Diisopropylamine → 4-[4-(5-Bromo-1-oxo-1,2-dihydro-isoquinolin-3-yl)-benzyl]-piperazine-1-carboxylic acid tert-butyl ester

Temperature

-78 °C

To a stirred solution of N,N-diisopropylamine (1.56 mL, 11.10 mmol) in THF (5 mL) under N2 at −78° C. was added n-BuLi (2.5M in hexanes) (4.44 mL, 11.10 mmol) and the reaction stirred at −78° C. for 20 min, after which time a solution of 3-bromo-N,N-diethyl-2-methyl-benzamide (1 g, 3.70 mmol) in THF (5 mL) was added, and the reaction stirred at −78° C. for 30 minutes. A solution of 4-(4-cyano-benzyl)-piperazine-1-carboxylic acid tert-butyl ester (1.15 g, 3.70 mmol) in THF (5 mL) was added and the reaction stirred at −78° C. for 2 h. The reaction was quenched with ice and water, EtOAc added and concentrated in vacuo. The crude material was purified by silica gel column chromatography, eluting with isohexane and increasing the polarity to 100% EtOAc to afford 4-[4-(5-bromo-1-oxo-1,2-dihydro-isoquinolin-3-yl)-benzyl]-piperazine-1-carboxylic acid tert-butyl ester as a cream solid (1.22 g, 66%).

1. stirringthe reaction stirred at −78° C. for 30 minutes
2. stirringthe reaction stirred at −78° C. for 2 h
3. customThe reaction was quenched with ice and water, EtOAc
4. additionadded
5. concentrationconcentrated in vacuo
6. customThe crude material was purified by silica gel column chromatography
7. washeluting with isohexane
8. temperatureincreasing the polarity to 100% EtOAc

ORD record

ord-a8caf5504b0a463abffcb360a16ff69a

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09193689B2