3-Methyl-5-isoxazolecarboxylic acid → (R)-Methyl 3-(5-methyl isoxazole-3-carboxamido)-2,3-dihydro-1H-indene-5-carboxylate

HATU (4.4 g, 11.7 mmol, 1.5 eq) and DIPEA (3.0 ml, 15.6 mmol, 2 eq) were added to an ice-cooled solution of 5-methylisoxazole-3-carboxylic acid (990 mg, 7.8 mmol, 1 eq) in dichloromethane (80 ml), and stirring was carried out for 30 min. (R)-Methyl 3-amino-2,3-dihydro-1H-indene-5-carboxylate (A-07) (7.8 mmol, 1 eq) was dissolved in dichloromethane (20 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 (250 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, 2% MeOH in dichloro-methane), the desired product was obtained in the form of a yellowish solid. Yield: 68% (1.6 g, 5.3 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, 2% MeOH in dichloro-methane)

ORD record

ord-ac9b345feb254794b0b10f4174186e12

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08680159B2