反应详情

温度

100 °C

6-(2-Fluoropyridin-3-yl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (115.0 mg, 0.3842 mmol) and 1H-indol-4-amine (Aldrich, St. Louis, Mo., 70.7 mg, 0.535 mmol) were suspended in EtOH (1.8 mL) and aqueous hydrochoric acid (5.0 M, 0.090 ml, 0.45 mmol) was added. The flask was fitted with a reflux condenser and placed in a preheated oil bath (100° C.), and the reaction was stirred for 3 hours. Then, the reaction was cooled to room temperature and diluted with DCM, 2N ammonia in MeOH, EtOH, and MeOH and concentrated. The residue was treated with MeOH and filtered. Neither the filtrate nor the solid contained pure material, so they were combined, concentrated, treated with DMF, and filtered. The filtrate was concentrated and purified on 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, 50:1 DCM/2N ammonia in MeOH to 20:1 DCM/2N ammonia in MeOH to 5:1 DCM/2N ammonia in MeOH) to afford N-(3-(9H-purin-6-yl)pyridin-2-yl)-1H-indol-4-amine (6.9 mg, 5% yield). MS (ESI pos. ion) m/z: 328, (M+H)+. 1H NMR (d6-DMSO, 400 MHz) δ 12.90 (s, 1H), 11.16 (s, 1H), 9.87 (d, J=7.82 Hz, 1H), 9.24 (s, 1H), 8.73 (s, 1H), 8.43 (dd, J=4.69 Hz, 1.96 Hz, 1H), 8.28 (dd, J=4.6 Hz, 3.81 Hz, 1H), 7.38-7.35 (m, 1H), 7.09 (s, 1H), 7.08-7.06 (m, 1H), 7.04 (dd, J=7.82 Hz, 4.69 Hz, 1H), 6.79-6.76 (m, 1H).

1. customThe flask was fitted with a reflux condenser
2. customplaced in a preheated oil bath
3. temperatureThen, the reaction was cooled to room temperature
4. concentrationconcentrated
5. additionThe residue was treated with MeOH
6. filtrationfiltered
7. concentrationconcentrated
8. additiontreated with DMF
9. filtrationfiltered
10. concentrationThe filtrate was concentrated
11. custompurified on HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 mL/min)
12. customThe fractions with product were collected
13. concentrationconcentrated
14. filtrationfiltered through a silica gel plug (about 1 inch, 50:1 DCM/2N ammonia in MeOH to 20:1 DCM/2N ammonia in MeOH to 5:1 DCM/2N ammonia in MeOH)