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Chemical Structure| 178308-61-7 Chemical Structure| 178308-61-7

Structure of 178308-61-7

Chemical Structure| 178308-61-7

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Product Details of [ 178308-61-7 ]

CAS No. :178308-61-7
Formula : C9H3Cl2N3
M.W : 224.05
SMILES Code : N#CC1=CC2=C(C(Cl)=NN=C2Cl)C=C1
MDL No. :MFCD06797633
InChI Key :FRJDQOMCKHDEJQ-UHFFFAOYSA-N
Pubchem ID :10656738

Safety of [ 178308-61-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of [ 178308-61-7 ]

* 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.

  • Downstream synthetic route of [ 178308-61-7 ]

[ 178308-61-7 ] Synthesis Path-Downstream   1~19

  • 1
  • [ 2620-50-0 ]
  • [ 178308-61-7 ]
  • 1-[(Benzo[1,3]dioxol-5-ylmethyl)-amino]-4-chloro-phthalazine-6-carbonitrile [ No CAS ]
  • [ 178309-46-1 ]
  • 2
  • [ 2393-23-9 ]
  • [ 178308-61-7 ]
  • 1-chloro-6-cyano-4-(4-methoxybenzyl)aminophthalazine [ No CAS ]
  • 4-Chloro-1-(4-methoxy-benzylamino)-phthalazine-6-carbonitrile [ No CAS ]
  • 3
  • [ 178308-61-7 ]
  • 1-(3-Chloro-4-methoxy-phenyl)-ethylamine; hydrochloride [ No CAS ]
  • 1-chloro-4-(α-methyl-3-chloro-4-methoxybenzyl)amino-6-cyanophthalazine [ No CAS ]
  • 4-Chloro-1-[1-(3-chloro-4-methoxy-phenyl)-ethylamino]-phthalazine-6-carbonitrile [ No CAS ]
  • 4
  • [ 178308-61-7 ]
  • [ 41965-95-1 ]
  • [ 178308-63-9 ]
  • 4-Chloro-1-(3-chloro-4-methoxybenzyl)amino-6-cyanophthalazine [ No CAS ]
  • 5
  • [ 178308-61-7 ]
  • 3-Chloro-4-ethoxy-benzylamine; hydrochloride [ No CAS ]
  • 1-chloro-4-(3-chloro-4-ethoxybenzyl)amino-6-cyano-phthalazine [ No CAS ]
  • 4-chloro-1-(3-chloro-4-ethoxybenzyl)amino-6-cyano-phthalazine [ No CAS ]
  • 6
  • [ 178309-35-8 ]
  • [ 178308-61-7 ]
  • 7
  • [ 178309-36-9 ]
  • [ 178308-61-7 ]
YieldReaction ConditionsOperation in experiment
70% With thionyl chloride; trichlorophosphate; In dichloromethane; Preparative Example 6 6-Cyano-1,4-dichlorophthalazine STR21 6-Carbamoyl-2,3-dihydro-1,4-phthalazinedione (1.00 g, 0.0049 mol) was suspended in a mixture comprising 20 ml of phosphorus oxychloride and 20 ml of thionyl chloride. The obtained suspension was heated under reflux one whole day and night and distilled in a vacuum to remove the solvent. The obtained residue was dissolved in methylene chloride, followed by washing with water. The organic phase was dried over anhydrous magnesium sulfate and purified by silica gel column chromatography to give 0.76 g of the title compound as a light brown crystal (yield: 70%).
  • 8
  • [ 3676-85-5 ]
  • [ 178308-61-7 ]
  • 9
  • [ 34613-09-7 ]
  • [ 178308-61-7 ]
  • 10
  • [ 21343-93-1 ]
  • [ 178308-61-7 ]
  • 11
  • [ 1204-28-0 ]
  • [ 178308-61-7 ]
  • 12
  • [ 169045-13-0 ]
  • [ 178308-61-7 ]
  • [ 240400-76-4 ]
YieldReaction ConditionsOperation in experiment
1,8-diazabicyclo[5.4.0]undec-7-ene; In 1-methyl-pyrrolidin-2-one; 1,4-Dichlorophthalazine-6-carbonitrile and 3-cyano-4-methoxybenzylamine were stirred at room temperature in 1-methyl-2-pyrrolidinone in the presence of DBU, whereby 1-chloro-4-[(3-cyano-4-methoxybenzyl)amino]-6-phthalazine carbonitrile was obtained as a less polar product. 1H-NMR (400 MHz, DMSO-d6) δ; 3.87 (3H, s), 4.70 (2H, d, J=5.6 Hz), 7.20 (1H, d, J=8.4 Hz), 7.70 (1H, dd, J=2.4, 8.4 Hz), 7.75 (1H, d, J=2.4 Hz), 8.19 (1H, d, J=8.4 Hz), 8.34 (1H, dd, J=1.2, 8.4 Hz), 8.48 (1H, t, J=5.6 Hz), 8.97 (1H, s).
  • 13
  • [ 240400-81-1 ]
  • [ 178308-61-7 ]
  • 1-Chloro-4-[(3-ethyl-4-methoxybenzyl)amino]-6-phthalazinecarbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
1,8-diazabicyclo[5.4.0]undec-7-ene; In 1-methyl-pyrrolidin-2-one; 1,4-Dichlorophthalazine-6-carbonitrile and 3-ethyl-4-methoxybenzylamine hydrochloride were stirred at room temperature in 1-methyl-2-pyrrolidinone in the presence of DBU, whereby 1-chloro-4-[(3-ethyl-4-methoxybenzyl)amino]-6-phthalazine carbonitrile was obtained as a less polar compound. 1H-NMR (400 MHz, CDCl3) δ; 1.14 (3H, t, J=7.5 Hz), 2.60 (2H, q, J=7.5 Hz), 3.81 (3H, s), 4.84 (2H, s), 6.80 (1H, d, J=8.2 Hz), 7.25 (1H, d, J=2.0 Hz), 7.30 (1H, dd, J=2.0, 8.2 Hz), 8.06 (1H, d, J=9.0 Hz), 8.27 (1H, d, J=9.0 Hz), 8.42 (1H, m).
  • 14
  • [ 67952-93-6 ]
  • [ 178308-61-7 ]
  • 1-Chloro-4-[(3-chloro-4-methylbenzyl)amino]-6-phthalazinecarbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
1,8-diazabicyclo[5.4.0]undec-7-ene; In 1-methyl-pyrrolidin-2-one; 1,4-Dichlorophthalazine-6-carbonitrile and 3-chloro-4-methylbenzylamine were stirred at room temperature in 1-methyl-2-pyrrolidinone in the presence of DBU, whereby the title compound was obtained as a less polar compound. 1H-NMR (400 MHz, DMSO-d6) δ; 2.29 (3H, s), 4.73 (2H, d, J=5.2 Hz), 7.28-7.32 (2H, m), 7.45 (1H, d, J=0.8 Hz), 8.20 (1H, dd, J=8.4, 0.4 Hz), 8.34 (1H, d, J=8.4, 1.6 Hz), 8.52 (1H, t, J=5.2 Hz), 9.00 (1H, m).
YieldReaction ConditionsOperation in experiment
Example 1 1-Chloro-4-(3-chloro-4-methoxybenzyl)amino-6-cyanophthalazine STR28 6-Cyano-1,4-dichlorophthalazine (66.2 g) prepared in Preparative Example 3 and 3-chloro-4-methoxybenzylamine (92 g) were suspended in 1200 ml of tetrahydrofuran, followed by the addition of 250 ml of triethylamine. The obtained mixture was heated under reflux for 6 hours. The crystals thus precipitated were filtered out and the filtrate was concentrated in a vacuum. The residue was purified by silica gel column chromatography ›solvent: toluene/tetrahydrofuran (10:[1)] to recover a less polar product. The title compound (59 g) was obtained as a pale-yellow crystal. M.p.: 213.0-214.5 C.; MASS: 359 (MH+); 1H-NMR (400 MHz, CDCl3) δ: 3.87(3H, s), 4.78(2H, d, J=5.0 Hz), 5.75(1H, t, J=5.0 Hz), 6.87(1H, d, J=8.5 Hz), 7.31(1H, dd, J=8.5, 2.0 Hz), 7.43(1H, d, J=2.0 Hz), 8.05(1H, dd, J=8.5, 1.5 Hz), 8.24(1H, dd, J=1.5, 1.0Hz), 8.29(1H, dd, J=8.5, 0.5 Hz)
  • 16
  • [ 7087-68-5 ]
  • [ 178309-35-8 ]
  • [ 178308-61-7 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; sodium hydrogencarbonate; In dichloromethane; trichlorophosphate; Preparative Example 3 6-Cyano-1,4-dichlorophthalazine STR18 6-Cyano-2,3-dihydro-1,4-phthalazinedione (69 g) was suspended in 400 ml of phosphorus oxychloride, followed by the addition of 75 ml of diisopropyl-ethylamine. The obtained mixture was heated under reflux for 40 minutes. Excess phosphorus oxychloride was distilled away in a vacuum and the residue was dissolved in methylene chloride. The obtained solution was poured onto ice/water. The resulting mixture was filtered through Celite to remove insolubles and the Celite was washed weith methylene chloride. The filtrates were together extracted with methylene chloride and the organic phase was washed with a saturated aqueous solution of sodium hydrogencarbonate, dilute hydrochloric acid and a saturated aqueous solution of common salt, dried over anhydrous magnesium sulfate and filtered through silica gel. The filtrate was distilled in a vacuum to remove the solvent. The title compound (66 g) was obtained as a palely yellowish-orange solid. 1H-NMR (400 MHz, CDCl3) δ: 8.24(1H, dd, J=8.5, 1.5 Hz), 8.47(1H, dd, J=8.5, 1.0 Hz), 8.68(1H, dd, J=1.5, 1.0 Hz)
YieldReaction ConditionsOperation in experiment
4-(3-Chloro-4-methoxybenzyl)amino-6-cyano-1-(4-hydroxypiperidino)phthalazine Hydrochloride 69 g of 6-cyano-2,3-dihydro-1,4-phthaladinedione was suspended in 400 ml of phosphorus oxychloride. After adding 75 ml of diisopropylethylamine, the mixture was heated under reflux for 40 minutes. Then the excessive phosphorus oxychloride was evaporated and the residue was dissolved in methylene chloride and poured into ice water. After filtering off the unnecessary through celite, the celite filter was washed with methylene chloride. The filtrate was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate, dilute hydrochloric acid and brine and dried over anhydrous magnesium sulfate. This solution was filtered by using silica gel and the solvent was evaporated to give 66 g of 6-cyano-1,4-dichlorophthalazine as a pale orange solid. 1H-NMR(400 MHz, CDCl3) δ: 8.24(1H, dd, J=8.5, 1.5 Hz), 8.47(1H, dd, J=8.5, 1.0 Hz), 8.68(1H, dd, J=1.5, 1.0 Hz).
  • 18
  • [ 115514-77-7 ]
  • [ 178308-61-7 ]
  • [ 178308-63-9 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In tetrahydrofuran; 66.2 g of <strong>[178308-61-7]6-cyano-1,4-dichlorophthalazine</strong> and 92 g of 3-chloro-4-methoxybenzylamine were suspended in 1,200 ml of tetrahydrofuran. After adding 250 ml of triethylamine, the resulting mixture was heated under reflux for 6 hours. The resulting crystals were filtered off and the filtrate was evaporated. The residue was purified by silica gel column chromatography (toluene:tetrahydrofuran=10:1) to give 59 g of 1-chloro-4-(3-chloro-4-methoxybenzyl)amino-6-cyanophthalazine as pale yellow crystals. M.p.: 213.0-214.5 C., Mass 359(MH+), 1H-NMR(400 MHz, CDCl3) δ: 3.87(3H, s), 4.78(2H, d, J=5.0 Hz), 5.75(1H, t, J=5.0 Hz), 6.87(1H, d, J=8.5 Hz), 7.31(1H, dd, J=8.5, 2.0 Hz), 7.43(1H, d, J=2.0 Hz), 8.05(1H, dd, J=8.5, 1.5 Hz), 8.24(1H, dd, J=1.5, 1.0 Hz), 8.29(1H, dd, J=8.5, 0.5 Hz).
  • 19
  • [ 178308-61-7 ]
  • [ 357263-39-9 ]
  • [ 1095639-29-4 ]
  • [ 1095639-27-2 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 100.0℃; for 4.5h; EXAMPLE 29Preparation of (R)-(4-(4-chloro-7-cyanophthalazin-1-yl)-3-methylpiperazin-1-yl)(phenyl)methanone (JK-25A) and (R)-(4-(4-chloro-6-cyanophthalazin-1-yl)-3-methylpiperazin-1-yl)(phenyl)methanone (JK-25B) <strong>[178308-61-7]1,4-dichloro-6-cyanophthalazine</strong> (1.38 g, 6.16 mmol) and (R)-(3-methylpiperazin-1-yl)(phenyl)methanone (1.38 g, 6.78 mmol) were dissolved/suspended in N,N-diisopropylethylamine (2.15 mL) and NMP (3 mL), fitted with an argon balloon and heated at 100 C. for 4.5 hours. The reaction was taken up in ethyl acetate (80 mL) and washed with aqueous K2CO3 (10%), water, and saturated sodium chloride. The organics were dried (MgSO4) and evaporated to give a brown oil. Chromatography over silica gel with a gradient of hexanes/0-70% ethyl acetate gave two products. Product JK-25A was a yellow solid 1.14 g; product JK-25B was 392 mg of a yellow solid. Both compounds had MS (M+H)+=385.1.
 

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