
17. concentrationthe collected solution was further concentrated under reduced pressure
18. customThe product was purified
19. washeluting a gradient of 100% dichloromethane to 10% MeOH in dichloromethane

ORD record

ord-c442ad184a6e45dd867f0ca82b1f5a21

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09409897B2