Hydrochloric Acid → 4-[4-(1H-Indol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A suspension of 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (606.0 mg, 1.810 mmol, 1 eq) and 5-aminoindole (548.9 mg, 4.153 mmol, 2.3 eq) in n-BuOH (30 mL) was stirred at 120° C. for 23 h, after which it was concentrated in vacuo, to a dark brown foam. The crude material (1.2974 g) was dissolved in mixtures of DCM and MeOH (DCM alone was insufficient), to which DiPEA (0.4 mL, 2 mmol, 1 eq) was added to ensure that material was free base and not HCl salt. The crude material was adsorbed onto Hydromatrix, dry loaded, and purified by chromatography on silica gel [Jones Flashmaster, 50 g/150 mL cartridge, eluting with MeOH:DCM 1%→5% →10%]. Trituration of combined and concentrated product fractions in DCM/sonication gave the title compound as white solid. 1H NMR (400 MHz, DMSOd6): δ=1.43 (s, 9H), 2.44 (s, br, 2H), 3.55 (t, J=5.6 Hz, 2H), 4.03 (s, br, 2H), 6.35 (s, br, 1H), 6.40 (t, J=2.0 Hz, 1H), 6.67 (s, br, 1H), 7.29-7.41 (m, 3H), 8.03 (s, br, 1H), 8.19 (s, 1H), 9.14 (s, —NH), 10.99 (s, —NH), 11.81 (d, J=1.6 Hz, —NH). MS (ES+): m/z 431.04 (100) [MH+]. HPLC: tR=2.42 min (ZQ2000, polar—5 min).

Provenance & Evidence