* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With water In ethanol; acetone at -5 - 55℃; for 3.33333h; Heating / reflux;
1
Quinoline-3-carboxylic acid (2- {4- [2- (6, 7-dimethoxy-3, 4-dihydro-1 H- isoquinolin-2-yl)-ethyl]-phenylcarbamoyl}-4, 5-dimethoxy-phenyl)-amide (10.33g, 16mmol) was stirred in a mixture of ethanol (62 ml, 6 volumes) and demineralised water (20.6 ml, 2 volumes) and methanesulphonic acid (3. 38g, 35.2 mmol) was added. The mixture was heated to 55°C to give a clear orange coloured solution and filtered under vacuum through a preheated funnel into a dropping funnel maintained at a about 55 °C. This was followed by a 1: 1 wash of ethanol and demineralised water (2 x 20 ml, 4 volumes) at about 55°C. The combined filtrate and washes were added over about 20 minutes to stirred, refluxing acetone (310 ml, 30 volumes) to give a sticky yellow solid. After refluxing the mixture for a further 1 hour, the yellow suspension was cooled for 2 hours in an ice-bath to about-5°C. The product was collected by filtration, washed with filtered acetone (3 x 50 ml) and pulled dry for about 30 minutes. The pale yellow solid was transferred to an open dish and allowed to dry overnight in a gentle current of air at ambient temperature and humidity to give the title compound. Weight: 13. 86g ; yield: 91.5% theory for hexahydrate. The water content by Karl Fischer was 12.54% (theory for hexahydrate : 11.41%). The ratio of methanesulphonic acid to base by IH NMR was 1.93 : 1 (theory requires 2: 1). The purity by HPLC was 99.7% a/a. Elemental analyses were consistent with C38H38N406. 2CH3SO3H, 12.54% water. Found: C= 50. 35% ; H= 6.15% ; N= 5.85% ; S=6.71%. [C4oH46N4012S2, 12.54% H20 requires C= 50.09% ; H= 6.24% ; N= 5.84% ; S= 6.68%.]
A compound which is ... Quinoxaline-2-carboxylic acid (2-{4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-phenylcarbamoyl}-4,5-dimethoxy-phenyl)-amide Quinoline-3-carboxylic acid (2-{4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-phenylcarbamoyl}-phenyl)-amide Quinoline-3-carboxylic acid (2-{4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-phenylcarbamoyl}-5-fluoro-phenyl)-amide Quinoline-3-carboxylic acid (2-{4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-phenylcarbamoyl}-4-fluoro-phenyl)-amide Quinoline-3-carboxylic acid (2-{4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-phenylcarbamoyl}-4,5-dimethoxy-phenyl)-amide Quinoline-3-carboxylic acid (6-{4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-phenylcarbamoyl}-benzo[1,3]dioxol-5-yl)-amide Quinoline-3-carboxylic acid (2-{4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-phenylcarbamoyl}-5-nitro-phenyl)-amide Quinoline-3-carboxylic acid (2-{4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-phenylcarbamoyl}-4-methyl-phenyl)-amide ...
3
[ 849668-91-3 ]
[ 84741-86-6 ]
[ 206873-63-4 ]
Yield
Reaction Conditions
Operation in experiment
75%
In dichloromethane at 20℃; for 24h;
4.1.6. General procedures E for the preparation of the amide bonds19-24
General procedure: The aromatic amine (30) (1 eq.) and NEt3 (3 eq.) were dissolvedin CH2Cl2, and the aromatic carbonyl chloride (1.5 eq.) derived fromthe corresponding acid via general procedure Awas added in smallportions. The solution was stirred at room temperature for 24 h,diluted with CH2Cl2, washed with water and saturated aqueoussolution of Na2CO3 (3), dried over MgSO4, and concentrated togive the crude product, which was purified by column chromatographyusing silica gel or recrystallization.
With ammonia; triethylamine In tetrahydrofuran; ethanol at 50℃;
1.E Step E
To a solution of compound 7 is added Compound 8 in the presence of tetrahydrofuran, triethylamine; ammonia, and ethanol at 50° C. and allowed to react to form compound 9 (tariquidar). The resultant slurry is cooled to 0° C. and stirred for 1 h. The solid is filtered and washed with hexanes (2×500 mL) and air dried overnight.
In tetrahydrofuran; butanone at 80℃; Inert atmosphere;
23 Example 23: 2-(3-(3-((((9H-fluorene-9-yl)methoxy)carbonyl)amino)propaneamido)-4-(((3R,4S,5S,6S)-3,4,5-triacetoxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl) oxy)benzyl)-2-(4-(4,5-dimethoxy-2-(quinoline-3-carboxamido)benzamido)phenethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-ium 34
A pressure vessel was charged with the brominated stretcher-glucuronide unit intermediate of Example 1 (2, 78 mg, 96 μmol) and anhydrous 2-butanone Was charged to Tariquidar (33, 62 mg, 96 μmol) in tetrahydrofuran (2.9 mL). The reaction vessel was then purged with nitrogen and sealed . The reaction was then stirred and heated to 80 & lt; 0 & gt; C for 4 h, at which time LC / MS was converted to the quaternized product Respectively. The resultant was cooled, condensed under reduced pressure and purified by preparative HPLC to give 34 (123 mg, 90%)