Trifluoroacetic acid → HCID 118207768, compound

Participants

Reaction Conditions

Reaction Steps

A TFA salt of 2-(1-(5-((S)-1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)pyrrolidin-3-yl)isoindoline-1,3-dione (110 mg, 0.218 mmol) was partitioned between saturated NaHCO3 and EtOAc. The aqueous and organic phases were separated and the aqueous layer was extracted with EtOAc (2×). The organic layers were combined, dried over MgSO4, and filtered, and then concentrated in a 50 mL pear flask. To this residue was added 2-amino-4-chloro-6-methylpyrimidine-5-carbonitrile (55.2 mg, 0.328 mmol) in DMSO (1.1 mL) followed by triethylamine (152 μL, 1.09 mmol). The mixture was heated to 85° C. for 3 hours and then partitioned between saturated NaHCO3 and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The organic layers were combined, dried over MgSO4, filtered, and concentrated. The crude product was purified by preparative HPLC (acid mode, 50-55% ACN/water gradient) to give the title diastereomers. Peak 1 (shorter retention time, 30 mg, 26%): 1H NMR (400 MHz, CDCl3) δ ppm 1.52 (d, J=6.57 Hz, 3H), 2.33-2.40 (m, 3H), 2.40-2.60 (m, 2H), 3.31-3.48 (m, 3H), 3.70 (t, J=8.34 Hz, 1H), 3.76-3.83 (m, 3H), 5.09-5.22 (m, 1H), 5.28 (s, 2H), 5.87-5.96 (m, 1H), 6.66 (dd, J=3.28, 0.76 Hz, 1H), 7.20-7.25 (m, 2H), 7.57 (s, 1H), 7.71-7.79 (m, 2H), 7.84-7.92 (m, 2H); ESI-MS m/z [M+H]+ calc'd for C28H27N9O2, 522. found 522. Peak 2 (longer retention time, 12 mg, 11%): ESI-MS m/z [M+H]+ calc'd for C28H27N9O2, 522. found 522.

Provenance & Evidence