Category: 1120-95-2

Brief introduction of 1120-95-2

1120-95-2, The synthetic route of 1120-95-2 has been constantly updated, and we look forward to future research findings.

1120-95-2, 3-Chloropyridazine is a pyridazine compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

[00578] To a solution of tert-butyl (1-((1r,4r)-4-hydroxycyclohexyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)(methyl)carbamate (0.0207 g, 0.0485 mmol) in N,N-dimethylformamide (0.48 mL) was added sodium hydride (0.00140 g, 0.0582 mmol). After 5 mins, 3-chloropyridazine (0.0111 g, 0.0971 mmol) was added and heated to 95 C overnight. The reaction mixture was partitioned between ethyl acetate (10 mL) and water (10 mL), extracted with ethyl acetate (2x5mL), washed with water (5 mL) and brine (5 mL), dried over Na2SO4, filtered and concentrated. The crude oil was resuspended in dichloromethane (5 mL) and TFA (5 mL) was added. After 1 hour, the reaction mixture was concentrated in vacuo and the resultant oil was resuspended in 1 mL of a solution of 60:40 ACN:water with 2% TFA modifier. The product was purified by HPLC (5-95% ACN in water with 0.2% TFA modifier). The product containing fractions were partitioned between DCM and aqueous NaHCO3, dried over sodium sulfate, filtered and concentrated to obtain N-methyl-3-(1-methyl-1H-pyrazol-4-yl)-1-((1r,4r)-4-(pyridazin-3-yloxy)cyclohexyl)-1H-pyrazolo[4,3-c]pyridin-6-amine (0.0105 g, 0.0260 mmol, 53.5 % yield) as a white solid. Mass spectrum (apci) m/z = 405.2 (M+H). 1H NMR (CDCl3) delta 8.83 (m, 1H), 8.699(s, 1H), 7.98 (s, 1H), 7.87 (s, 1H), 7.37 (dd, J = 9.0, 4.5 Hz, 1H), 6.95 (dd, J = 9.0, 1.2 Hz, 1H), 6.04 (s, 1H), 5.49 (tt, J = 11.0, 4.3 Hz, 1H), 4.87 (br s, 1H), 4.35 (tt, J = 11.7, 4.1 Hz, 1H), 4.00 (s, 3H), 2.98 (d, J = 5.1 Hz, 3H), 2.51 (m, 2H), 2.35 (m, 2H), 2.15 (m, 2H), 1.75 (m, 2H).

1120-95-2, The synthetic route of 1120-95-2 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; ARRAY BIOPHARMA INC.; ALLEN, Shelley; BOYS, Mark Laurence; COOK, Adam; GAUDINO, John; HINKLIN, Ronald Jay; LAIRD, Ellen; MCNULTY, Oren T.; METCALF, Andrew T.; NEWHOUSE, Brad; ROBINSON, John E.; (545 pag.)WO2019/113190; (2019); A1;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem

 

Downstream synthetic route of 1120-95-2

1120-95-2, As the paragraph descriping shows that 1120-95-2 is playing an increasingly important role.

1120-95-2, 3-Chloropyridazine is a pyridazine compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Ethyl (cis)-2-oxo-1-oxa-3-azaspiro[4.5]decane-8-carboxylate and ethyl (trans)-2-oxo-1-oxa-3-azaspiro[4.5]decane-8-carboxylate mixture (85/15 mixture) (obtained from combination of four different batches prepared in a similar fashion to preparation of Intermediates 2 and 3, procedures a and b, 10 g, 44.0 mmol), K3PO4 (28.0 g, 132 mmol), copper(I) iodide (0.838 g, 4.40 mmol), 3-chloropyridazine (prepared according to WO/0107416, 6.05 g, 52.8 mmol) were collected into a 250 ml reaction flask, deareated, and then suspended in 1,4-dioxane (150 ml) under nitrogen. Trans-1,2-diaminocyclohexane (1.058 ml, 8.80 mmol) was added to the resulting mixture. The reaction was then warmed up to reflux (ext temp. 130 C., int temp 105 C.). The reaction mixture was stirred at that temperature for overall 24 hours. The reaction mixture was taken up with DCM (1000 ml) and poured into water (300 ml) containing 10 ml of ammonium hydroxide, and left under stirring for 10 min. Then, the resulting organic phase was washed with water (2¡Á100 ml) and brine (2¡Á100 ml), dried over Na2SO4, filtered and then concentrated. The resulting crude was purified with Biotage SP1, over 65i silica column, using cyclohexane and EtOAc as eluent to afford two different batches of the title compound.Batch 1: Ethyl (trans)-2-oxo-3-(3-pyridazinyl)-1-oxa-3-azaspiro[4.5]decane-8-carboxylate (3.4 g) was isolated as a single isomer, colourless solid, contaminated by ca 30% of starting chloropyridazine. This batch left at room temperature, in the light, after some days, resulted in a strongly dark coloured and degradated residue.Batch 2: A 80/20 mixture of trans/cis isomers was isolated as a colourless solid (2.2 g) and repurified on Biotage SP1, with a Biotage 65i silica column, using cyclohexane and ethyl acetate as eluent to give isomerically pure ethyl (trans)-2-oxo-3-(3-pyridazinyl)-1-oxa-3-azaspiro[4.5]decane-8-carboxylate (1.6 g)1H NMR (400 MHz, CDCl3): delta 8.96 (dd, 1H), 8.56 (dd, 1H), 7.50 (dd, 1H), 4.20 (s, 2H), 4.18 (q, 2H), 2.51 (quint, 1H), 2.17-1.75 (m, 8H), 1.29 (t, 3H); UPLC-MS: 0.60 min, 306 [M+H]+.From these two purifications two batches of cis isomer were also isolated:Batch 1: ethyl (cis)-2-oxo-3-(3-pyridazinyl)-1-oxa-3-azaspiro[4.5]decane-8-carboxylate as single isomer and colourless solid (4.7 g)Batch 2: ethyl (cis)-2-oxo-3-(3-pyridazinyl)-1-oxa-3-azaspiro[4.5]decane-8-carboxylate (0.5 g).1H NMR (400 MHz, CDCl3): delta 8.96 (dd, 1H), 8.57 (dd, 1H), 7.50 (dd, 1H), 4.18 (q, 3H), 4.14 (s, 2H), 2.51 (quint, 1H), 2.46-2.37 (m, 1H), 2.21-1.66 (m, 8H), 1.29 (t, 3H); UPLC-MS: 1.04 min, 306 [M+H]+.

1120-95-2, As the paragraph descriping shows that 1120-95-2 is playing an increasingly important role.

Reference£º
Patent; Biagetti, Matteo; Contini, Stefania Anna; Genski, Thorsten; Guery, Sebastien; Leslie, Colin Philip; Mazzali, Angelica; Pizzi, Domenica Antonia; Sabbatini, Fabio Maria; Seri, Catia; US2009/203705; (2009); A1;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem

 

Simple exploration of 1120-95-2

The synthetic route of 1120-95-2 has been constantly updated, and we look forward to future research findings.

1120-95-2, 3-Chloropyridazine is a pyridazine compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 4-4 (Trans)-8-({[6-(2-methylphenyl)-3-pyridazinyl]amino}methyl)-3-(3-pyridazinyl)-1-oxa-3-azaspiro[4.5]decan-2-one dihydrochloride (Trans)-8-({[6-(2-methylphenyl)-3-pyridazinyl]amino}methyl)-1-oxa-3-azaspiro[4.5]decan-2-one (Intermediate 45, 40.0 mg, 0.114 mmol), 3-chloropyridazine (prepared according to WO/0107416, 13 mg, 0.114 mmol), copper(I) iodide (21.62 mg, 0.114 mmol), trans-1,2-diaminocyclohexane (0.027 ml, 0.227 mmol), K3PO4 (72.3 mg, 0.341 mmol) were collected in a closed vial and suspended in 1,4-dioxane (4 ml). The resulting mixture was stirred at 130 C. for 4 hours. Solvent was removed under vacuum. The crude was taken up with DCM (8 ml) and filtered over a separating tube. The resulting solution was purified with Biotage SP1, over a 12M NH2 Varian cartridge, eluding with a gradient of cyclohexane and ethyl acetate. The title compound was eluted with EtOAc and recovered as colourless oil. Then it was further purified with Biotage SP1, over a 12M NH2 Varian cartridge, eluding with a gradient of cyclohexane and ethyl acetate to recover the title compound as nearly chemically pure colourless oil (30 mg). 1H NMR (400 MHz, CDCl3): delta 8.97 (dd, 1H), 8.58 (dd, 1H), 7.52 (dd, 1H), 7.45-7.41 (m, 1H), 7.36-7.29 (m, 4H), 6.75 (m, 1H), 4.92 (brs, 2H), 3.45 (t, 2H), 2.43 (s, 3H), 2.15-1.11 (m, 9H)., 1120-95-2

The synthetic route of 1120-95-2 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Biagetti, Matteo; Contini, Stefania Anna; Genski, Thorsten; Guery, Sebastien; Leslie, Colin Philip; Mazzali, Angelica; Pizzi, Domenica Antonia; Sabbatini, Fabio Maria; Seri, Catia; US2009/203705; (2009); A1;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem

 

Brief introduction of 1120-95-2

The synthetic route of 1120-95-2 has been constantly updated, and we look forward to future research findings.

1120-95-2, 3-Chloropyridazine is a pyridazine compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

General procedure: To a suspension of NaH (1.1 mmol) in anhydrous DMF, cooled at 0 C, a solution of the appropriate aryl chloride (1.0 mmol) and of the appropriate glycidol (1.0 mmol) in the same solvent was added dropwise. The reaction mixture was stirred at room temperature overnight, quenched with H2O and extracted with AcOEt (3 ¡Á 20 mL). The organic layers were collected, dried over Na2SO4 and concentrated under reduced pressure. The crude was purified on a silica gel column (CHCl3/AcOEt, 9:1 as eluent) to give pure compound as an oil., 1120-95-2

The synthetic route of 1120-95-2 has been constantly updated, and we look forward to future research findings.

Reference£º
Article; Hansen, Hanne D.; Lacivita, Enza; Di Pilato, Pantaleo; Herth, Matthias M.; Lehel, Szabolcs; Ettrup, Anders; Andersen, Valdemar L.; Dyssegaard, Agnete; De Giorgio, Paola; Perrone, Roberto; Berardi, Francesco; Colabufo, Nicola Antonio; Niso, Mauro; Knudsen, Gitte M.; Leopoldo, Marcello; European Journal of Medicinal Chemistry; vol. 79; (2014); p. 152 – 163;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem

 

Some tips on 1120-95-2

The synthetic route of 1120-95-2 has been constantly updated, and we look forward to future research findings.

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1120-95-2,3-Chloropyridazine,as a common compound, the synthetic route is as follows.

Example 143; 5-[(1R)-1-methyl-2-morpholin-4-yl-2-oxoethoxy]-N [3-methyl-4-(pyridazin-3- yloxy)phenyl] quinazolin-4-amine; Starting aniline: 3-methyl-4-(pyridazin-3-yloxy)aniline. Yield: 89 mg; 56% on a 0.33 mmol scale. NMR Spectrum: (400 MHz) 1.58 (d, 3H), 2.13 (s, 3H), 3.8-3.3 (m, 8H), 5.88 (q, 1H), 7.17 (d, 1H), 7.30 (d, 1H), 7.36 (d, 1H), 7.47 (d, 1H), 7.75 (m, 2H), 7.90 (dd, 1H), 8.00 (d, 1H), 8.53 (s, 1H), 8.99 (m, 1H), 11.09 (s, 1H); Mass spectrum: MH+ 487; The 3-methyl-4-(pyridazin-3-yloxy)aniline used as starting material was prepared as follows: A mixture of 4-amino-2-methylphenol (550 mg, 4.47 mmol), 3-chloropyridazine (510 mg, 4.47 mmol; Libermann et al., Bull. Soc. Chem. Fr., 1962, 1735), potassium carbonate (926 mg, 6.71 mmol) in DMA (10 ml) was irradiated in a Personal Chemistry EMRYSNo. Optimizer EXP microwave synthesisor at 180 C for 50 minutes. After cooling, the mixture was partitioned with water and dichloromethane. After filtration of the insoluble, the organic layer was washed with water and brine and dried over magnesium sulfate. After evaporation of the solvents, the residue was purified by chromatography on silica gel (eluant: ethyl acetate) to give 3-methyl-4- (pyridazin-3-yloxy)aniline a brown solid (638 mg, 71%) ; Mass spectrum: MH+ 202., 1120-95-2

The synthetic route of 1120-95-2 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2005/118572; (2005); A1;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem

 

Simple exploration of 1120-95-2

The synthetic route of 1120-95-2 has been constantly updated, and we look forward to future research findings.

1120-95-2, 3-Chloropyridazine is a pyridazine compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

The boronate ester (19 g, crude) from Step F above, 3-chloro- pyridazine (4.8 g, 42 mmol), and cesium carbonate (21 g, 63 mmol) were suspended in DMF (120 mL) and water (30 mL). The mixture was purged with argon. 1,1′- Bis(diphenylphosphino)ferrocenedichloropalladium (240 mg, 0.33 mmol) was added to the mixture. The mixture was heated at 1000C for 2 hours. After cooling to room temperature, the reaction mixture was diluted with dichloromethane, and filtered through a pad of Celite. The filtrate was washed with water, brine, dried over sodium sulfate and concentrated. The residue was purified by flash chromatography (98:1.8:0.2 to 95:4.5:0.5 dichloromethane/methanol/concentrated ammonium hydroxide) to give 5-(tert-butyldimethylsilyloxy)-2-methyl-8-(pyridazin-3-yl)-2, 3,4,5- tetrahydro-lH-benzo[c]azepine (4.7 g, 40% for 2 steps) as an oil. This oil was resolved using Chiralcel OD column (eluente :80 etaep:20 IPA:0.1 DEA) to give (+)- enantiomer (2.3 g, 98%, ([alpha]25D, +26.9 (C, 0.29 Methanol) and (-)-enantiomer (2.3 g, 98%, [alpha]25D, -23.2 (C, 0.28 Methanol)): 1H NMR (CDCl3, 300 MHz) delta 9.15 (d, J= 4.8 Hz, IH), 7.91-7.84 (m, 3H), 7.54-7.50 (m, 2H), 4.96 (t, J= 5.2 Hz, IH), 4.26-4.05 (m, IH), 3.85-3.73 (m, IH), 3.30-3.21 (m, IH), 2.97-2.91 (m, IH), 2.32 (s, 3H) 1.95- 1.85 (m, 2H), 0.91 (s, 9H), 0.097-0.085 (m, 6H); ESI MS m/z 370 [M+H]+.The boronate ester (5.5 g, crude) from Step F above, 3-chloro- pyridazine (2.0 g, ~16 mmol), and cesium carbonate (4.2 g, 13 mmol) were suspended in DMF (30 mL) and water (8 mL). The mixture was purged with argon. 1,1′- Bis(diphenylphosphino)ferrocenedichloropalladium (400 mg, 0.52 mmol) was added to the mixture. The mixture was heated at 1000C for 2 hours. After cooling to room temperature, the reaction mixture was diluted with dichloromethane, and filtered through a pad of celite. The filtrate was washed with water, brine, dried over sodium sulfate and concentrated. The residue was purified by flash chromatography (98:1.8:0.2 to 95:4.5:0.5 dichloromethane/methanol/concentrated ammonium hydroxide) to give 5-(tert-butyldimethylsilyloxy)-2-methyl-8-(pyridazin-3-yl)-2, 3,4,5- tetrahydro-lH-benzo[c]azepine (1.3 g, 55% for 2 steps) as an brown oil: 1H NMR (CDCl3, 300 MHz) delta 9.15 (d, J= 4.8 Hz, IH), 7.91-7.84 (m, 3H), 7.54-7.50 (m, 2H), 4.96 (t, J= 5.2 Hz, IH), 4.20-4.10 (m, IH), 3.85-3.73 (m, IH), 2.97-2.91 (m, IH), 2.32 (s, 3H) d, J= 7.9 Hz, IH), 7.24 (d, J= 7.9 Hz, IH ), 4.82 (t, J= 4.9 Hz, IH), 3.64-3.61 (m, IH), 3.27-3.18 (m IH), 2.36 (s, 3H), 1.95-1.85 (m, 2H), 1.80-1.63 (m, 2H), 0.91 (s, 9H), 0.097-0.085 (m, 6H); ESI MS m/z 370 [M+H]+., 1120-95-2

The synthetic route of 1120-95-2 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; AMR TECHNOLOGY, INC.; BRISTOL-MYERS SQUIBB COMPANY; WO2008/141082; (2008); A1;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem

 

Brief introduction of 1120-95-2

The synthetic route of 1120-95-2 has been constantly updated, and we look forward to future research findings.

1120-95-2, 3-Chloropyridazine is a pyridazine compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,1120-95-2

INTERMEDIATE 306,6-Dimethyl-2-[6-(pyrida2in-3-yloxy)-2,3-dihvdro-4H-l,4-benzoxazin-4-yl]-6,7- dihvdro[ 1 ,3]thiazolor5,4-clpyridin-4(5H)-oneA mixture of Intermediate 17 (53 mg, 0.16 mmol), cesium carbonate (105 mg,0.32 mmol) and 3,6-dichloropyridazine (24 mg, 0.16 mmol) in NMP (2 mL) was heated to 1100C for 12 h. After cooling to r.t. it was concentrated in vacuo. Purification by preparative etaPLC (Method 5) gave the title compound (15 mg, 23%) as an off-white solid. deltaeta (CDCl3) 8.94 (IH, dd, J4.5, 1.3 Hz), 8.02 (IH, d, J2.4 Hz), 7.49 (IH, dd, J8.9,4.5 Hz), 7.19 (IH, dd, J 8.9, 1.3 Hz), 6.89-7.03 (2H, m), 5.21 (IH, s), 4.31-4.39 (2H, m),4.09-4.18 (2H, m), 2.86 (2H, s), 1.37 (6H, s).

The synthetic route of 1120-95-2 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; UCB PHARMA S.A.; WO2009/71895; (2009); A1;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem

 

Some tips on 1120-95-2

#N/A

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1120-95-2,3-Chloropyridazine,as a common compound, the synthetic route is as follows.

(i?)-2-Methyl-l-{3-[4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)- phenoxy]propyl} -pyrrolidine (1.1 g, 3.2 mmol), 3-chloropyridazine (0.485 g, 4.24 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.258 g, 0.223 mmol), K2CO3 (1.19 g, 8.6 mmol) in 1,2-dimethoxyethane (25 mL) and water (11.5 mL) were combined and degassed with argon. The reaction was heated at 85 0C for 15 h, cooled to rt, filtered through celite, taken up in CH2Cl2 (30 mL) and washed with water and saturated NaHCO3 solution. The CH2Cl2 layer was dried (Na2SO4) and evaporated. The product was purified by ISCO chromatography on silica gel, eluting with 5-15% MeOH/ DCM / 0.5% NH4OH. The HCl salt was prepared MeOH – ether-HCl to give a white solid, m.p. 198-201 0C; LCMS m/z = 298 (M + 1).

#N/A

Reference£º
Patent; CEPHALON, INC.; WO2009/97306; (2009); A1;,
Pyridazine – Wikipedia
Pyridazine | C4H4N2 – PubChem