反应详情

A solution of diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (50.0 mg, 0.110 mmol) and 2-amino-5-fluoro-N-methylbenzamide (Compound 102A, 22.24 mg, 0.1322 mmol) in TFE (1.00 mL) was charged with TFA (37.7 mg, 0.330 mmol). The reaction mixture was irradiated on the microwave at 105° C. for 1 hour. The reaction mixture was concentrated under reduced pressure to yield a yellow oil. The material was purified by silica gel chromatography on an ISCO Combi-flash Rf system using DCM/MeOH (100:0→95:5) as eluent. The fractions containing product were combined and concentrated under reduced pressure to yield a white solid, 21.4 mg (33% yield). The material still contained impurities, therefore was submitted for mass directed purification. The fractions containing product were combined and dried on the freeze dryer to yield a white solid, 10.9 mg (17% yield). 1H NMR (DMSO-d6, 400 MHz): δ=1.19 (t, J=7.07 Hz, 6 H), 2.76 (d, J=4.55 Hz, 3 H), 3.21-3.28 (m, 2 H), 3.76 (s, 3 H), 3.92-4.04 (m, 4 H), 6.84 (d, J=6.57 Hz, 1 H), 7.01 (br. s., 1 H), 7.24 (br. s., 1 H), 7.38-7.65 (m, 2 H), 8.24-8.55 (m, 2 H), 8.79 (br. s., 2 H), 11.25 (br. s., 1 H). MS (ES+): m/z 586.19 [MH+] (TOF, polar).

1. customThe reaction mixture was irradiated on the microwave at 105° C. for 1 hour
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. customto yield a yellow oil
4. customThe material was purified by silica gel chromatography on an ISCO Combi-flash Rf system
5. additionThe fractions containing product
6. concentrationconcentrated under reduced pressure
7. customto yield a white solid, 21.4 mg (33% yield)
8. custompurification
9. additionThe fractions containing product
10. customdried on the freeze dryer
11. customto yield a white solid, 10.9 mg (17% yield)