Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | ||||||
{[ item.p_purity ]} | {[ item.pr_size ]} | Inquiry |
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price) ]} |
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate,item.pr_is_large_size_no_price) ]} | {[ item.pr_usastock ]} | in stock Inquiry - | {[ item.pr_chinastock ]} | {[ item.pr_remark ]} in stock Inquiry - | Login | Inquiry |
Please Login or Create an Account to: See VIP prices and availability
CAS No. : | 212141-54-3 | MDL No. : | MFCD08458963 |
Formula : | C20H15ClN4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | - |
M.W : | 346.81 | Pubchem ID : | - |
Synonyms : |
PTK787;ZK-222584;CGP-7978;PTK787/ZK 222584;CGP79787D;ZK-232934;CGP-797870;CGP-79787
|
Chemical Name : | N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | 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 |
---|---|---|
With phosphorus pentaoxide; conc. ammonia; triethylamine hydrochloride; In chloroform; water; | Example 4 1-(4-Chloroanilino)-4-(4-pyridylmethyl)phthalazine A mixture of 14.19 g (0.1 mol) phosphorus pentoxide, 13.77 g (0.1 mol) triethylamine hydrochloride and 12.76 g (0.1 mol) 4-chloroaniline is heated and stirred in a nitrogen atmosphere at 200 C. until a homogeneous melt has formed (about 20 min). To the melt, 5.93 g (0.025 mol) 4-(4-pyridylmethyl)-1(2H)-phthalazinone (for preparation see German Auslegeschrift no. 1 061 788 [published 23.07.1959]) is added, and the reaction mixture is stirred for 3 h at 2000 C. After the reaction mixture has cooled to about 100 C., 200 ml of water is added. Stirring is continued until the temperature reaches about 30 C., and then 20 ml conc. ammonia (30% aqueous ammonium hydroxide solution) and 900 ml chloroform are added consecutively. As soon as a diphasic mixture has formed, the organic phase is separated off, dried over anhydrous sodium sulfate, filtered, and the filtrate evaporated on a RE to a volume of about 50 ml, to which 100 ml acetate is then added, and the mixture is cooled in an ice bath. The crystallizate obtained is filtered off and washed with acetate and ether. After recrystallization from methanol and drying under HV for 8 h at 120 C., the title compound is obtained; m.p. 194-195 C.; ESI-MS: (M+H)+=347. | |
With phosphorus pentaoxide; conc. ammonia; triethylamine hydrochloride; In chloroform; water; | EXAMPLE 4 1-(4-Chloroanilino)-4-(4-pyridylmethyl)phthalazine A mixture of 14.19 g (0.1 mol) phosphorus pentoxide, 13.77 g (0.1 mol) triethylamine hydrochloride and 12.76 g (0.1 mol) 4-chloroaniline is heated and stirred in a nitrogen atmosphere at 200 C. until a homogeneous melt has formed (about 20 min). To the melt, 5.93 g (0.025 mol) 4-(4-pyridylmethyl)-1(2H)-phthalazinone (for preparation see German Auslegeschrift no. 1 061 788 [published 23.07.1959]) is added, and the reaction mixture is stirred for 3 h at 200 C. After the reaction mixture has cooled to about 100 C., 200 ml of water is added. Stirring is continued until the temperature reaches about 30 C., and then 20 ml conc. ammonia (30% aqueous ammonium hydroxide solution) and 900 ml chloroform are added consecutively. As soon as a diphasic mixture has formed, the organic phase is separated off, dried over anhydrous sodium sulfate, filtered, and the filtrate evaporated on a RE to a volume of about 50 ml, to which 100 ml acetate is then added, and the mixture is cooled in an ice bath. The crystallizate obtained is filtered off and washed with acetate and ether. After recrystallization from methanol and drying under HV for 8 h at 120 C., the title compound is obtained; m.p. 194-195 C.; ESI-MS: (M+H)+=347. | |
A mixture of 14.19 g (0.1 mol) phosphorus pentoxide, 13.77 g (0.1 mol) triethylamine hydrochloride and 12.76 g (0.1 mol) 4-chloroaniline is heated and stirred in a nitrogen atmosphere at 200 C. until a homogeneous melt has formed (about 20 min). To the melt, 5.93 g (0.025 mol) 4-(4-pyridylmethyl)-l (2H)- phthalazinone (for preparation see German Auslegeschrift no. 1 061 788 [published 23.07.1959]) is added, and the reaction mixture is stirred for 3 h at 200 C. After the reaction mixture has cooled to about 100 C, 200 ml of water is added. Stirring is continued until the temperature reaches about 30 C, and then 20 ml cone, ammonia (30% aqueous ammonium hydroxide solution) and 900 ml chloroform are added consecutively. As soon as a diphasic mixture has formed, the organic phase is separated off, dried over anhydrous sodium sulfate, filtered, and the filtrate evaporated on a RE to a volume of about 50 ml, to which 100 ml acetate is then added, and the mixture is cooled in an ice bath. The crystallizate obtained is filtered off and washed with acetate and ether. After recrystallization from methanol and drying under HV for 8 h at 120 C, the title compound is obtained; m.p. 194-195 C; ESI-MS: (M+H) + =347. |
Example 4 1-(4-Chloroanilino)-4-(4-pyridylmethyl)phthalazine A mixture of 14.19 g (0.1 mol) phosphorus pentoxide, 13.77 g (0.1 mol) triethylamine hydrochloride and 12.76 g (0.1 mol) 4-chloroaniline is heated and stirred in a nitrogen atmosphere at 200C until a homogeneous melt has formed (about 20 min). To the melt, 5.93 g (0.025 mol) 4-(4-pyridylmethyl)-1 (2H)-phthalazinone (for preparation see ]) is added, and the reaction mixture is stirred for 3 h at 200C. After the reaction mixture has cooled to about 100C, 200 ml of water is added. Stirring is continued until the temperature reaches about 30C, and then 20 ml conc. ammonia (30% aqueous ammonium hydroxide solution) and 900 ml chloroform are added consecutively. As soon as a diphasic mixture has formed, the organic phase is separated off, dried over anhydrous sodium sulfate, filtered, and the filtrate evaporated on a RE to a volume of about 50 ml, to which 100 ml acetate is then added, and the mixture is cooled in an ice bath. The crystallizate obtained is filtered off and washed with acetate and ether. After recrystallization from methanol and drying under HV for 8 h at 120C, the title compound is obtained; m.p. 194-195 C; ESI-MS: (M+H)+=347. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In butan-1-ol; at 100℃; for 0.5h;Product distribution / selectivity; | A mixture of 1.28 g (5 mmol) l-chloro-4-(4-pyridylmethyl)phthalazine, 0.67 g (5.25 mmol) 4-chloroaniline and 15 ml 1-butanol is heated for 0.5 h at 100 C while stirring in a nitrogen atmosphere. The mixture is then cooled to RT, filtered, and the filtrate washed with 1-butanol and ether. For purification, the crystallizate is dissolved in 40 ml of hot methanol, the solution treated with activated carbon, filtered via Hyflo Super CeI, and the filtrate evaporated to about half its original volume, resulting in the formation of a crystalline precipitate. After cooling to 0 C, filtration, washing of the filter residue with ether, and drying under HV for 8 h at 130 C, the title compound is obtained; m.p. >270 C; l H NMR (DMSO-d 6 ) 9.80-11.40 (br), 8.89-8.94 (m, IH), 8.67 (d, 2H)5 8.25-8.30 (m, IH), 8.06-8.17 (m, 2H), 7.87 (d, 2H), 7.69 (d, 2H)5 7. 49 (d, 2H), 4.81 (s, 2H); ESI-MS: (M+H) +=347. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; for 2h;Heating / reflux;Product distribution / selectivity; | A mixture of 0.972 g (3.8 mmol) l-chloro-4-(4- pyridylmethyl)phthalazine, 0.656 g (4 mmol) 4-chloroaniline hydrochloride (Research Organics, Inc., Cleveland, Ohio, USA) and 20 ml ethanol is heated for 2 h under reflux. The reaction mixture is cooled in an ice bath, filtered, and the crystallizate washed with a little ethanol and ether. After drying under HV for 8 h at 110 C. and for 10 h at 150 C, the title compound is obtained as a result of thermal removal of HCl; m.p. >270 C; ' H NMR (DMSO-d 6 ) 9.80-11.40 (br), 8.89-8.94 (m, IH), 8.67 (d, 2H), 8.25-8.30 (m, IH), 8.06-8.17 (m, 2H), 7.87 (d, 2H), 7. 69 (d, 2H), 7.49 (d, 2H), 4.81 (s, 2H); ESI-MS: (M+H) +=347. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; pyrographite; | Example 21 [4-(4-Chloranilino)phthalazin-1-yl](pyridin-4-yl)ketone Heating of a mixture of 1-(4-chloranilino)-4-(4-pyridylmethyl)-phthalazine (Example 4 in WO 98/35958) and charcoal in boiling methanol for about 7 days in an open vessel leads to partial oxidation of the methylen-bridge of 1-(4-chloranilino)-4-(4-pyridylmethyl)-phthalazine. After cooling to RT, unchanged 1-(4-chloranilino)-4-(4-pyridylmethyl)-phthalazine crystallizes out and can be filtered off. Chromatography (SiO2; dichloromethane/methanol 98:2) of the concentrated filtrate then leads to [4-(4-chloranilino)phthalazin-1-yl](pyridin-4-yl)ketone and rac. [4-(4-chloranilino)phthalazin-1-yl](pyridin-4-yl)methanol (see Expl. 78 in WO 98/35958). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid; In tetrahydrofuran; ethanol; dichloromethane; ethyl acetate; toluene; | Example 25 rac. 1-(4-Chlor-anilino)-4-(pyridin-4-yl-fluormethyl)-phthalazine Under N2-atmosphere, 7.02 ml (4.65 mmol; 15% in toluene) of potassium bis(trimethylsilyl)-amide are dissolved in 78 ml THF and then cooled to -78 C. A solution of 537.5 mg (1.55 mmol) of 1-(4-chlor-anilino)-4-(pyridin-4-yl-methyl)-phthalazine (see WO 98/35958) in 30 ml THF is added dropwise. The resulting black solution is stirred for additional 30 min, then 1.00 g (4.65 mmol) of 2-fluoro-3,3-dimethyl-2,3-dihydro-1,2-benzisothiazole (Fluka; Buchs, Switzerland) in 30 ml THF are added slowly. The reaction solution slowly turns to yellow-orange. After 3 h at -78 C., a solution of 1 ml acetic acid in 5 ml of THF is added. The reaction mixture is poured into a diluted NaHCO3-solution and extracted three times with ethyl acetate. The organic layers are washed with 2 portions of water and brine, dried (Na2SO4) and concentrated. Chromatography (SiO2; EtOAc/dichloromethane 2:1 to EtOAc to EtOAc/EtOH 9:1 to 4:1) and crystallization from acetonitrile/acetone finally gave the title compound: 1H NMR (DMSO-d6) δ9.50 (s, HN), 8.65 (d, 1H), 8.61 (d, 2H), 8.16 (d, 1H), 8.03 (t, 1H), 7.99 (t, 1H), 7.96 (d, 2H), 7.43 (d, 2H), 7.40 (d, 2H), 7.34 (s, 1H); 19F NMR (DMSO-d6) δ-50.7; FAB-MS (M+H)+=365. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 4 1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine A mixture of 14.19 g (0.1 mol) phosphorus pentoxide, 13.77 g (0.1 mol) triethylamine hydrochloride and 12.76 g (0.1 mol) 4-chloroaniline is heated and stirred in a nitrogen atmosphere at 200 C. until a homogeneous melt has formed (about 20 minutes). To the melt, 5.93 g (0.025 mol) 4-(4-pyridylmethyl)-1 (2H)-phthalazinone (for preparation see German Auslegeschrift No. 1 061 788 [published 23.07.1959]) is added, and the reaction mixture is stirred for 3 hours at 200 C. After the reaction mixture has cooled to about 100 C., 200 mL of water is added. Stirring is continued until the temperature reaches about 30 C., and then 20 mL conc. ammonia (30% aqueous ammonium hydroxide solution) and 900 mL chloroform are added consecutively. As soon as a diphasic mixture has formed, the organic phase is separated off, dried over anhydrous sodium sulfate, filtered and the filtrate evaporated on a RE to a volume of about 50 mL, to which 100 mL acetate is then added, and the mixture is cooled in an ice bath. The crystallizate obtained is filtered off and washed with acetate and ether. After re-crystallization from methanol and drying under HV for 8 hours at 120 C., the title compound is obtained; m.p. 194-195 C.; ESI-MS: (M+H)+=347. | ||
, wherein said compound is selected from the group consisting of: 1-(4-Methylanilino)-4-(4-pyridylmethyl)phthalazine; 1-(4-Chloroanilino)-4-(4-pyridylmethyl)phthalazine; 1-Anilino-4-(4-pyridylmethyl)phthalazine; 1-Benzylamino-4-(4-pyridylmethyl)phthalazine; 1-(4-Methoxyanilino)-4-(4-pyridylmethyl)phthalazine; 1-(3-Benzyloxyanilino)-4-(4-pyridylmethyl)phthalazine; 1-(3-Methoxyanilino)-4-(4-pyridylmethyl)phthalazine; 1-(2-Methoxyanilino)-4-(4-pyridylmethyl)phthalazine; 1-(4-Trifluoromethylanilino)-4-(4-pyridylmethyl)phthalazine; ... | ||
High preference is given to a compound selected from the group consisting of: 1-(4-Chloroanilino)-4-(4-pyridylmethyl)phthalazine; 1-(3-Chloroanilino)-4-(4-pyridylmethyl)phthalazine; 1-Anilino-4-(4-pyridylmethyl)phthalazine; 1-Benzylamino-4-(4-pyridylmethyl)phthalazine; 1-(4-Methoxyanilino)-4-(4-pyridylmethyl)phthalazine; ... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.8% | With potassium carbonate; In N,N-dimethyl-formamide; at 110 - 115℃; for 5h; | Add 100 g of DMF to a 250 ml four-necked flask equipped with a stirring, thermometer, and reflux condenser.11.8 g (0.05 mol) of 1-amino-4-(pyridin-4-yl)methylpyridazine (IV),15.0 g (0.08 mol) of 4-bromochlorobenzene, 10.0 g of potassium carbonate, and the reaction was stirred at 110 to 115 C for 5 hours.After cooling to 20 to 25 C, the reaction liquid was poured into 200 g of water, filtered, and the filter cake was washed successively with 30 g of water and 20 g of isopropyl alcohol, and dried.The yield of 16.1 g of vatalanib was 92.8%, and the liquid phase purity was 99.6%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.4% | With potassium carbonate; In N,N-dimethyl-formamide; at 100 - 105℃; for 5h; | To a 250 ml four-necked flask equipped with a stirring, thermometer, and reflux condenser.Add 100 grams of DMF, 11.8 grams (0.05 moles) of 1-amino-4-(pyridin-4-yl)methylpyridazine (IV),14.5 g (0.06 mol) of 4-iodochlorobenzene, 10.0 g of potassium carbonate, and stirred at 100 to 105 C for 5 hours.Cool to 20 to 25 C and pour the reaction liquid into 200 g of water.After filtration, the filter cake was washed successively with 30 g of water and 20 g of isopropyl alcohol, and dried.The yield of 16.2 g of vatalanib was 93.4%, and the liquid phase purity was 99.7%. |