Compounds and use for treating cancer
A compound, technology of use, applied in the field of compound for treating cancer and its use
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1Va
[0442] Synthesis of Example 1 Vacquinol-1 (S10, NSC13316). General Method A.
[0443]
[0444] Reaction conditions: (a) (4-chlorophenyl) acetophenone, KOH, EtOH, 51%; (b) MeOH, H 2 SO 4 ,57%; (c)8,NaNH 2 , Benzene, 14%; (d) HCl, NaOH, 63%; (e) Br 2 , HBr, 68%; (f) Na 2 CO 3 , EtOH, 55%; (g) EtOH, NaBH 4 ,66%. Synthesis of methyl 6-benzoylaminocaproate (8): (h)SOCl 2 , MeOH, 99%; (i) Benzoic acid, EDCI, HOBt, DIPEA, 63%.
[0445] 2-(4-Chlorophenyl)quinoline-4-carboxylic acid (Intermediate 1). 4-Chloroacetophenone (47.0 g, 244 mol) was added to isatin (30.0 g, 204 mmol) in one addition Stirred solution in 500 mL of ethanol. Potassium hydroxide pellets (22.8 g, 408 mmol) were added in portions and the reaction was heated to reflux for 14 hours. The reaction was diluted with 1 L of water and washed with ethyl acetate (3 x 300 mL). The aqueous layer was cooled in an ice bath and acidified with glacial acetic acid. The precipitated product was filtered, washed with co...
Embodiment 2
[0454] Example 2. Synthesis of Vacquinol-1 (S10, NSC13316). General Method B.
[0455]
[0456] Reaction conditions: (a) N-Boc-piperidine, sec-BuLi, TMEDA, THF, 27%; (b) NaBH 4 , EtOH, 72%; (c) HCl, Et 2 O, MeOH, 80%.
[0457] tert-Butyl 2-(2-phenylquinoline-4-carbonyl)piperidine-1-carboxylate (Intermediate 9) TMEDA (2 mL) and sec-butyllithium (1.4 M in cyclohexane, 5 mL, 7.06 mmol) was added dropwise to a stirred solution of tert-butyl piperidine-1-carboxylate (1.0 g, 5.4 mmol) in dry THF (30 mL) cooled to 0 °C and stirring continued for 2 hours. A solution of compound 2 (1.42 g, 5.43 mmol) in dry THF (30 mL) was added to the reaction mixture and stirring was continued at 0 °C for an additional 2 hours. The reaction mixture was slowly warmed to RT and stirred for 3 hours (monitored by TLC). After complete consumption of the starting material; the reaction mixture was quenched with saturated ammonium chloride solution (40 mL) and extracted with EtOAc (2 x 40 mL). The c...
Embodiment 3
[0460] The synthesis of embodiment 3.S14
[0461]
[0462] Reaction conditions: (a) NaBH4, EtOH, 72%; (b) NaH, MeI, DMF, 63%; (c) HCl, dioxane, 36%.
[0463] tert-Butyl 2-((2-(4-chlorophenyl)quinolin-4-yl)(hydroxy)methyl)piperidine-1-carboxylate (Intermediate 10) was prepared as described in Example 2 preparation.
[0464] 2-((2-(4-chlorophenyl)quinolin-4-yl)(methoxy)methyl)piperidine-1-carboxylic acid tert-butyl ester (Intermediate 11).Sodium hydride (18.5mg , 0.46 mmol) was added to a stirred solution of intermediate 10 (140 mg, 0.31 mmol) in DMF (1 mL) cooled to 0 °C under an inert atmosphere and stirring continued for 10 min. Methyl iodide (0.023 mL, 0.371 mmol) was added to the reaction mixture which was slowly warmed to room temperature and stirring continued for 1 hour (monitored by TLC). After complete consumption of starting material; the reaction mixture was diluted with water (10 mL) and extracted with EtOAc (2 x 25 mL). The combined organic extracts were was...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More