A kind of hedgehog pathway inhibitor and its preparation method and application

[0042]

[0043] (1) Lithium diisopropylamide (LDA, 150mL, 2mol, in tetrahydrofuran) was added dropwise to tetrahydrofuran (500mL), cooled to -78°C, and ethyl isobutyrate (formula (2), 33 g , 0.284mol), the reaction mixture was kept at -70 to -65°C for 20 minutes, and then 2,3-dichloropropene (31 g, 0.279mol) was added dropwise. After the addition was completed, the reaction solution was gradually warmed to room temperature for 18 hours After the reaction was completed, it was quenched with saturated ammonium chloride, extracted twice with dichloromethane (2×300mL), the combined organic layer was dried over anhydrous sodium sulfate, filtered and rotary evaporated to obtain a brown oil compound 4-chloro-2, Ethyl 2-dimethyl-4-pentenoate (formula (3), 59 g, 0.279 mol, 93% yield) was directly used in the next reaction. Formula (3) 1 H NMR (400MHz, CDCl 3 ): δ (ppm) 1.24-1.28 (m, 9H), 2.65 (s, 2H), 4.15 (q, 4H), 5.13 (s, 1H), 5.24 (s, 1H).

[0044] (2) 4-chloro-2,2-dimethyl-4-pen

[0053] This example is used to illustrate the effect of the compound of formula (1) of the present invention on tumor proliferation associated with the activation of hedgehog pathway.