Dimethyl Sulfoxide → HCID 86680016, compound

Temperature

70 °C

1,4-Thiazepane hydrochloride (153 mg, 1 mmol) and DIPEA (0.26 mL, 1.5 mmol) were stirred in DMSO (4 mL) for 15 min at room temperature. 5-Chloro-1-methyl-4-nitro-1H-pyrazole (150 mg, 0.95 mmol) and potassium fluoride (170 mg, 3 mmol) were then added and the reaction mixture was heated at 70° C. for 18 h. The mixture was allowed to cool to room temperature and poured into water (4 mL). The aqueous was extracted with EtOAc (3×10 mL) and the combined organic layers were washed with brine (10 mL), separated, dried over MgSO4 and concentrated under reduced pressure to give 3-(1-methyl-4-nitro-1H-pyrazol-5-yl)-8-oxa-3-azabicyclo[3.2.1]octane (220 mg, 92%). This intermediate was dissolved in DCM (10 mL), cooled to 0° C., treated with m-chloroperbenzoic acid (400 mg, 1.9 mmol) and the resulting mixture stirred at room temperature for 16 hr. The resulting precipitate was filtered off washing with cold DCM (5 mL). The filtrate was washed with 2M NaOH (5 mL) and brine (5 mL), passed through a phase separation cartridge and concentrated under reduced pressure to give 4-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,4-thiazepane 1,1-dioxide (280 mg, 97% over two steps) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.14 (s, 1H), 3.87 (s, 3H), 3.59-3.55 (m, 2H), 3.41-3.36 (m, 6H), 2.29-2.24 (m, 2H).

1. temperatureto cool to room temperature
2. extractionThe aqueous was extracted with EtOAc (3×10 mL)
3. washthe combined organic layers were washed with brine (10 mL)
4. customseparated
5. dry with materialdried over MgSO4
6. concentrationconcentrated under reduced pressure

ORD record

ord-442ef23f4fc14b52ba685d33ebd86799

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08614206B2