1,2-Dichloroethane → HCID 89692878, compound

In a 40 ml scintillation vial equipped with a magnetic stir bar, the 2-((E)-2-ethoxy-vinyl)-5-nitro-4-(4-o-tolyl-piperazin-1-yl)-benzoic acid methyl ester 10b (97.10 mg, 0.23 mmol) was taken up in clean, dry 1,2-dichloroethane (2.00 ml, 25.38 mmol) and the mixture was stirred together at room temperature under a nitrogen atmosphere until all solids were in solution. The solution was then cooled to 0° C. using a wet ice bath and the trifluoroacetic acid (0.10 ml, 1.35 mmol) was added slowly. The reaction was allowed to warm to room temperature over an hour. The volatiles were then removed from the reaction mixture under reduced pressure. The resultant deep amber oil was taken up in 2 ml of dichloroethane and once again the volatiles were removed under reduced pressure. The resultant dark-colored semi-solid was then taken back up in 1,2-dichloroethane (2.00 ml, 25.38 mmol) and to this was added the 1-(3-amino-propyl)-pyrrolidin-2-one 1e (0.08 ml, 0.57 mmol) followed by the triethylamine (0.08 ml, 0.57 mmol) and the reaction mixture was stirred for 5 min at room temperature under an inert nitrogen atmosphere. The sodium triacetoxyborohydride (165.50 mg, 0.78 mmol) was added in one portion and the mixture stirred until all solids were in solution. The reaction mixture was then warmed to 60° C. and allowed to stir overnight under an inert nitrogen atmosphere. The reaction was cooled to room temperature and diluted with 10 ml of water along with 10 ml of dichloromethane. The layers were separated and the product was extracted from the aqueous layer using dichloromethane (3×10 ml). The organic phases were combined, washed with brine (1×25 ml) and dried over MgSO4. The product solution was filtered under vacuum and the product solution was then concentrated under reduced pressure. The resultant amber oil was then purified using silica gel column chromatography, eluting a gradient of 100% dichloromethane to 5% MeOH in dichloromethane. 7-nitro-2-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-6-(4-o-tolyl-piperazin-1-yl)-3,4-dihydro-2H-isoquinolin-1-one 10c (71.80 mg, 0.15 mmol) was isolated as an off-white solid and was carried on without further purification. LCMS (m/e)=492 (M+H).

1. customIn a 40 ml scintillation vial equipped with a magnetic stir bar
2. temperatureThe solution was then cooled to 0° C.
3. temperatureto warm to room temperature over an hour
4. customThe volatiles were then removed from the reaction mixture under reduced pressure
5. customonce again the volatiles were removed under reduced pressure
6. stirringthe reaction mixture was stirred for 5 min at room temperature under an inert nitrogen atmosphere
7. stirringthe mixture stirred until all solids
8. temperatureThe reaction mixture was then warmed to 60° C.
9. stirringto stir overnight under an inert nitrogen atmosphere
10. temperatureThe reaction was cooled to room temperature
11. customThe layers were separated
12. extractionthe product was extracted from the aqueous layer
13. washwashed with brine (1×25 ml)
14. dry with materialdried over MgSO4
15. filtrationThe product solution was filtered under vacuum
16. concentrationthe product solution was then concentrated under reduced pressure
17. customThe resultant amber oil was then purified
18. washeluting a gradient of 100% dichloromethane to 5% MeOH in dichloromethane

ORD record

ord-8ba907afb8634ccd847a88609612e5ac

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09409897B2