Ammonia → N-(3-(2-methyl-9H-purin-6-yl)pyridin-2-yl)-1H-indol-4-amine

Participants

Reaction Conditions

Reaction Steps

6-(2-Fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (270 mg, 0.862 mmol) and 4 aminoindole (159.3 mg, 1.205 mmol) were suspended in EtOH (5.0 mL) and then aqueous hydrochloric acid, (5 N, 0.21 mL, 1.1 mmol) was added. The reaction flask was fit with a reflux condenser, placed in a preheated oil bath (100° C.), and stirred for 3 hours. Then, the reaction was cooled to room temperature, diluted with 2 N ammonia in MeOH (4.0 mL), and allowed to stand overnight. Then, the material was concentrated, treated with DMF and filtered. The solid was washed with DCM, and the filtrate was concentrated and purified on prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 mL/min). The fractions with product were collected, concentrated, and filtered through a silica gel plug (about 1 inch) with 10:1 DCM/2 N ammonia in MeOH to give N-(3-(2-methyl-9H-purin-6-yl)pyridin-2-yl)-1H-indol-4-amine (13.7 mg, 5%). MS (ESI pos. ion) m/z 342 (M+H)+. 1H NMR (d6-DMSO, 400 MHz) δ 13.60 (s, 1H), 12.44 (s, 1H), 11.16 (s, 1H), 9.77 (d, J=7.04 Hz, 1H), 8.61 (s, 1H), 8.37 (dd, J=4.69 Hz, 1.76 Hz, 1H), 8.05 (dd, J=6.85 Hz, 1.56 Hz, 1H), 7.37 (t, J=2.64 Hz, 1H), 7.11-7.04 (m, 2H), 7.01 (dd, J=7.82 Hz, 4.69 Hz, 1H), 6.72 (s, 1H), 2.92 (s, 3H).

Provenance & Evidence