Dimethylamine → HCID 178463573, compound

A mixture of 5-fluoro-3-phenyl-2-{(S)-1-[9-(tetrahydropyran-2-yl)-9H-purin-6-ylamino]ethyl}-3H-benzoimidazole-4-carboxylic acid (100 mg, 0.2 mmol), HATU (91 mg, 0.24 mmol), dimethylamine (2M in THF, 0.2 mL, 0.4 mmol) and DIPEA (69 μL, 0.4 mmol) in DCM (2 mL) was stirred at RT for 1 h. The crude mixture was diluted with water and extracted with DCM. The aqueous phase was further extracted with DCM and the combined organic fractions were dried (MgSO4) and concentrated in vacuo. The resulting residue was dissolved in MeOH (2 mL) and 4N HCl in dioxane (0.25 mL) and the mixture was stirred at RT for 30 min. The volatiles were removed under reduced pressure and the resulting residue purified by HPLC (Waters C18 XBridge, on a 20 min gradient 10-90%, 0.1% NH4OH in acetonitrile/water) to afford 204 (60 mg, 68%). LCMS (Method K): RT 2.58 and 2.71 min [M+H]+ 445.1. 1H NMR (DMSO-d6, 400 MHz, 80° C.): δ 12.45 (1H, s), 8.04 (1H, d, J=4.86), 8.00 (1H, s), 7.69 (1H, dd, J=8.83, 4.88 Hz), 7.52-7.25 (6H, m), 7.12-7.05 (1H, m), 5.58-5.39 (1H, m), 2.64 (1.5H, s), 2.58 (1.5H, s), 2.34 (3H, d, J=4.31 Hz), 1.56 (3H, t, J=6.63 Hz)

1. extractionextracted with DCM
2. extractionThe aqueous phase was further extracted with DCM
3. dry with materialthe combined organic fractions were dried (MgSO4)
4. concentrationconcentrated in vacuo
5. dissolutionThe resulting residue was dissolved in MeOH (2 mL)
6. stirring4N HCl in dioxane (0.25 mL) and the mixture was stirred at RT for 30 min
7. customThe volatiles were removed under reduced pressure
8. customthe resulting residue purified by HPLC (Waters C18 XBridge

ORD record

ord-b4c7dcc944ed497193d45c0bbb11948c

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653089B2