Benzoate → Benzoic Acid

To a solution of methyl 3-(2-((1R,2R)-2((S)-1-(6-trifluoromethyl)pyridin-3yl)piperidin-3-ylamino)cyclohexylamino) oxazol-5-yl)benzoate (69 mg, 0.127 mmol) in THF (0.5 mL) and MeOH (0.5 mL) was added 2M LiOH (1 mL, 2 mmol) in H2O. The reaction mixture was allowed to stir at rt overnight. The reaction mixture was cooled in an ice bath, 1M HCl was added dropwise to pH ˜3. The reaction mixture was concentrated. The resulting residue was purified using RP prep-HPLC method A. The desired fractions were concentrated and then lyophilized with water to give the desired product, 3-(2-((1R,2R)-2((S)-1-(6-trifluoromethyl)pyridin-3yl)piperidin-3-ylamino)cyclohexylamino)oxazol-5-yl)benzoic acid 3TFA salt (86 mg, 0.094 mmol, 74% yield) as a white foam. Anal. Calcd. for C22H30F3N5O3 m/z 529.23, found: 530.2 (M+H)+; 1H NMR (400 MHz, METHANOL-D3) δ ppm 8.26 (d, J=2.7 Hz, 1H), 7.98 (s, 1H), 7.88 (d, J=7.7 Hz, 1H), 7.52 (d, J=8.2 Hz, 1H), 7.47-7.40 (m, 1H), 7.34 (dd, J=8.8, 2.7 Hz, 1H), 7.28-7.21 (m, 2H), 3.85 (dd, J=13.5, 4.7 Hz, 1H), 3.77-3.61 (m, 2H), 3.52 (dt, J=12.4, 4.5 Hz, 1H), 3.46-3.38 (m, 1H), 3.38-3.26 (m, 1H), 3.14-3.01 (m, 1H), 2.19 (d, J=12.6 Hz, 1H), 2.10-2.00 (m, 2H), 2.00-1.82 (m, 4H), 1.62-1.61 (m, 1H), 1.70-1.53 (m, 2H), 1.52-1.39 (m, 2H).

1. temperatureThe reaction mixture was cooled in an ice bath
2. concentrationThe reaction mixture was concentrated
3. customThe resulting residue was purified
4. concentrationThe desired fractions were concentrated

ORD record

ord-67260d0673634759b87f8b0777038a46

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08815909B2