反应详情

A mixture of 4-isopropylaniline (17.7 mg, 131 μmol), CaCO3 (33.1 mg, 331 μmol) (10 micron powder), and CH3CN (240 μL) was stirred in an ice bath for 2-3 min before adding bromoacetyl bromide (10.3 μL, 119 μmol) dropwise over 10-15 s with stirring at 0° C. After an additional 2-3 min stirring at 0° C., the ice bath was removed and the slurry was stirred at rt for 30 min. Then 6,7-dimethoxy-4-piperidin-4-yl-quinazoline (35.1 mg, 129 μmol), as prepared in Example 1d, was added in one portion and the mixture was stirred at 100° C. for 40 min. The reaction was then allowed to cool to rt, quenched with 2 M K2CO3 (2 mL), and extracted with DCM (2×2 mL). The organic layers were combined, dried (Na2SO4), and concentrated under reduced pressure. Flash chromatography of the residue (1:1 hex/acetone) provided the title compound (30.3 mg, 57%). 1H-NMR (300 MHz, CDCl3) δ 9.11 (s, 2H), 7.51 (m, 2H), 7.33 (s, 1H), 7.25 (s, 1H), 7.19 (m, 2H), 4.05 (s, 6H), 3.41 (tt, 1H), 3.21 (s, 2H), 3.18-3.10 (m, 2H), 2.88 (heptet, 1H), 2.51 (td, 2H), 2.24 (qd, 2H), 2.02-1.92 (m, 2H), 1.22 (d, 6H). LC/MS (ESI): calcd mass 448.3, found 449.3 (MH)+.

1. stirringwith stirring at 0° C
2. stirringAfter an additional 2-3 min stirring at 0° C.
3. customthe ice bath was removed
4. stirringthe slurry was stirred at rt for 30 min
5. additionwas added in one portion
6. stirringthe mixture was stirred at 100° C. for 40 min
7. customquenched with 2 M K2CO3 (2 mL)
8. extractionextracted with DCM (2×2 mL)
9. dry with materialdried (Na2SO4)
10. concentrationconcentrated under reduced pressure