Ammonium Chloride → 1-[4-(3-{[4-(Trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxamide

To a solution of 1-[4-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylic acid (36 mg, 0.08 mmol) in N,N-dimethylformamide (0.8 mL) was added ammonium chloride (13 mg, 0.24 mmol), diisopropylethylamine (56 L, 0.32 mmol), and (1H-benzotriazol-1-yloxy)(tripyrrolidin-1-yl)phosphonium hexafluorophosphate (83 mg, 0.16 mmol). The mixture was stirred for 60 minutes at room temperature. The mixture was diluted with ethyl acetate (30 mL), and washed with 1:1 saturated sodium bicarbonate:brine (30 mL), and 1:1 water:brine (30 mL). The aqueous fractions were further extracted with ethyl acetate (30 mL). The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by reverse phase HPLC to provide 8 mg (0.018 mmol, 22% yield) of 1-[4-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxamide as a white solid. MS APCI: [M+H]+ m/z 449.1. 1H NMR (400 MHz, DMSO) δ 10.26 (s, 1H), 8.84 (d, J=4.8 Hz, 1H), 8.01 (s, 1H), 7.55-7.51 (m, 2H), 7.35-7.29 (m, 3H), 7.16 (d, J=7.6 Hz, 1H), 6.84 (s, 1H), 3.93 (m, 2H), 3.09 (m, 2H), 2.37 (m, 1H), 1.97-1.70 (m, 2H), 1.62 (m, 2H). rhSyk=++.

1. washwashed with 1:1 saturated sodium bicarbonate
2. extractionThe aqueous fractions were further extracted with ethyl acetate (30 mL)
3. dry with materialThe combined organic extracts were dried over sodium sulfate
4. concentrationconcentrated under reduced pressure
5. customThe resulting residue was purified by reverse phase HPLC

ORD record

ord-c0e86ca9902b47e993baeeb1451495c9

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08735417B2