Hydrochloric Acid → 3-(4-Benzyl-2-methylpiperazin-1-yl)-6-(4-fluorophenyl)-4,5-dimethylpyridazine

온도

50 °C

Treat a solution of 1-benzyl-4-(6-(4-fluorophenyl)-4,5-dimethylpyridazin-3-yl)-3-methylpiperazin-2-one (2.84 g, 7.02 mmol) in THF (70 mL) with borane-methyl sulfide complex (1.96 mL, 21.1 mmol). Heat the resulting mixture at 50° C. for 2 h. Cool the reaction mixture in an ice bath, add MeOH (20 mL) via a dropping funnel followed by 4 M HCl in 1,4-dioxane (20 mL). Heat the resulting mixture at 65° C. for 1 h. Concentrate the mixture under reduced pressure. Partition the residue between CH2Cl2 and saturated NaHCO3 (aq). Separate the layers, and extract the aqueous layer with CH2Cl2. Combine the organic layers, dry over Na2SO4, filter, and concentrate under reduced pressure. Purify the residue by flash silica gel chromatography (gradient of 0 to 3% 2 M NH3/MeOH in CH2Cl2) to afford the title compound as a waxy solid (2.45 g, 89%). ES/MS m/z 391.2 (M+1).

1. temperatureCool the reaction mixture in an ice bath
2. temperatureHeat the resulting mixture at 65° C. for 1 h
3. concentrationConcentrate the mixture under reduced pressure
4. customPartition the residue between CH2Cl2 and saturated NaHCO3 (aq)
5. customSeparate the layers
6. extractionextract the aqueous layer with CH2Cl2
7. dry with materialdry over Na2SO4
8. filtrationfilter
9. concentrationconcentrate under reduced pressure
10. customPurify the residue by flash silica gel chromatography (gradient of 0 to 3% 2 M NH3/MeOH in CH2Cl2)

ORD 기록

ord-4a51965c934f4e61a13d58129d79af43

출처 데이터셋

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08445493B2