5-Amino-2-fluoropyridine → HCID 178439371, compound

Participants

Reaction Steps

To a stirred solution of 5-amino-2-fluoropyridine (79 mg, 0.703 mmol) in dry THF (2 mL) was added isopropyl magnesium chloride 2M in THF (0.43 mL, 0.86 mmol) dropwise under nitrogen atmosphere at 0° C. The resultant mixture was stirred at 0° C. for 30 min. To this was added a solution of (S)-methyl 1-(4-(3-isopropyl-1H-pyrazol-5-ylamino)-6,6-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxylate (70 mg, 0.175 mmol) in THF (2 mL) dropwise at 0° C. and the reaction mixture was allowed to stir at RT for 2 h. The reaction mixture was cooled to 0° C. and quenched by saturated ammonium chloride solution (10 mL). The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (2×20 mL). The organic layer was washed with brine (20 mL) and dried over anhydrous sodium sulfate. Removal of EtOAc under vacuum gave a crude oil which was purified by reverse phase HPLC to afford 15 mg of (S)—N-(6-fluoropyridin-3-yl)-1-(4-(3-isopropyl-1H-pyrazol-5-ylamino)-6,6-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide. 1H NMR (400 MHz, CD3OD, freebase) δ (ppm): 1.15-1.25 (m, 6H), 1.20 (s, 6H), 2.02-2.18 (m, 2H), 2.22-2.3.8 (m, 2H), 2.58 (s, 2H), 2.62 (s, 2H), 2.79-2.90 (m, 1H), 3.60-3.70 (m, 1H), 3.78-3.87 (m, 1H), 4.77 (dd, 1H), 6.25 (brs, 1H), 6.99 (dd, 1H), 7.97 (brs, 1H), 8.20 (s, 1H). The other enantiomer was obtained using the chiral (R) starting material.

Provenance & Evidence