Structure of 1677-80-1
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CAS No. : | 1677-80-1 |
Formula : | C4H2Cl2N2 |
M.W : | 148.98 |
SMILES Code : | ClC1=CC=NN=C1Cl |
MDL No. : | MFCD20040517 |
InChI Key : | JADVVTZXHQUFLS-UHFFFAOYSA-N |
Pubchem ID : | 252150 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
* 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 |
---|---|---|
92% | With sodium hydroxide; In water; at 100℃; for 15.0h; | Example 26A 3-chloro-6-phenoxypyridazine 3,4-Dichloropyridazine (Aldrich, 4.47 g, 30 mmol) in NaOH (10%, 20 mL) was treated with phenol (Aldrich, 1.88 g, 20 mmol) at 100 C. for 15 hours. After cooling to room temperature, the mixture extracted with ethyl acetate (2*50 mL). The extracts were combined and concentrated under reduced pressure. The title compound was purified by chromatography (SiO2, Hexanes:ethyl acetate=80:20, Rf. 0.5) as a solid (3.8 g, yield, 92%). 1H NMR (CDCl3, 300 MHz) δ 7.11-7.29 (m, 3H), 7.38-7.55 (m, 4H) ppm. MS (DCl/NH3) m/z 207 (M+H)+, 209 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
101 mg | With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 50℃; for 12.0h; | A mixture of 3-amino-5-chloropyrazine-2-thiol (100 mg, 0.545 mmol), 3,4- dicholoropyridazine (81 mg, 0.545 mmol), and DIPEA (0.142 mL, 0.817 mmol) in MeCN (5.5 mL) was stirred for 12 h at 50 C. After cooling to RT, the precipitate was collected by vacuum filtration to give 6-chloro-3-((3-chloropyridazin-4-yl)thio)pyrazin-2-amine (101 mg, 0.368 mmol) as a brown solid. NMR (400 MHz, DMSO-< ) δ ppm 8.90 (d, J=5.4 Hz, 1 H), 7.95 (s, 1 H), 7.31 (s, 2 H), 7.15 (d, J=5.3 Hz, 1 H). MS m/z 274.1 (M+H)+. |
101 mg | With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 50℃; for 12.0h; | A mixture of 3-amino-5-chloropyrazine-2-thiol(100 mg, 0.545 mmol), 3,4-dicholoropyridazine (81 mg,0.545 mmol), and DIPEA (0.142 mL, 0.8 17 mmol) in MeCN(5.5 mL) was stirred for 12 h at 500 C. After cooling to RT,the precipitate was collected by vacuum filtration to give6-chioro-3-((3-chloropyridazin-4-yl)thio)pyrazin-2-amine(101 mg, 0.368 mmol) as a brown solid. ‘H NMR (400MHz, DMSO-d5) ö ppm 8.90 (d, J=5.4 Hz, 1H), 7.95 (s, 1H),7.31 (s, 2H), 7.15 (d, J=5.3 Hz, 1H). MS mlz 274.1 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With trichlorophosphate; In acetonitrile; at 80℃; for 3.0h; | Compound 3 (25 g, 0.19 mol) was added to acetonitrile (200 ml)Then, phosphorus oxychloride (73 g, 0.48 mol) was added and the reaction was refluxed at 80 C for 3 hours. After the TLC reaction was complete,After the reaction solution was cooled to room temperature, the reaction solution was poured directly into ice water (200 ml)Add sodium bicarbonate to weakly alkaline (PH about 7-8),And extracted twice with ethyl acetate (300 ml). The organic phases were combined,The organic phase was washed with saturated brine (400 ml), dried over anhydrous sodium sulfate,Concentrate the organic phase. The resulting crude product was purified by column chromatography,Compound 4 (18.0 g, 0.12 mol) was obtained. Yield of about 64%. |
With trichlorophosphate; In acetonitrile; for 1.0h;Reflux; | Put 3-hydroxy-4-chloropyridazine in a three-necked flask equipped with a reflux and drying tube device(3.00g, 23mmol), phosphorus oxychloride (10.58g, 69mmol), acetonitrile (20ml),Warm up to reflux with stirring, keep for 1 hour to react, cool to room temperature, pour under stirring80ml ice water, adjust the pH to 7-8 with sodium bicarbonate, extract twice with dichloromethane (50ml×2),Saturated brine (50ml), dried over anhydrous sodium sulfate, evaporated under reduced pressure at room temperature to 1/3 of the solution,Stop distillation and add20ml N,N-dimethylacetamide, continue to distill until the solution does not decrease, set aside. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 80℃; for 16.0h;Inert atmosphere; | Under nitrogen atmosphere, to a 100 mL single-necked flask were sequentially added the crude product of sodium ((R)-1-((R)-1,1-dimethylethylsulfinamido)-8-azaspiro[4.5]decan-8-yl)imidazo[1,2-c]pyrimidin-8-thiolate (50 mg, 0.12 mmol), <strong>[1677-80-1]3,4-dichloropyridazine</strong> (19 mg, 0.13 mmol) and acetonitrile (3 mL), followed by DIPEA (31 mg, 0.24 mmol), and the reaction solution was heated to 80 C. and stirred for 16 hours. After the reaction solution was cooled, the residue obtained by concentration under reduced pressure was purified by silica gel chromatography (ethyl acetate/methanol with a gradient of 0 to 30%) to obtain (R)-N-((R)-8-(8-((3-chloropyridazin-4-yl)thio)imidazo[1,2-c]pyrimidin-5-yl)-8-azaspiro[4.5]decan-1-yl)-2-methylpropane-2-sulfinamide (10 mg, yield: 16%). LCMS: m/z 520.2 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Put in a three-necked bottle equipped with nitrogen protection device6-trifluoromethylindole (3.70g, 20mmol), 40ml of N,N-dimethylacetamide, stir and reduce the temperature to below 0,Add 60% sodium hydrogen (0.88g, 22mmol) in batches, keep warm and stir for 0.5 hours,Then add the filtrate of step one dropwise, after the addition, the temperature will rise naturally, and the reaction will be stirred overnight.Add 50ml water, extract three times with ethyl acetate (100ml×3), combine the organic phases,Wash with brine, dry with anhydrous sodium sulfate, and concentrate to dryness under reduced pressure.The concentrate is purified by silica gel chromatography,1-(3-Trichloro-pyridazin-4-yl)-6-trifluoromethyl-1H-indole (Intermediate 1-a) is obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; at 10℃; for 0.5h; | In a three-necked bottle equipped with a reflux and drying tube device,Put in 3-hydroxy-4-chloropyridazine (12.00g, 92mmol),Phosphorus oxychloride (42.32g, 276mmol), acetonitrile (60ml), heated to reflux with stirring, kept the reaction for 1 hour, cooled to room temperature,Pour into 300ml ice water with stirring, adjust the pH to 7-8 with sodium bicarbonate,Extract twice with dichloromethane (150ml×2), saturated brine (100ml), dry with anhydrous sodium sulfate, evaporate to one third of the solution under reduced pressure at room temperature, stop distillation,Stir and cool to below 10, add triethylamine(23.27g, 230mmol), then slowly dropwise add methyl thioglycolate (10.74g, 101mmol),After the addition, keep for 0.5 hour, add 2N hydrochloric acid, adjust the pH to 5-6, stir and separate the layers, and then extract the water layer with 150ml dichloromethane once, combine the organic phases,Wash with brine, evaporate to dryness under reduced pressure, add 50ml ethyl acetate and stir to crystallize.Filter, dry, and collect the solid (3-chloropyridazine-4-mercapto) methyl acetate(Intermediate 29-a). |