3,5-Dichloropyridazine

[1, 1 '-Bis(diphenylphosphino)ferrocene]dichloropalladium(II)dichloromethane (0.27 g, 0.33 mmol), 9, 9-dimethyl-4, 5-bis(diphenylphosphino)xanthene (0.39 g, 0.67 mmol) and Cs2C03( 13 g, 40.3 mmol) in dry toluene (65 mL) were heated at 40 C for 15 min while N2 was bubbling. Then, tert-butyl carbamate (3.1 g, 26.8 mmol) and 3, 5- dichloropyridazine (CAS 1837-55-4, 2.5 g, 13.4 mmol) were added while N2 was bubbling. The mixture was stirred at 80C for 16 h. The mixture was diluted with H20 and extracted with EtOAc. The organic layer was separated, dried (MgS04), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; EtOAc in heptane, from 0/100 to 50/50). The desired fractions were collected and the solvents evaporated in vacuo to yield intermediate 111 (1.4 g, 45%) and intermediate 112 (0.46 g, 15%) as white solids.[01040] Sodium methoxide (5.84 g, 0.108 mol) was added to a stirred solution of To a solution of racemic 1 -( 1H-indazol-6-yl)spiro [2.2lpentane- 1 -carbonitrile (150 mg, 0.717mmol) (Q.3) in anhydrous DMF (4 mL) was added NaH (43.0 mg, 1.08 mmol) at 0C, and thereaction was stirred for 20 mm. Then (1) The compound 1 (18.5 g), the compound 2 (27.7 g), and potassium carbonate (51.3 g) were suspended in 1, 2-dichloroethane (125 mL), and the reaction mixture was stirred for 3 hours at 85C. Then, the compound 2 (4.6 g), and potassium carbonate (17 g) were added to the reaction mixture, followed by stirring for 3 hours at the same temperature. Thereafter, the compound 2 (13.8 g) was added thereto, followed by stirring further for 1 hour. After the reaction mixture was cooled to room temperature, and an insoluble substance was filtered off. The filtrate was concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate: gradient: 80:20-60:40), and then suspended and washed in hexane, taken by filtration, and dried to give the compound 3 (4.2 g) as a colorless solid. MS (APCI): 299/301 [M+H]+(1) To a suspension of sodium hydride (483 mg) in THF (40 mL) was added a solution of benzyl alcohol (1.1 g) in THF (5 mL) at 0C under argon atmosphere, and then the reaction mixture was stirred for 15 minutes at room temperature. Subsequently, a solution of the compound 1 (1.5 g) in THF (20 mL) was added dropwise thereto at room temperature followed by stirring for 2 hours. Water was added to the reaction mixture, and the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resultant residue was purified by silica gel column chromatography (eluent: chloroform-ethyl acetate; gradient: 95:5-85:15) to give the compound 2 (776 mg) as a colorless liquid. MS(APCI): 221/223 [M+H]+A solution of 6-bromo-l, 2, 3, 4-tetrahydroisoquinoline (185 mg, 0.872 mmol) and triethylamine (260 mu, 1.865 mmol) in NMP (3 mL) was slowly added to solid A solution of 6-bromo-l, 2, 3, 4-tetrahydroisoquinoline (185 mg, 0.872 mmol) and triethylamine (260 mu, 1.865 mmol) in NMP (3 mL) was slowly added to solid To a microwave vial containing

Used in the treatment of asthma and allergy. Potential for antinociceptive and antiinflammatory effects

Molecular Weight:148.98
XLogP3:1.4
Hydrogen Bond Acceptor Count:2
Exact Mass:147.9595035
Monoisotopic Mass:147.9595035
Topological Polar Surface Area:25.8
Heavy Atom Count:8
Complexity:78.4
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes