Piperazine → N-(1-(5-chlorobenzo[d][1,3]dioxol-7-yl)ethyl)-2-(methylsulfonyl)-5-(piperazin-1-yl)benzenamine

A solution of 1-(5-chlorobenzo[d][1,3]dioxol-7-yl)ethanamine (50.0 mg, 0.25 mmol), 2,4-difluoro-1-(methylsulfonyl)benzene (49.0 mg, 0.25 mmol) and diisopropylethylamine (129.0 mg, 4.0 mmol) in N,N-dimethylformamide (1 mL) was stirred at 110° C. for 16 h. The reaction was cooled to room temperature, poured over water and extracted with diethyl ether. The crude extract which contained mainly N-(1-(5-chlorobenzo[d][1,3]dioxol-7-yl)ethyl)-5-fluoro-2-(methylsulfonyl)benzenamine was used for the following reactions without further purification. A solution of N-(1-(5-chlorobenzo[d][1,3]dioxol-7-yl)ethyl)-5-fluoro-2-(methylsulfonyl)benzenamine (93.0 mg, 0.25 mmol), piperazine (432.0 mg, 5.0 mmol) and N,N-diisopropylethylamine (0.44 mL, 2.5 mmol) in acetonitrile (1 mL) was stirred at 80° C. for 16 h. The reaction mixture was cooled down and concentrated under reduced pressure. The residue was taken up in dichloromethane, washed with water, dried and concentrated in vacuo. The crude product was purified by silica chromatography (10% methanol in dichloromethane) to yield 15 mg (14%) of desired product. 1H NMR (400 MHz, CDCl3): δ 7.56 (d, 1H), 6.80 (d, 1H), 6.72 (s, 1H), 6.51 (d, 1H), 6.26 (dd, 1H), 5.99 (dd, 2H), 5.92 (s, 1H), 4.59 (m, 1H), 3.21 (m, 4H), 2.57 (m, 4H), 1.59 (d, 3H); MS (ESI) m/z: 438.3 (M++1).

1. extractionextracted with diethyl ether
2. extractionThe crude extract which
3. customwas used for the following reactions without further purification
4. temperatureThe reaction mixture was cooled down
5. concentrationconcentrated under reduced pressure
6. washwashed with water
7. customdried
8. concentrationconcentrated in vacuo
9. customThe crude product was purified by silica chromatography (10% methanol in dichloromethane)

ORD record

ord-dacf8c20b0964842b8d03a49ee3cb76d

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07968538B2