Potassium Phosphate, Tribasic → HCID 66990986, compound

Participants

Reaction Conditions

Reaction Steps

Racemic (3S,5R)-1-[6-chloro-2-(methylamino)-4-pyrimidinyl]-5-methyl-N-(phenylmethyl)-3-pyrrolidinecarboxamide (100 mg, 0.28 mmol), (4-cyano-3-fluorophenyl)boronic acid (60 mg, 0.36 mmol, 1.3 equiv), tricyclohexylphosphine (12 mg, 0.043 mmol, 0.15 equiv), Pd2(dba)3 (20 mg, 0.022 mmol, 0.075 equiv) and K3PO4 (101 mg, 0.48 mmol, 1.7 equiv) were charged to a 20 mL microwave vial, followed by addition of 1,4-dioxane (3 mL) and water (1 mL). The mixture was bubbled with argon for 15 minutes, followed by capping and heating to 100° C. for 21 hours. This crude mixture was combined with another run starting with 300 mg of racemic (3S,5R)-1-[6-chloro-2-(methylamino)-4-pyrimidinyl]-5-methyl-N-(phenylmethyl)-3-pyrrolidinecarboxamide. The combined mixture was filtered through celite, and the cake was rinsed with EtOAc (100 mL). The filtrate was concentrated in vacuo, and the resulting residue was taken up in 25 mL of water, sonicated briefly, and filtered. The dark colored solids were washed with water, and dried under house vacuum for 1 hour. Attempt was made to dissolve these solids in CHCl3, EtOAc, and CH3OH, but there was always some residue left. The residue was checked by LCMS be the pure desired product. This dark colored residue was collected by filtration, and dissolved in CHCl3 with a small amount of MeOH (2% by volume, total solvent used about 100 mL) to give a dark solution, which was filterd through celite. The filtrate was concentrated in vacuo, and the resulting yellowish residue was dried under vacuum to give 142 mg of the title compound. The above organic filtrate (combined CHCl3, EtOAc and CH3OH wash) was concentrated in vacuo. Trituration in EtOAc (6 mL) and drying under vacuum gave another 220 mg of the title compound.

Provenance & Evidence