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

温度

110 °C

DIPEA (15.27 mL, 87.69 mmol) was added to 2-(4-{1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl methanesulfonate (14.19 g, 29.23 mmol) and 1-methylpiperazin-2-one (CAS 59702-07-7, 3.67 g, 32.15 mmol) in DMA (70 mL). The resulting solution was stirred at 110° C. for 1 hour. The reaction mixture was cooled to room temperature, absorbed onto silica, evaporated to dryness and then purified by flash silica chromatography, elution gradient 0 to 3% MeOH in DCM. Pure fractions were evaporated and the resulting gum was scratched with ether until solid. The solid was stirred in ether (100 mL) for 4 hours then collected by filtration and dried to give 1-methyl-4-[2-(4-{1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl]piperazin-2-one (10.08 g, 68.5%) as a solid.

1. temperatureThe reaction mixture was cooled to room temperature
2. customabsorbed onto silica
3. customevaporated to dryness
4. custompurified by flash silica chromatography, elution gradient 0 to 3% MeOH in DCM
5. customPure fractions were evaporated
6. stirringThe solid was stirred in ether (100 mL) for 4 hours
7. filtrationthen collected by filtration
8. customdried

ORDレコード

ord-5e10f74287f442169ef830d8a0eb204f

出典データセット

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08258140B2