5-Bromo-N-methoxy-N-methylpyridine-3-carboxamide → (5-Bromopyridin-3-yl)(7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)methanone

Temperature

0 °C

To a stirred solution of 5-iodo-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidine (Preparation 93, 4.85 g, 16.9 mmol) in THF (90 mL) at 0° C., under nitrogen was added isopropyl magnesium chloride (9.28 mL, 18.6 mmol, 2.0 M in diethyl ether). The mixture was stirred at 0° C. for 1 hour then a solution of 5-bromo-N-methoxy-N-methylnicotinamide (Preparation 227, 4.55 g, 18.6 mmol) in THF (10 mL) was added dropwise at 0° C. The mixture was warmed to room temperature and stirred for 16 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride (200 mL) and extracted with ethyl acetate (3×200 mL). The combined organics were concentrated under reduced pressure and purified by silica gel column chromatography eluting with gradient of EtOAc:DCM 95:5 to 50:50 to afford a light brown oil. The crude material was recrystallised using EtOAc:heptane (15:200 mL) to afford the title compound as a white solid in 33% yield, 2.16 g.

1. temperatureThe mixture was warmed to room temperature
2. stirringstirred for 16 hours
3. customThe reaction mixture was quenched with saturated aqueous ammonium chloride (200 mL)
4. extractionextracted with ethyl acetate (3×200 mL)
5. concentrationThe combined organics were concentrated under reduced pressure
6. custompurified by silica gel column chromatography
7. washeluting with gradient of EtOAc:DCM 95:5 to 50:50
8. customto afford a light brown oil
9. customThe crude material was recrystallised

ORD record

ord-b65a3577869b4c689d125611176ad862

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846698B2