Hydrochloric Acid → HCID 57917286, compound

Temperature

0 °C

3-Quinolin-6-ylmethyl-imidazo[1,2-b]pyridazine-6-carbonitrile (Example 208; 43 mg, 0.15 mmol) in a 1 M aqueous solution of NaOH (1.8 mL, 1.8 mmol) was heated under microwave irradiation at 200° C. for 30 min. The RM was quenched with a 2 M aqueous solution of HCl (0.9 mL, 1.8 mmol) and diluted with MeOH and filtered over Celite. The filtrate is evaporated and dry under vacuo. The residue was suspended in DCM (3 mL) and cooled at 0° C. Were added DMF (0.01 mL) and, slowly, oxalyl chloride (0.055 mL, 0.65 mmol). The RM was allowed to reach rt and stirred at this temperature for 45 min. The RM was dropped in a 2 M solution of ethylamine in MeOH (6 mL). The RM was stirred at rt for 5 min before being evaporated to dryness and the residue quenched with aqueous saturated NaHCO3 and diluted with EtOAc. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with brine and dried over Na2SO4, filtered and evaporated. The residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA) to yield the title compound as light yellow solid (tR 1.96 min (conditions 8), MH+=332).

1. filtrationfiltered over Celite
2. customThe filtrate is evaporated
3. customdry under vacuo
4. additionWere added DMF (0.01 mL)
5. customto reach rt
6. stirringThe RM was stirred at rt for 5 min
7. custombefore being evaporated to dryness
8. customthe residue quenched with aqueous saturated NaHCO3
9. additiondiluted with EtOAc
10. extractionThe aqueous layer was extracted with EtOAc
11. washthe combined organic layers were washed with brine
12. dry with materialdried over Na2SO4
13. filtrationfiltered
14. customevaporated
15. customThe residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)

ORD record

ord-88f46a0a2fbe495ba902909707641450

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08822468B2