Hydrochloric Acid → 2-(4-Chlorophenyl)thieno[2,3-d]pyridazin-7(6H)-one

Temperature

0 °C

To a solution of 5-(4-chlorophenyl)thiophene-2-carboxylic acid (890 mg, 3.73 mmol) in anhydrous THF (40 ml) under N2 at −78° C. was added a solution of 1.6 M n-butyllithium in hexane (5.83 ml, 9.32 mmol). The reaction was allowed to warmed to 0° C. over 3 hours whereupon the solution was cooled to −78° C. prior to addition of DMF (2.89 ml, 37.3 mmol). After stirring the mixture at −50° C. for 2 hours, the reaction was quenched with aqueous 1 N HCl (20 ml) prior to extraction with EtOAc (40 ml). The EtOAc extracts were dried over Na2SO4 and concentrated to give light brown solid. Following dissolution of the brown solid in MeOH (20 ml), hydrazine (0.351 ml, 11.19 mmol) was added, followed by conc. HCl (1 ml). The mixture was stirred at reflux for 2 days; whereupon after cooling to RT, the mixture was diluted with a solution of saturated NaHCO3 (15 ml). The resulting precipitate was collected by filtration, washed with water and EtOAc to yield after drying 2-(4-chlorophenyl)thieno[3,2-d]pyridazin-7(6H)-one (860 mg, 3.28 mmol, 87% yield) as brown solid. LC MS at t=2.25 min. (m+H=263) PHENOMENEX® S5 C18 4.6×30 mm column/water-MeOH-TFA 90:10:0.1 to 10:90:0.1 gradient over 2 min at 5 mL/min with 1 min hold at the end of the gradient. 1H NMR (400 MHz, DMSO) δ ppm 7.59 (d, J=8.56 Hz, 2H), 7.88 (d, J=8.56 Hz, 2H), 7.99 (s, 1H), 8.40 (s, 1H), 12.99 (s, 1H)

1. temperaturewas cooled to −78° C.
2. customthe reaction was quenched with aqueous 1 N HCl (20 ml)
3. extractionto extraction with EtOAc (40 ml)
4. dry with materialThe EtOAc extracts were dried over Na2SO4
5. concentrationconcentrated
6. customto give light brown solid
7. stirringThe mixture was stirred
8. temperatureat reflux for 2 days
9. temperaturewhereupon after cooling to RT
10. filtrationThe resulting precipitate was collected by filtration
11. washwashed with water and EtOAc
12. customto yield

ORD record

ord-3ea6f42c569a40a9a8b0f796df588d93

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07973159B2