Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 168626-94-6 | MDL No. : | MFCD00945712 |
Formula : | C32H27ClN4O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | BTYHAFSDANBVMJ-UHFFFAOYSA-N |
M.W : | 535.04 | Pubchem ID : | 216322 |
Synonyms : |
YM 087;Conivaptan (hydrochloride);Conivaptan HCl
|
Chemical Name : | N-(4-(2-Methyl-1,4,5,6-tetrahydrobenzo[b]imidazo[4,5-d]azepine-6-carbonyl)phenyl)-[1,1'-biphenyl]-2-carboxamide hydrochloride |
Num. heavy atoms : | 39 |
Num. arom. heavy atoms : | 29 |
Fraction Csp3 : | 0.09 |
Num. rotatable bonds : | 6 |
Num. H-bond acceptors : | 3.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 160.51 |
TPSA : | 78.09 Ų |
GI absorption : | Low |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | Yes |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | Yes |
Log Kp (skin permeation) : | -4.97 cm/s |
Log Po/w (iLOGP) : | 0.0 |
Log Po/w (XLOGP3) : | 6.47 |
Log Po/w (WLOGP) : | 6.74 |
Log Po/w (MLOGP) : | 4.26 |
Log Po/w (SILICOS-IT) : | 6.04 |
Consensus Log Po/w : | 4.7 |
Lipinski : | 2.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 1.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.17 |
Log S (ESOL) : | -7.39 |
Solubility : | 0.0000219 mg/ml ; 0.000000041 mol/l |
Class : | Poorly soluble |
Log S (Ali) : | -7.91 |
Solubility : | 0.00000666 mg/ml ; 0.0000000124 mol/l |
Class : | Poorly soluble |
Log S (SILICOS-IT) : | -11.35 |
Solubility : | 0.0000000024 mg/ml ; 0.0 mol/l |
Class : | Insoluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 4.05 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P201-P202-P280-P308+P313-P405-P501 | UN#: | N/A |
Hazard Statements: | H361 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | Stage #1: 2-Biphenylcarboxylic acid With pyridine; oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide Stage #2: {4-[(2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl)carbonyl]phenyl}amine With pyridine In dichloromethane; N,N-dimethyl-formamide; acetonitrile Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: 28 percent / potassium carbonate / CHCl3 / 96 h / Heating 2.1: 61 percent / cc. sulfuric acid / acetic acid / 51 h / 70 °C 3.1: 73 percent / pyridine monohydrochloride / dimethylformamide / 3 h / 25 °C 4.1: 94 percent / H2 / Raney nickel / methanol / 1 h / 25 °C 5.1: oxalyl chloride; pyridine / dimethylformamide; CH2Cl2 5.2: 74 percent / pyridine / dimethylformamide; CH2Cl2; acetonitrile / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1.1: 98 percent / potassium carbonate; potassium iodide / butan-2-one / 12 h / Heating 2.1: 93 percent / potassium t-butoxide / dimethylformamide / 2 h / 0 - 5 °C 3.1: 97 percent / acetic acid; cc. HCl / 11 h / 80 °C 4.1: 89 percent / pyridinium hydrobromide perbromide / CHCl3 / 1 h / 15 - 30 °C 5.1: 28 percent / potassium carbonate / CHCl3 / 96 h / Heating 6.1: 61 percent / cc. sulfuric acid / acetic acid / 51 h / 70 °C 7.1: 73 percent / pyridine monohydrochloride / dimethylformamide / 3 h / 25 °C 8.1: 94 percent / H2 / Raney nickel / methanol / 1 h / 25 °C 9.1: oxalyl chloride; pyridine / dimethylformamide; CH2Cl2 9.2: 74 percent / pyridine / dimethylformamide; CH2Cl2; acetonitrile / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: 97 percent / acetic acid; cc. HCl / 11 h / 80 °C 2.1: 89 percent / pyridinium hydrobromide perbromide / CHCl3 / 1 h / 15 - 30 °C 3.1: 28 percent / potassium carbonate / CHCl3 / 96 h / Heating 4.1: 61 percent / cc. sulfuric acid / acetic acid / 51 h / 70 °C 5.1: 73 percent / pyridine monohydrochloride / dimethylformamide / 3 h / 25 °C 6.1: 94 percent / H2 / Raney nickel / methanol / 1 h / 25 °C 7.1: oxalyl chloride; pyridine / dimethylformamide; CH2Cl2 7.2: 74 percent / pyridine / dimethylformamide; CH2Cl2; acetonitrile / Heating | ||
Multi-step reaction with 6 steps 1.1: acetic acid; hydrogenchloride / water / 10 h / Reflux 2.1: triethylamine / dichloromethane / 2 h / 25 °C 3.1: bromine / chloroform / 1 h / 5 - 30 °C 4.1: potassium carbonate / chloroform / 18 h / Reflux 5.1: hydrogen / methanol; N,N-dimethyl-formamide / 1 h / 25 °C 6.1: pyridine / acetonitrile / 0 - 25 °C / Reflux 6.2: 0.5 h / 5 - 30 °C | ||
Multi-step reaction with 7 steps 1: acetic acid; hydrogenchloride / water / 10 h / Reflux 2: triethylamine / dichloromethane / 2 h / 25 °C 3: hydrogen; palladium on activated charcoal / ethanol 4: triethylamine / dichloromethane 5: copper(ll) bromide / chloroform; ethyl acetate 6: potassium carbonate / acetonitrile 7: hydrogenchloride / ethanol; ethyl acetate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: 73 percent / pyridine monohydrochloride / dimethylformamide / 3 h / 25 °C 2.1: 94 percent / H2 / Raney nickel / methanol / 1 h / 25 °C 3.1: oxalyl chloride; pyridine / dimethylformamide; CH2Cl2 3.2: 74 percent / pyridine / dimethylformamide; CH2Cl2; acetonitrile / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1.1: 100 percent / pyridine / 25 °C 2.1: 98 percent / potassium carbonate; potassium iodide / butan-2-one / 12 h / Heating 3.1: 93 percent / potassium t-butoxide / dimethylformamide / 2 h / 0 - 5 °C 4.1: 97 percent / acetic acid; cc. HCl / 11 h / 80 °C 5.1: 89 percent / pyridinium hydrobromide perbromide / CHCl3 / 1 h / 15 - 30 °C 6.1: 28 percent / potassium carbonate / CHCl3 / 96 h / Heating 7.1: 61 percent / cc. sulfuric acid / acetic acid / 51 h / 70 °C 8.1: 73 percent / pyridine monohydrochloride / dimethylformamide / 3 h / 25 °C 9.1: 94 percent / H2 / Raney nickel / methanol / 1 h / 25 °C 10.1: oxalyl chloride; pyridine / dimethylformamide; CH2Cl2 10.2: 74 percent / pyridine / dimethylformamide; CH2Cl2; acetonitrile / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: 93 percent / potassium t-butoxide / dimethylformamide / 2 h / 0 - 5 °C 2.1: 97 percent / acetic acid; cc. HCl / 11 h / 80 °C 3.1: 89 percent / pyridinium hydrobromide perbromide / CHCl3 / 1 h / 15 - 30 °C 4.1: 28 percent / potassium carbonate / CHCl3 / 96 h / Heating 5.1: 61 percent / cc. sulfuric acid / acetic acid / 51 h / 70 °C 6.1: 73 percent / pyridine monohydrochloride / dimethylformamide / 3 h / 25 °C 7.1: 94 percent / H2 / Raney nickel / methanol / 1 h / 25 °C 8.1: oxalyl chloride; pyridine / dimethylformamide; CH2Cl2 8.2: 74 percent / pyridine / dimethylformamide; CH2Cl2; acetonitrile / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: 73 percent / pyridine monohydrochloride / dimethylformamide / 3 h / 25 °C 2.1: 94 percent / H2 / Raney nickel / methanol / 1 h / 25 °C 3.1: oxalyl chloride; pyridine / dimethylformamide; CH2Cl2 3.2: 74 percent / pyridine / dimethylformamide; CH2Cl2; acetonitrile / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: 61 percent / cc. sulfuric acid / acetic acid / 51 h / 70 °C 2.1: 73 percent / pyridine monohydrochloride / dimethylformamide / 3 h / 25 °C 3.1: 94 percent / H2 / Raney nickel / methanol / 1 h / 25 °C 4.1: oxalyl chloride; pyridine / dimethylformamide; CH2Cl2 4.2: 74 percent / pyridine / dimethylformamide; CH2Cl2; acetonitrile / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: 94 percent / H2 / Raney nickel / methanol / 1 h / 25 °C 2.1: oxalyl chloride; pyridine / dimethylformamide; CH2Cl2 2.2: 74 percent / pyridine / dimethylformamide; CH2Cl2; acetonitrile / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18 EXAMPLE 18 4'-[(2-Methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)carbonyl]-2-phenylbenzanilide was dissolved in 5 ml of ethyl alcohol, the resulting solution was mixed with 0.19 ml of 4N hydrochloric acid-ethyl acetate and cooled on an ice bath and then the thus precipitated crystals were collected by filtration and washed with a small volume of ethyl alcohol to obtain 220 mg of 4'-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)carbonyl]-2-phenylbenzanilide hydrochloride (Example 18(2)). | ||
41 EXAMPLE 41 This compound was crystallized from 31.5 ml of ethyl alcohol and 27.2 ml of 1N hydrochloric acid to obtain crude crystals (B crystal) of 4'-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)carbonyl]-2-phenylbenzanilide hydrochloride. These crystals were suspended in 45 ml of acetonitrile, heated for 30 minutes under reflux, cooled down, collected by filtration and then dried to obtain crude crystals (γ crystal). Thereafter, they were suspended in 26 ml of ethyl alcohol, heated for 30 minutes under reflux, cooled down, collected by filtration and then dried to obtain 1.6 g of 4'-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)carbonyl]-2-phenylbenzanilide hydrochloride in the form of crystals (α crystal). Physicochemical properties (α crystal) Melting point: >300° C. 1H-NMR (δ ppm in DMSO-d6, TMS internal standard): 2.66 (3H, s), 3.00 (1H, t), 4.99 (1H, m), 6.89 (2H), 7.14 (1H, t), 8.02 (1H, d), 10.31 (1H, s), 14.6 (1H, br) MS (EI): 498 (M+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: potassium carbonate / chloroform / 18 h / Reflux 2.1: hydrogen / methanol; N,N-dimethyl-formamide / 1 h / 25 °C 3.1: pyridine / acetonitrile / 0 - 25 °C / Reflux 3.2: 0.5 h / 5 - 30 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: hydrogen / methanol; N,N-dimethyl-formamide / 1 h / 25 °C 2.1: pyridine / acetonitrile / 0 - 25 °C / Reflux 2.2: 0.5 h / 5 - 30 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | Stage #1: o-phenylbenzoyl chloride; {4-[(2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl)carbonyl]phenyl}amine With pyridine In acetonitrile at 0 - 25℃; Reflux; Stage #2: With hydrogenchloride In ethyl acetate; acetonitrile at 5 - 30℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / -15 - 25 °C 2.1: pyridine / acetonitrile / 0 - 25 °C / Reflux 2.2: 0.5 h / 5 - 30 °C | ||
Multi-step reaction with 5 steps 1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / -15 - 25 °C 2: triethylamine / dichloromethane 3: copper(ll) bromide / chloroform; ethyl acetate 4: potassium carbonate / acetonitrile 5: hydrogenchloride / ethanol; ethyl acetate | ||
Multi-step reaction with 3 steps 1: thionyl chloride; N,N-dimethyl-formamide / toluene / 2 h / 40 °C 2: <i>N</i>,<i>N</i>-dimethyl-aniline / acetone / 2 h / 25 °C 3: ethyl [2]alcohol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: triethylamine / dichloromethane 2: copper(ll) bromide / chloroform; ethyl acetate 3: potassium carbonate / acetonitrile 4: hydrogenchloride / ethanol; ethyl acetate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: triethylamine / dichloromethane 2: copper(ll) bromide / chloroform; ethyl acetate 3: potassium carbonate / acetonitrile 4: hydrogenchloride / ethanol; ethyl acetate | ||
Multi-step reaction with 3 steps 1.1: iodine; phosphorous acid trimethyl ester; N-ethyl-N,N-diisopropylamine / chloroform / 0.17 h / -10 °C / Green chemistry 1.2: 2.17 h / -10 - 20 °C / Green chemistry 2.1: toluene-4-sulfonic acid; 1,3-dichloro-5,5-dimethylhydantoin / acetonitrile / 6 h / 25 °C / Green chemistry 3.1: potassium carbonate; water / chloroform / 20 h / Reflux; Green chemistry |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: copper(ll) bromide / chloroform; ethyl acetate 2: potassium carbonate / acetonitrile 3: hydrogenchloride / ethanol; ethyl acetate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: potassium carbonate / acetonitrile 2: hydrogenchloride / ethanol; ethyl acetate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With hydrogenchloride In ethanol; ethyl acetate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: bromine / chloroform / 1 h / 5 - 30 °C 2.1: potassium carbonate / chloroform / 18 h / Reflux 3.1: hydrogen / methanol; N,N-dimethyl-formamide / 1 h / 25 °C 4.1: pyridine / acetonitrile / 0 - 25 °C / Reflux 4.2: 0.5 h / 5 - 30 °C | ||
Multi-step reaction with 5 steps 1: hydrogen; palladium on activated charcoal / ethanol 2: triethylamine / dichloromethane 3: copper(ll) bromide / chloroform; ethyl acetate 4: potassium carbonate / acetonitrile 5: hydrogenchloride / ethanol; ethyl acetate | ||
Multi-step reaction with 4 steps 1.1: palladium 10% on activated carbon; ammonium formate; sodium sulfate / ethyl acetate / 2 h / Reflux; Green chemistry 2.1: iodine; phosphorous acid trimethyl ester; N-ethyl-N,N-diisopropylamine / chloroform / 0.17 h / -10 °C / Green chemistry 2.2: 2.17 h / -10 - 20 °C / Green chemistry 3.1: toluene-4-sulfonic acid; 1,3-dichloro-5,5-dimethylhydantoin / acetonitrile / 6 h / 25 °C / Green chemistry 4.1: potassium carbonate; water / chloroform / 20 h / Reflux; Green chemistry |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethyl [2]alcohol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: sulfuric acid / 1 h / 80 °C 1.2: 60 °C 2.1: ethyl [2]alcohol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With water; potassium carbonate In chloroform for 20h; Reflux; Green chemistry; | 7 Example 7 Synthesis of Conivaptan hydrochloride In a 500 mL three-necked flask, 39.7 g of compound 10 (0.08 mol), 3.8 g of acetamidine hydrochloride (0.04 mol),5.5 g of potassium carbonate (0.04 mol) and 0.54 g of distilled water (0.03 mol) were dissolved in 300 ml of chloroform. Reflux reaction 20h, TLC tracking and monitoring until the reaction was complete after the reaction was stopped, cooled to room temperature. Washed three times with (300 ml X 3) of distilled water, taken organic phase,Dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the crude product. The crude product was dissolved in ethanol, concentrated hydrochloric acid was added in an appropriate amount, and the solid was isolated by freezing. The mixture was suction filtered and dried in vacuo to give a solid. The solid was dissolved in water and extracted with dichloromethane (200 ml × 3). Concentrated and dried under reduced pressure to give 15.4 g The yield is 72%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: iodine; phosphorous acid trimethyl ester; pyridine / tetrahydrofuran / 0.17 h / -10 °C / Green chemistry 1.2: 2.17 h / -10 - 20 °C / Green chemistry 2.1: potassium hydroxide; potassium carbonate / water / 2 h / 50 °C / Cooling with ice; Green chemistry 3.1: polyphosphoric acid / 1,1,2,2-tetrachloroethane / 2 h / 120 °C / Green chemistry 4.1: palladium 10% on activated carbon; ammonium formate; sodium sulfate / ethyl acetate / 2 h / Reflux; Green chemistry 5.1: iodine; phosphorous acid trimethyl ester; N-ethyl-N,N-diisopropylamine / chloroform / 0.17 h / -10 °C / Green chemistry 5.2: 2.17 h / -10 - 20 °C / Green chemistry 6.1: toluene-4-sulfonic acid; 1,3-dichloro-5,5-dimethylhydantoin / acetonitrile / 6 h / 25 °C / Green chemistry 7.1: potassium carbonate; water / chloroform / 20 h / Reflux; Green chemistry |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: iodine; phosphorous acid trimethyl ester; pyridine / tetrahydrofuran / 0.17 h / -10 °C / Green chemistry 1.2: 2.17 h / -10 - 20 °C / Green chemistry 2.1: potassium hydroxide; potassium carbonate / water / 2 h / 50 °C / Cooling with ice; Green chemistry 3.1: polyphosphoric acid / 1,1,2,2-tetrachloroethane / 2 h / 120 °C / Green chemistry 4.1: palladium 10% on activated carbon; ammonium formate; sodium sulfate / ethyl acetate / 2 h / Reflux; Green chemistry 5.1: iodine; phosphorous acid trimethyl ester; N-ethyl-N,N-diisopropylamine / chloroform / 0.17 h / -10 °C / Green chemistry 5.2: 2.17 h / -10 - 20 °C / Green chemistry 6.1: toluene-4-sulfonic acid; 1,3-dichloro-5,5-dimethylhydantoin / acetonitrile / 6 h / 25 °C / Green chemistry 7.1: potassium carbonate; water / chloroform / 20 h / Reflux; Green chemistry |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1.1: potassium hydroxide; potassium carbonate / water / 2 h / 50 °C / Cooling with ice; Green chemistry 2.1: polyphosphoric acid / 1,1,2,2-tetrachloroethane / 2 h / 120 °C / Green chemistry 3.1: palladium 10% on activated carbon; ammonium formate; sodium sulfate / ethyl acetate / 2 h / Reflux; Green chemistry 4.1: iodine; phosphorous acid trimethyl ester; N-ethyl-N,N-diisopropylamine / chloroform / 0.17 h / -10 °C / Green chemistry 4.2: 2.17 h / -10 - 20 °C / Green chemistry 5.1: toluene-4-sulfonic acid; 1,3-dichloro-5,5-dimethylhydantoin / acetonitrile / 6 h / 25 °C / Green chemistry 6.1: potassium carbonate; water / chloroform / 20 h / Reflux; Green chemistry |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: polyphosphoric acid / 1,1,2,2-tetrachloroethane / 2 h / 120 °C / Green chemistry 2.1: palladium 10% on activated carbon; ammonium formate; sodium sulfate / ethyl acetate / 2 h / Reflux; Green chemistry 3.1: iodine; phosphorous acid trimethyl ester; N-ethyl-N,N-diisopropylamine / chloroform / 0.17 h / -10 °C / Green chemistry 3.2: 2.17 h / -10 - 20 °C / Green chemistry 4.1: toluene-4-sulfonic acid; 1,3-dichloro-5,5-dimethylhydantoin / acetonitrile / 6 h / 25 °C / Green chemistry 5.1: potassium carbonate; water / chloroform / 20 h / Reflux; Green chemistry |