Water → (1R,2R)-2-((6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol

Temperature

135 °C

A stirred mixture of 6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2-(methylsulfinyl)benzo[d]oxazole (220 mg, 0.67 mmol) from the previous step, (1R,2R)-2-amino-cyclohexanol (152 mg, 1 mmol), and DIEA (259 mg, 2.01 mmol) in DMA (5 mL) was heated at 135° C. for 2 h. The reaction mixture was cooled to rt, poured into water (30 mL), and extracted with ethyl acetate (50 mL×3). The combined organic layers were washed sequentially with water and brine. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified directly by preparative reverse-phase HPLC to afford (1R,2R)-2-((6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol (68 mg, 27%) as a yellow solid. 1H NMR (300 MHz, DMSO-d6): δ 8.67 (s, 1H), 8.41 (m, 1H), 8.06 (m, 1H), 7.79 (m, 1H), 7.39 (s, 1H), 7.13-7.15 (m, 2H), 5.48 (s, 2H), 4.67 (d, J=3.9 Hz, 1H), 3.30-3.35 (m, 2H), 1.86-1.95 (m, 2H), 1.60-1.65 (m, 2H), 1.15-1.35 (m, 4H); LCMS (ESI) m/z 382 (M+H)+.

1. temperatureThe reaction mixture was cooled to rt
2. extractionextracted with ethyl acetate (50 mL×3)
3. washThe combined organic layers were washed sequentially with water and brine
4. customThe organic layer was separated
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified directly by preparative reverse-phase HPLC

ORD record

ord-9ad606c4d0d349b5a0a33c5899232385

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952058B2