反应详情

Portions of 0.4 mL of a 1 M solution of SO2Cl2 in DCM are added repeatedly over a period of 27 h to an ice-cooled suspension of 3-(5-methoxy-3-trifluoromethyl-phenyl)-1-{6-[4-(4-ethylpiperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (105 mg, 0.20 mmol) (Example 26) in acetonitrile (6 mL). The reaction is followed by HPLC analysis. The reaction mixture (still containing starting material) is diluted with DCM and a saturated aqueous solution of NaHCO3. The aqueous layer is separated and extracted twice with DCM. The organic phases are washed with brine, dried (Na2SO4), filtered and concentrated. Reversed phase MPLC (H2O/CH3CN+0.1% TFA) yields, after neutralization of the product containing fractions with NaHCO3, partial concentration and extraction with DCM, the title compound: API-MS: 564/566 [MH]+; TLC: Rf=0.28 (DCM/MeOH+1% NH3aq, 95:5); 1H-NMR (DMXO-d6) δ 1.02 (t, H3C), 2.37 (q, H2C), 2.51 (m, 4H), 2.92 (m, 4H), 3.33 (s, H3C), 3.82 (s, H3C), 6.48 (s, 1H), 6.90 (s, 1H), 7.12 (d, 1H), 7.43 (m, 2H), 7.59 (s, 1H), 7.82 (s, 1H), 8.55 (s, 1H), 9.66 (s, HN), 12.33 (s, HN).

1. temperaturecooled
2. additionThe reaction mixture (still containing starting material)
3. customThe aqueous layer is separated
4. extractionextracted twice with DCM
5. washThe organic phases are washed with brine
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customReversed phase MPLC (H2O/CH3CN+0.1% TFA) yields
10. additionafter neutralization of the product containing fractions
11. concentrationwith NaHCO3, partial concentration and extraction with DCM