Реакция #168008

Уравнение реакции

2-chloro-4-methyl-5,6,7,8-tetrahydro-1,6-naphthyridine hydrochloride

methyl 3-cyclopropyl-3-oxopropanoate

4-pyrrolidinopyridine

DIPEA

→

1-(2-chloro-4-methyl-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)-3-cyclopropylpropane-1,3-dione

Выход 52.4%

Растворители

EtOAc

toluene

Условия реакции

Обработка

1. 1
   Другоеto irradiated
2. 2
   ЭкстракцияThe products were extracted twice with EtOAc
3. 3
   ПромывкаThe combined organic layer was washed with a mixed solution of 1M HClaq/brine (1 mL/2 mL)
4. 4
   Сушкаdried over Na2SO4
5. 5
   Фильтрацияfiltered
6. 6
   Концентрированиеconcentrated
7. 7
   Другоеto give crude
8. 8
   ДругоеThe residue was purified by flash column chromatography on 12 g of silica gel (eluent: DCM/EtOAc=90:10 to 0:100)

Методика

Microwave was used to irradiated a suspension of 2-chloro-4-methyl-5,6,7,8-tetrahydro-1,6-naphthyridine hydrochloride (1.00 g, 4.56 mmol), methyl 3-cyclopropyl-3-oxopropanoate (1.298 g, 9.13 mmol), 4-pyrrolidinopyridine (0.068 g, 0.456 mmol) and DIPEA (1.20 mL, 6.85 mmol) in toluene (10 mL) at 150° C. for 45 min. The mixture was cooled to rt and diluted with 1 M HClaq (10 mL) and EtOAc. The products were extracted twice with EtOAc. The combined organic layer was washed with a mixed solution of 1M HClaq/brine (1 mL/2 mL), dried over Na2SO4, filtered, and concentrated to give crude. The residue was purified by flash column chromatography on 12 g of silica gel (eluent: DCM/EtOAc=90:10 to 0:100) to give crude 1-(2-chloro-4-methyl-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)-3-cyclopropylpropane-1,3-dione (0.70 g): MS (ESI+) m/z 293.31 (M+H)+. The obtained material was used without further purification.

Источник