1143532-39-1

1143534-59-1

3680-69-1

1143532-39-1

General steps: 1. N,N-diisopropylethylamine (1.676 mL, 9.62 mmol) was added under nitrogen protection to a solution containing (S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)piperidine-4-carboxamide (Intermediate 49) (1 g, 3.21 mmol) and 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (0.493 g 3.21 mmol) in a solution of n-butanol (15 mL). 2. The reaction mixture was stirred at 60 °C for 18 hours. 3. After completion of the reaction, the reaction mixture was diluted with ethyl acetate (50 mL) and washed sequentially with water (25 mL) and saturated saline (25 mL). 4. The organic layer was separated, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain the crude product. 5. The crude product was purified by fast silica gel column chromatography using dichloromethane with a gradient elution containing 0 to 6% methanol and ammonia. 6. The purified fraction was collected and concentrated to dryness under reduced pressure to afford (S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (842 mg) as a white foamy solid. 7. The resulting product was dissolved in ethyl acetate (7 mL) and stirred for 18 hours. 8. The precipitated solid was collected by filtration, washed with a small amount of ethyl acetate and dried in a vacuum oven at 55 °C for 18 h. (S)-4-Amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (0.585 g, 42.5% yield) was obtained as a white solid. Mass spectrum (electrospray positive ion mode): m/z (ES+) (M + H)+ = 429; HPLC retention time tR = 1.60 min. 1H NMR (400.13 MHz, DMSO-d6) δ 1.39-1.47 (2H, m), 1.80-2.02 (4H, m), 2.17 (2H, s), 3.35-3.40 (2H, m), 3.50-3.59 (2H, m), 4.34-4.41 (2H, m), 4.53 (1H, t), 4.88 (1H, d), 6.57 (1H, m), 7.14-7.16 (1H, m), 7.31-7.37 (4H, m), 8.12 (1H, s), 8.42 (1H, d), 11.62 (1H, s).