Trifluoroacetic acid → 2-((S)-1-aminoethyl)-3-cyclopropyl-5-fluoro-3H-benzoimidazole-4-carboxylic acid methyl ester

To a solution of 2-((S)-1-tert-butoxycarbonylaminoethyl)-3-cyclopropyl-5-fluoro-3H-benzoimidazole-4-carboxylic acid methyl ester (698 mg, 1.85 mmol) in DCM (3 mL) was added TFA (3 mL) and the reaction mixture stirred at RT for 2 h. The crude mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined and concentrated in vacuo to afford 2-((S)-1-aminoethyl)-3-cyclopropyl-5-fluoro-3H-benzoimidazole-4-carboxylic acid methyl ester as a yellow oil. The resulting residue was treated with 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (486 mg, 2.03 mmol) and DIPEA (970 μL, 5.55 mmol) in n-butanol (3 mL). The reaction mixture was heated in a sealed vial for 20 h at 100° C. After cooling to RT, the volatiles were removed under reduced pressure and the resulting residue purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc) to afford the title compound (780 mg, 88% over 2 steps). LCMS (Method C): RT 2.91 min [M+H]+ 480.22.

1. washwas washed with MeOH
2. concentrationconcentrated in vacuo

ORD record

ord-caf66b4c289e4ac893fbc700c4f8325b

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653089B2