Diisopropylethylamine → 1-Ethyl-4-[2-(4-{1-[3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl]piperazin-2-one

温度

110 °C

DIPEA (0.219 mL, 1.23 mmol) was added to 2-(4-{1-[3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl methanesulfonate (200 mg, 0.41 mmol) and 1-ethylpiperazin-2-one (52.6 mg, 0.41 mmol) in DMF (5 mL) at 20° C. under nitrogen. The resulting solution was stirred at 110° C. for 3 hours and the solvent was removed in vacuo to give an orange gum, which was dissolved in DCM (100 mL) and the solution washed with water (100 mL). The organic layer was passed through a phase separating cartridge and then evaporated to dryness to give an orange gum. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% EtOAc in isohexane then 10% methanolic ammonia in EtOAc. Pure fractions were evaporated to dryness to afford a yellow gum, which was triturated with ether to give 1-ethyl-4-[2-(4-{1-[3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl]piperazin-2-one (77 mg, 36.1%) as a white solid.

1. customthe solvent was removed in vacuo
2. customto give an orange gum, which
3. washthe solution washed with water (100 mL)
4. customseparating cartridge
5. customevaporated to dryness
6. customto give an orange gum
7. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 10% EtOAc in isohexane
8. customPure fractions were evaporated to dryness
9. customto afford a yellow gum, which
10. customwas triturated with ether

ORDレコード

ord-3d4108b6b7ad4f3cbcde4f526be02555

出典データセット

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08258140B2