Hydrochloric Acid → HCID 68535377, compound

Magnesium metal powder (0.27 g, 11.1 mmol) was mixed with iodine (5 mg), heated with a dryer under a nitrogen atmosphere and cooled to room temperature, and anhydrous tetrahydrofuran (15.0 mL) was added thereto. Cyclopropyl bromide (1.33 g, 1.10 mmol), while being kept at 28 to 33° C., was added dropwise to the mixture under stirring at room temperature, and then the mixture was stirred at room temperature for 30 minutes to prepare a pale yellowish gray solution of cyclopropylmagnesium bromide in tetrahydrofuran. Separately, zinc chloride (1.50 g, 11.0 mmol) dried at 180° C. for 4 hours under vacuum was dissolved in anhydrous tetrahydrofuran (10.0 mL) under a nitrogen atmosphere and then kept at 0° C. or less in an ice-sodium chloride bath, during which the previously prepared solution of cyclopropylmagnesium bromide in tetrahydrofuran was added dropwise thereto. The mixture was stirred at about −10° C. for 15 minutes, and [1,3-bis(diphenylphosphino)propane]nickel (II) dichloride (0.27 g, 0.50 mmol) was added as powder to the resulting suspension, and then a solution of N′-(2,6-dichloroimidazo[1,2-b]pyridazin-3-ylsulfonyl)-N,N-diisobutylformamidine (2.03 g, 5.00 mmol) dissolved in anhydrous tetrahydrofuran (10.0 mL) was added dropwise thereto. The mixture was stirred at −10° C. for 2 hours, then at room temperature for 16 hours, poured into an aqueous saturated saline solution, adjusted to pH 2 with dilute hydrochloric acid and extracted 4 times with chloroform. The extracts were combined, dehydrated over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residues were purified by silica gel column chromatography (ethyl acetate:hexane=1:1), whereby 0.64 g (31.5%) of the starting material N′-(2,6-dichloroimidazo[1,2-b]pyridazin-3-ylsulfonyl)-N,N-diisobutylformamidine was recovered and simultaneously the title compound was obtained as pale yellow crystals. The yield was 0.94 g (45.7%).

1. temperatureheated with a dryer under a nitrogen atmosphere
2. customwhile being kept at 28 to 33° C.
3. additionwas added dropwise to the mixture
4. stirringthe mixture was stirred at room temperature for 30 minutes
5. customkept at 0° C. or less in an ice-sodium chloride bath, during which
6. stirringThe mixture was stirred at about −10° C. for 15 minutes
7. additionwas added dropwise
8. stirringThe mixture was stirred at −10° C. for 2 hours
9. additionpoured into an aqueous saturated saline solution
10. extractionextracted 4 times with chloroform
11. concentrationconcentrated under reduced pressure
12. customthe residues were purified by silica gel column chromatography (ethyl acetate:hexane=1:1), whereby 0.64 g (31.5%) of the starting material N′-(2,6-dichloroimidazo[1,2-b]pyridazin-3-ylsulfonyl)-N,N-diisobutylformamidine
13. customwas recovered

ORD record

ord-dfe59332113c4ba69fd045cce13911bd

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399381B2