1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 5-(4-Bromo-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid ((S)-2-hydroxy-propoxy)-amide

To a solution of 5-(4-bromo-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (271 mg, 0.77 mmol) in dioxane (3.9 mL) was added HOBT (306 mg, 2.3 mmol) and EDCI (442 mg, 2.3 mmol). The reaction mixture was stirred at ambient temperature for 30 minutes then (S)-1-aminooxy-propan-2-ol hydrochloride (294 mg, 2.3 mmol) and DIPEA (1.2 mL, 6.9 mmol) were added, the mixture was then stirred for 60 hours at ambient temperature. The reaction mixture was diluted with ethyl acetate then washed with a saturated aqueous solution of sodium bicarbonate followed by water and brine. The organic phase was isolated, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0 to 100%, ethyl acetate in dichloromethane, then gradient 0 to 10%, methanol in dichloromethane) to afford the title compound as a green/yellow solid (80 mg, 25%). LCMS (method A): RT=5.71 min, [M+H]+=423/425. 1H NMR (DMSO-d6): 8.10 (1 H, s), 7.51 (1 H, dd, J=10.87, 2.22 Hz), 7.43 (1 H, s), 7.39 (1 H, d, J=9.31 Hz), 7.18-7.14 (1 H, m), 6.88 (1 H, d, J=9.31 Hz), 6.51 (1 H, t, J=8.85 Hz), 4.69 (1 H, s), 3.68-3.59 (1 H, m), 3.42 (2 H, d, J=5.81 Hz), 0.95 (3 H, d, J=6.35 Hz).

1. stirringthe mixture was then stirred for 60 hours at ambient temperature
2. washthen washed with a saturated aqueous solution of sodium bicarbonate
3. customThe organic phase was isolated
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo

ORD record

ord-26f9cb7b2e3e4a349c17537c5ab10498

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08288408B2