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Structure of 1207557-35-4

Chemical Structure| 1207557-35-4

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Product Details of [ 1207557-35-4 ]

CAS No. :1207557-35-4
Formula : C11H11BrN2O3
M.W : 299.12
SMILES Code : O=C(C1=C2C(OC)=CC(Br)=CN2N=C1)OCC
MDL No. :MFCD17926418
InChI Key :SPTBJSZTWDNCHO-UHFFFAOYSA-N
Pubchem ID :58385978

Safety of [ 1207557-35-4 ]

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

Application In Synthesis of [ 1207557-35-4 ]

* 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 [ 1207557-35-4 ]

[ 1207557-35-4 ] Synthesis Path-Downstream   1~4

  • 2
  • [ 1207557-35-4 ]
  • [ 1207557-36-5 ]
YieldReaction ConditionsOperation in experiment
60% Step B: DecarboxylationA solution of ethyl 6-bromo-4-methoxylpyrazolo[l,5-a]pyridine-3-carboxylate (15, 5.2 g, 18.24 mmol) in HBr (100 ml, 884 mmol) was heated to 100 0C for 1 hour. After cooling to 0 0C, IM NaOH (182 ml, 912 mmol) was used to neutralize the solution. The reaction mixture was diluted in ethyl acetate, washed with saturated aqueous sodium hydroxide (IN) and brine then dried over Na2SO4. After filtration and concentration, the residue was purified by column chromatography (0-35% EtOAc in hexanes, linear gradient) to give 6-bromo-4- methoxypyrazolo[l,5-alpha]rhoyridine (16, 2.475 g, 10.90 mmol, 60 % yield). MS APCI: (M + H]+ m/z 228.1.; Scheme 2.Molecules of type 21 were prepared according to scheme 2. O- Mesitylenesulfonylhydroxylamine (1) was used to access W-imino-pyridinium mesitylenesulphonate 14. [3+2] Cyclization of 2 with ethyl propiolate yields pyrazolopyridine 15. Decarboxylation in neat hydrobromic acid afforded 16. Functional ization of the 6-position of the pyrazolopyridine core is accomplished via a Suzuki coupling reaction to install aryl or heteToaromatic functionality (17) using known or commercially available boronic acids or esters. For specific boronic ester examples, see WO 2004052286 A2 and WO 2007085873 Al . Halogenation via reaction with //-iodosuccinimide enables a second Suzuki coupling of iodide 18 with thiophcnc boronic ester to yield coupling product 19. Hydrolysis of the ester yielded acid 20 and subsequent coupling with an amine yielded target 21.
  • 3
  • [ 50720-12-2 ]
  • [ 1207557-35-4 ]
  • ethyl 4-bromo-6-methoxypyrazolo[1,5-a]pyridine-3-carboxylate [ No CAS ]
  • 4
  • 1-amino-3-bromo-5-methoxypyridin-1-ium 2,4,6-trimethylbenzene-1-sulfonate [ No CAS ]
  • [ 623-47-2 ]
  • [ 1207557-35-4 ]
  • ethyl 4-bromo-6-methoxypyrazolo[1,5-a]pyridine-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
21 g With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 48.0h; To a magnetically stirred white suspension of 1 -amino-3 -bromo-5 -methoxypyridin- 1 -ium 2,4,6-trimethylbenzenesulfonate (33.24 g, 82.42 mmol) in DMF (82 mL) at ambient temperature was added TEA (22.98 mL, 164.8 mmol), followed by drop-wise addition of ethyl propiolate (16.71 mL, 164.8 mmol). After vigorous stirring for 2 d, the reaction was slowly quenched via portion- wise addition to rapidly stirring ice water (820 mL). The mixture was stirred at ambient temperature for 10 mm and then vacuum filtered. Solids collected were rinsed with water and airdried, yielding the title compounds as an orange solid in an isomeric ratio of about 4:1 (by ?H NMR) with the 6-Br isomer as the major isomer (21 g). The wet solid isomeric mixture (about 75% w/w) was directly used in Step 3 without further purification. MS (apci) m/z = 298.9, 300.9 (M+H). Regioisomeric ratio was determined by MeO chemical shift in ?H NMR (CDC13) 3.98 (6-Br isomer) vs. 3.83 (4-Br isomer).
With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 48.0h; To a magnetically stirred white suspension of 1 -amino-3 -bromo-5 -methoxypyridin- 1 -ium 2,4,6- trimethylbenzenesulfonate (33.24 g, 82.42 mmol) in DMF (82 mL) at ambient temperature was added TEA (22.98 mL, 164.8 mmol), followed by dropwise addition of ethyl propiolate (16.71 mL, 164.8 mmol). After vigorous stirring for 2 d, the reaction was slowly quenched via portion- wise addition to rapidly stirring ice water (820 mL). The mixture was stirred at ambient temperature for 10 mm and then vacuum filtered. Solids collected were rinsed with water and air- dried, yielding the title compounds as an orange solid in an isomeric ratio of about 4:1 (by ?H NMR) with the 6-Br isomer as the major isomer (21 g). The wet solid isomeric mixture (about 75% w/w) was directly used in Step 3 without further purification. MS (apci) m/z = 298.9, 300.9 (M+H). Regioisomeric ratio was determined by MeO chemical shift in ?H NMR (CDC13) 3.98 (6-Br isomer) vs. 3.83 (4-Br isomer).
21 g With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 48.0h; Preparation of Ethyl 6-bromo-4-methoxypyrazolo|"l,5-a"|pyridine-3- carboxylate and Ethyl 4-bromo-6-methoxypyrazolo|"l,5-a"|pyridine-3-carboxylate. To a magnetically stirred white suspension of l-amino-3-bromo-5-methoxypyridin-l-ium 2,4,6- trimethylbenzenesulfonate (33.24 g, 82.42 mmol) in DMF (82 mL) at ambient temperature was added TEA (22.98 mL, 164.8 mmol), followed by drop-wise addition of ethyl propiolate (16.71 mL, 164.8 mmol). After vigorous stirring for 2 d, the reaction was slowly quenched via portion-wise addition to rapidly stirring ice water (820 mL). The mixture was stirred at ambient temperature for 10 min and then vacuum filtered. Solids collected were rinsed with water and air-dried, yielding the title compounds as an orange solid in an isomeric ratio of about 4: 1 (by MR) with the 6-Br isomer as the major isomer (21 g). The wet solid isomeric mixture (about 75% w/w) was directly used in Step 3 without further purification. MS (apci) m/z = 298.9, 300.9 (M+H). Regioisomeric ratio was determined by MeO chemical shift in 1H MR (CDCh) delta 3.98 (6-Br isomer) vs. 3.83 (4-Br isomer).
21 g With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 48.0h; To a magnetically stirred white suspension of1 -amino-3-bromo-5-methoxypyridin-1 -ium 2,4,6-trimethyl- benzenesulfonate (2a) (33.24 g, 82.42 mmol) in DMF (82 mL) at ambient temperature was added TEA (22.98 mL, 164.8 mmol), followed by drop-wise addition of ethyl propiolate (16.71 mL, 164.8 mmol). Afier vigorous stirring for 2 d, the reaction was slowly quenched via portion-wise addition to rapidly stirring ice water (820 mL). The mixture was stirred at ambient temperature for 10 mm and then vacuum filtered. Solids collected were rinsed with water and air-dried, yielding the title compounds as an orange solid in an isomeric ratio of about 4:1 (by ?H NMR) with compound 3a as the major isomer (21 g). The wet solid isomeric mixture (about 75% w/w) was directly used in the next step without further purification. MS (apci) mlz=298.9, 300.9 (M+H). Regioisomeric ratio was determined by MeO chemical shift in ?H NMR (CDC13) oe 3.98 (3a) vs. 3.83 (4a).
With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 48.0h; To a magnetically stirred white suspension of 1-amino-3-bromo-5-methoxypyridin-1-ium-2,4,6-trimethylbenzenesulfonate (33.24 g, 82.42 mmol) in DMF (82 mL) at ambient temperature was added TEA (22.98 mL, 164.8 mmol), followed by dropwise addition of ethyl propiolate (16.71 mL, 164.8 mmol). After vigorous stirring for 2 d, the reaction was slowly quenched via portion-wise addition to rapidly stirring ice water (820 mL). The mixture was stirred at ambient temperature for 10 min and then vacuum filtered. Solids collected were rinsed with water and air-dried, yielding the title compounds as an orange solid in an isomeric ratio of about 4:1 (by 1H NMR) with the 6-Br isomer as the major isomer (21 g). The wet solid isomeric mixture (about 75% w/w) was directly used in Step 3 without further purification. MS (apci) m/z = 298.9, 300.9 (M+H). Regioisomeric ratio was determined by MeO chemical shift in 1H NMR (CDCl3) delta 3.98 (6-Br isomer) vs.3.83 (4-Br isomer).
With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 48.0h; To a magnetically stirred white suspension of 1-amino-3-bromo-5-methoxypyridin-1-ium 2,4,6- trimethylbenzenesulfonate (33.24 g, 82.42 mmol) in DMF (82 mL) at ambient temperature was added TEA (22.98 mL, 164.8 mmol), followed by drop-wise addition of ethyl propiolate (16.71 mL, 164.8 mmol). After vigorous stirring for 2 d, the reaction was slowly quenched via portion- wise addition to rapidly stirring ice water (820 mL). The mixture was stirred at ambient temperature for 10 min and then vacuum filtered. Solids collected were rinsed with water and air- dried, yielding the title compounds as an orange solid in an isomeric ratio of about 4:1 (by 1H NMR) with the 6-Br isomer as the major isomer (21 g). The wet solid isomeric mixture (about 75% w/w) was directly used in Step 3 without further purification. MS (apci) m/z = 298.9, 300.9 (M+H). Regioisomeric ratio was determined by MeO chemical shift in 1H NMR (CDCl3) delta 3.98 (6-Br isomer) vs.3.83 (4-Br isomer).

 

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