1-Hydroxybenzotriazole → 1-[4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3,6-dihydro-2H-pyridin-1-yl]-3-piperidin-1-ylpropan-1-one

Participants

Reaction Steps

To a suspension/solution of 4-chloro-6-(1,2,3,6-tetrahydropyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidine bis-hydrochloride (19.1 mg, 0.0621 mmol, 1 eq), 1-piperidinepropanoic acid (24.5 mg, 0.156 mmol, 2.5 eq), 1-hydroxybenzotriazole (HOBt) (8.5 mg, 0.063 mmol, 1 eq), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) (36.3 mg, 0.189 mmol, 3 eq) in anhydrous DMF (1.3 mL), DiPEA (64 μL, 0.37 mmol, 6 eq) was added and the reaction was stirred at rt, under N2, for 16 h. Solvent was concentrated in vacuo and the residue was dissolved in DCM, washed with NaHCO3 (2×) and brine (1×), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified on MDPS giving the title compound as a yellow solid. 1H NMR (400 MHz, MeOH-d4): δ=1.45-1.56 (s, br, 2H), 1.64 (sextet, J=5.6 Hz, 4H), 2.46-2.78 (m, 10H), 3.81 & 3.84 (t, J=5.6 Hz, rotamers, 2H), 4.29 & 4.33 (d, J=2.0 Hz, rotamers, 2H), 6.48 (s, br, 1H), 6.62 & 6.63 (s, rotamers, 1H), 8.50 (d, 1H). MS (ES+): m/z 373.99/376.00 (100/36) [MH+]. HPLC: tR=1.86 min (ZQ2000, polar—5 min).

Provenance & Evidence