Reaction Steps
To a solution of 1-(4-(3-cyclopropyl-1H-pyrazol-5-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-hydroxypyrrolidine-2-carboxylic acid (200 mg, 0.54 mmol) in DMF (3 mL) was added 6-fluoropyridin-3-amine (121 mg, 1.08 mmol), HATU (246 mg, 0.648 mmol) and DIPEA (0.16 mL, 0.864 mmol). The reaction mixture was allowed to stir at RT for 16 h. The reaction mixture was diluted with EtOAc (50 mL), washed with water (4×25 mL) and dried over anhydrous sodium sulfate. Removal of EtOAc under reduced pressure gave a crude product that was purified by reverse phase HPLC to afford (2S,4R)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-4-hydroxypyrrolidine-2-carboxamide (10 mg). Compound No. 10a: 1H NMR (400 MHz, CD3OD, freebase) δ (ppm): 0.60-0.68 (m, 2H), 0.80-0.92 (m, 2H), 1.71-1.81 (m, 1H), 1.90-2.01 (m, 1H), 2.03-2.17 (m, 2H), 2.30-2.41 (m, 2H), 2.65-2.83 (m, 4H), 3.75-3.91 (m, 2H), 4.51-4.60 (m, 1H), 6.07 (s, 1H), 6.97 (d, 1H), 7.99 (s, 1H), 8.19 (s, 1H). Compound No. 10b: 1H NMR (400 MHz, CD3OD, freebase) δ (ppm): 0.60-0.68 (m, 2H), 0.80-0.92 (m, 2H), 1.71-1.81 (m, 1H), 1.90-2.01 (m, 1H), 2.03-2.17 (m, 2H), 2.30-2.41 (m, 2H), 2.65-2.83 (m, 4H), 3.75-3.91 (m, 2H), 4.51-4.60 (m, 1H), 6.07 (s, 1H), 6.97 (d, 1H), 7.99 (s, 1H), 8.19 (s, 1H). Separation by chiral HPLC provided additional diastereomers 10c and 10d.
