Diisopropylethylamine → (R)-tert-Butyl 6-(methyl(1-(pyridin-4-yl)piperidin-4-yl)carbamoyl)-2,3-dihydro-1H-inden-1-ylcarbamate

HATU (0.795 g, 2.09 mmol, 1 eq) and DIPEA (350 μA 2.04 mmol, 2.5 eq) were added to an ice-cooled solution of (R)-3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid (368 mg, 2.09 mmol, 1 eq) in THF (5 ml), and stirring was carried out for 30 min. N-Methyl-1-(pyridin-4-yl)piperidin-4-amine (AMN-06) (400 mg, 2.09 mmol, 1 eq) was dissolved in THF (5 ml) and added dropwise to the reaction solution, and stirring was carried out for 16 h at RT. The reaction solution was diluted with dichloromethane (100 ml), washed with sat. sodium hydrogen carbonate solution (50 ml), sat. ammonium chloride solution (50 ml), water (50 ml) and sat. NaCl solution (50 ml), dried over sodium sulfate and concentrated under reduced pressure. After purification by column chromatography (silica gel, 0.5% MeOH in dichloromethane), the desired product was obtained in the form of a yellowish solid. Yield: 64% (600 mg, 1.33 mmol).

1. additionadded dropwise to the reaction solution
2. stirringstirring
3. waitwas carried out for 16 h at RT
4. washwashed with sat. sodium hydrogen carbonate solution (50 ml), sat. ammonium chloride solution (50 ml), water (50 ml) and sat. NaCl solution (50 ml)
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customAfter purification by column chromatography (silica gel, 0.5% MeOH in dichloromethane)

ORD record

ord-ec2e0bf5e8de43749aca068e08f12ef6

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08680159B2