Monocarboxylate transport modulators and uses thereof
一种选自、药学的技术，应用在单羧酸转运蛋白调节剂及其用途领域，能够解决没有应用癌症治疗等问题
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0313]
[0314] step 1
[0315]
[0316] method
[0317] In a 250 mL 3-necked round bottom flask, 3-chloro-4-fluoroaniline (20 g, 137.4 mmol) and toluene (100 mL) were added. To the reaction mixture was added diethyl-2-(ethoxymethylene)malonate (29.7 g, 137.4 mmol) at 25°C. The reaction mixture was heated at reflux and stirred for 1 h, then cooled to 30 °C and water (150 mL) was added and the mixture was extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine solution, washed with anhydrous Na 2 SO 4 Drying and concentration under reduced pressure afforded 40 g of crude product which was titrated with a minimal amount of cyclohexane to give diethyl-2-(3-chloro-4-fluorophenylamino)methylenemalonate (1) 36g, yield (50.1%); 1 H NMR (400MHz, DMSO-d 6): δ10.61(d, J=12.8,1H),8.29(d,J=13.6,1H),7.72-7.74(m,1H),7.4-7.42(m,2H),4.12-4.2(m, 4H), 1.24-1.26 (m, 6H); MS (ESI): 316.1 (M+H).
[0318] step 2
[0319]
[0320] In a 500 mL 3-neck rou...
Embodiment 2
[0331] The remaining mother liquor from the synthesis of Example 1 was concentrated under reduced pressure to obtain crude 5b. The product was purified by column chromatography (silica gel) to obtain 10 mg of pure 6-(benzyl(methyl)amino)-7-chloro-1-isobutyl-4-oxo-1,4-dihydroquinoline- 3-Carboxylic acid (5b): yield, 5%; 1 H NMR (400MHz, DMSO-d 6 ):δ15.16(d,1H),8.95(s,1H),7.28-8.27(m,7H),4.41-4.43(d,2H),4.3(s,2H),2.74(s,3H), 2.1-2.2 (m, 1H), 0.88-0.90 (d, 6H); MS (ESI): 399 (M+H); HPLC: 93.57%.
Embodiment 3
[0333]
[0334] In a 25 mL single necked round bottom flask were added intermediate 4 (0.5 g, 1.679 mmol) from Example 1 and N-1-(3-(trifluoromethyl)phenyl)methanamine (1.5 g, 8.39 mmol) ) and heated to 120°C for 24h. The reaction was monitored for completion by TLC, worked up aqueous and acidified to pH 3-4 with 1 N HCl. The aqueous layer was extracted with EtOAc and the organic layer was washed with anhydrous Na 2 SO 4 dry. The solvent was evaporated under reduced pressure to obtain a crude product which was purified by silica gel column chromatography to obtain pure 6-fluoro-1-isobutyl-7-(methyl(3-(trifluoromethyl)benzyl) Amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (5), (25mg); Yield: 3.3%; 1 H NMR (400MHz, DMSO-d 6 ):δ15.5(s,1H),6.83-8.71(m,7H),4.75(s,2H),4.20(d,2H),3.13(s,3H),1.83-1.86(m,1H), 0.74-0.76 (d,6H); MS (ESI): 451.1 (M+H); HPLC: 92.07%.
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More 
PatSnap Eureka turns technology decisions into work you can execute. Powered by our Innovation Knowledge Graph, it runs expert workflows across engineering, life sciences, materials and intellectual property. Get your review-ready output in minutes.
