Diisopropylethylamine → (R)-tert-Butyl (1-(1-(5-bromopyrimidin-2-yl)-3-(methylthio)-1H-indole-6-carbonyl)pyrrolidin-3-yl)carbamate

HATU (2.41 g, 6.363 mmol), diisopropylethylamine (3.02 ml, 17.355 mmol) and (R)-pyrrolidin-3-yl-carbamic acid tert-butyl ester (1.18 g, 6.363 mmol) were added to an ice cooled suspension of 223a) (2.1 g, 5.787 mmol) in DMF (20 mL). The resulting mixture was stirred at room temperature for 16 h and then diluted with ice cold water (40 mL). The precipitate was filtered off, washed with water and hexane (3 times) and dissolved in dichloromethane. The solution was successively washed with saturated ammonium chloride solution (2×30 mL), saturated sodium hydrogen solution (2×30 mL), and brine (30 mL). The organic layer was dried over sodium sulfate and concentrated. The residue was triturated with ether. White solid. Yield: 3 g (97% of theory)

1. temperaturecooled
2. filtrationThe precipitate was filtered off
3. washwashed with water and hexane (3 times)
4. dissolutiondissolved in dichloromethane
5. washThe solution was successively washed with saturated ammonium chloride solution (2×30 mL), saturated sodium hydrogen solution (2×30 mL), and brine (30 mL)
6. dry with materialThe organic layer was dried over sodium sulfate
7. concentrationconcentrated
8. customThe residue was triturated with ether

ORD record

ord-11be660605f9467296517d4390e77872

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09315490B2