Sodium Chloride → (6-Chloro-5-isopropyl-pyridazin-3-yl)-[2,6-dibromo-4-(tetrahydro-pyran-2-yloxymethyl)-phenyl]-acetonitrile

온도

25 °C

A solution of [2,6-dibromo-4-(tetrahydro-pyran-2-yloxymethyl)-phenyl]-acetonitrile (60) (1.52 g, 3.91 mmol) in N,N-dimethylformamide (9 mL) at 25° C. was treated with sodium hydride (192.8 mg, 4.82 mmol, 60% dispersion in mineral oil). The reaction mixture was stirred at 25° C. for 10 min. At this time, the reaction was treated with a solution of 3,6-dichloro-4-isopropyl-pyridazine (7) (810 mg, 4.24 mmol) in N,N-dimethylformamide (2 mL). The reaction was then heated to 90° C. for 1 h. At this time, the reaction was cooled to 25° C., diluted with water (50 mL), a saturated aqueous sodium chloride solution (50 mL) and a saturated aqueous sodium bicarbonate solution (20 mL). This mixture was extracted with ethyl acetate (200 mL). The organics were washed with a saturated aqueous sodium chloride solution (100 mL), dried with magnesium sulfate, filtered, and concentrated under vacuum. Isco chromatography (120 g, Silica, 2:1 hexanes/ethyl acetate) afforded (6-chloro-5-isopropyl-pyridazin-3-yl)-[2,6-dibromo-4-(tetrahydro-pyran-2-yloxymethyl)-phenyl]-acetonitrile (61) (964 mg, 65%) as an orange viscous oil; LRMS for C21H22Br2ClN3O2 (M+H) at m/z=542. Molecular Weight=543.6894; Exact Mass=540.9767

1. temperatureThe reaction was then heated to 90° C. for 1 h
2. temperatureAt this time, the reaction was cooled to 25° C.
3. extractionThis mixture was extracted with ethyl acetate (200 mL)
4. washThe organics were washed with a saturated aqueous sodium chloride solution (100 mL)
5. dry with materialdried with magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated under vacuum

ORD 기록

ord-0bbcc1a1a7ff429bb21755078033c26a

출처 데이터셋

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07807674B2