4-Methoxybenzylamine → HCID 131734787, compound

Temperature

120 °C

4-Methoxybenzylamine (485 mg, 3.53 mmol) was added to 2-chloro-N-(2-methoxyethyl)-5-(trifluoromethyl)pyridin-4-amine (intermediate 86, 300 mg, 1.18 mmol) and heated in a MW in a septum sealed vial at 60° C. for 3 h. Conventional heating was then continued for 18 h at 80° C., the reaction mixture cooled, additional 4-methoxybenzylamine (162 mg, 1.18 mmol) added and heating continued at 100° C. for 22 h. The reaction mixture was then heated for 9 h at 120° C., cooled, partitioned between saturated aqueous NaHCO3 solution and DCM, extracted 3X with DCM, the organic layers dried over Na2SO4 and evaporated. The residue was applied to a 24 g RediSep® silica column as a DCM solution and purified by normal phase chromatography, eluting with a gradient from DCM to 20% EtOAc in DCM. Product containing fractions were combined and evaporated to give the title compound as a white solid. (UPLC-MS 6) tR 0.77; ESI-MS 356.3 [M+H]+.

1. temperatureheated in a MW in a septum
2. customsealed vial at 60° C. for 3 h
3. temperatureConventional heating
4. temperaturethe reaction mixture cooled
5. temperatureheating
6. waitcontinued at 100° C. for 22 h
7. temperaturecooled
8. custompartitioned between saturated aqueous NaHCO3 solution and DCM
9. extractionextracted 3X with DCM
10. dry with materialthe organic layers dried over Na2SO4
11. customevaporated
12. custompurified by normal phase chromatography
13. washeluting with a gradient from DCM to 20% EtOAc in DCM
14. additionProduct containing fractions
15. customevaporated

ORD record

ord-12bd82318cc54480a60553666b711169

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266883B2