反应详情

Diethyl(4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (30.0 mg, 0.0661 mmol) and 3-amino-N-methylpyridine-2-carboxamide (Compound 231C, 15.0 mg, 0.0992 mmol) were taken up in TFE (2.7 mL, 37 mmol) and treated with TFA (15.3 uL, 0.198 mmol). This mixture was irradiated on the CEM for 120 min at 100° C. R×n mixture was poured into water and extracted twice with EtOAc. The combined organic layers were dried over Na2SO4, filtered, concentrated and purified on an ISCO CombiFlash system (eluting with 0-4% MeOH/DCM) to isolate, after concentrating the relevant fractions and drying in vacuo, the desired product as 20.8 mg of a white solid. 1H NMR (400 MHz, DMSO-d6) δ1.19 (t, J=7.07 Hz, 6H), 2.81 (d, J=4.80 Hz, 3H), 3.28 (d, J=20.50 Hz, 2H), 3.74 (s, 3H), 3.94-4.04 (m, 4H), 6.90 (dt, J=8.15, 1.99 Hz, 1H), 7.05 (s, 1H), 7.33-7.51 (m, 2H), 8.21 (d, J=3.54 Hz, 1H), 8.41 (s, 1H), 9.08 (br. s., 1H), 9.11 (q, J=4.21 Hz, 1H), 12.45 (s, 1H). MS (ES+): m/z=569.10 (100) [M+1]. HPLC: tR=1.52 min (UPLC TOF, polar—3 min).

1. customThis mixture was irradiated on the CEM for 120 min at 100° C
2. extractionextracted twice with EtOAc
3. dry with materialThe combined organic layers were dried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. custompurified on an ISCO CombiFlash system (eluting with 0-4% MeOH/DCM)
7. customto isolate
8. concentrationafter concentrating the relevant fractions
9. customdrying in vacuo
10. customHPLC: tR=1.52 min (UPLC TOF, polar—3 min)