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Chemical Structure| 1101121-05-4 Chemical Structure| 1101121-05-4

Structure of 1101121-05-4

Chemical Structure| 1101121-05-4

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Product Details of [ 1101121-05-4 ]

CAS No. :1101121-05-4
Formula : C8H5BrN2O2
M.W : 241.04
SMILES Code : O=C(C1=C2C=C(Br)C=CN2N=C1)O
English Name :5-Bromopyrazolo[1,5-a]pyridine-3-carboxylic acid
MDL No. :MFCD18837595
InChI Key :KPAHXGSXTRKJCE-UHFFFAOYSA-N
Pubchem ID :68507303

Safety of [ 1101121-05-4 ]

Application In Synthesis of [ 1101121-05-4 ]

* 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 [ 1101121-05-4 ]

[ 1101121-05-4 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 1101121-05-4 ]
  • [ 79-19-6 ]
  • [ 1101121-07-6 ]
YieldReaction ConditionsOperation in experiment
98% Stage #1: 5-bromopyrazolo[1,5-a]pyridine-3-carboxylic acid With thionyl chloride for 1h; Heating / reflux; Stage #2: thiosemicarbazide With pyridine In dichloromethane at 0℃; for 1.08333h; Stage #3: With sodium hydroxide; sulfuric acid; water more than 3 stages; 93.93.2 Step 93.2: 5 (X = Br) (100 mg, 0.41 mmol) was refluxed in SOCI2 (3 ml.) for 1h. The solvent was removed in vacuo. The residue was taken up in CH2CI2 (2 ml_) and added dropwise to a solution of thiosemicarbazide (38 mg, 0.42 mmol) in pyridine (5 mL) at 0 0C over 5 mins. After 1h, the solvents were removed in vacuo. The residue was taken up in concentrated H2SO4 (3 mL) and heated to 50 0C for 1 h. Ice was added to the solution, and then it was basified to pH 6 with 6M aqueous NaOH and stood for 1 h. The precipitate was filtered off, washed with water and dried to leave 5-(5-bromopyrazolo[1 ,5-a]pyridin-3- yl)-1 ,3,4-thiadiazol-2-amine (81: X = Br) as a pale yellow solid (120 mg, 98%). 1H NMR δ (400 MHz, d6-DMSO) 8.77 (dd, J 7.3, 0.7 Hz, 1H), 8.42 (s, 1 H), 8.32 (dd, J 2.2, 0.7 Hz, 1 H), 7.25 (br s, 2H), 7.22 (dd, J 7.3, 2.2 Hz, 1 H). LCMS (APCI+) 296 (MH+ with 79Br, 95%), 298 (MH+ with 81Br, 100%).
  • 2
  • [ 885276-93-7 ]
  • [ 1101121-05-4 ]
YieldReaction ConditionsOperation in experiment
92% With sodium hydroxide In ethanol; water at 75℃; for 6h; 5-Bromopyrazolo [1,5-a]pyridine-3-carboxylic acid (9e). Intermediate12 (1.00 g, 3.75 mmol) was dissolved in EtOH/H2O (5/1, 20 mL). Then 15 mL 1 M NaOH solution was added and the reaction mixture washeated to 75 C for 6 h. Then the solvent was removed under vacuumand basified to pH 1 with 1 M HCl solution with added dropwise toobtain compound 9e as a white solid without further purification. Yield:92 %. 1H NMR (400 MHz, DMSO-d6) 8.82 (d, J = 7.3 Hz, 1H), 8.42 (s,1H), 8.20 (d, J = 1.9 Hz, 1H), 7.29 (dd, J = 7.3, 2.2 Hz, 1H).
Stage #1: ethyl 5-bromopyrazolo[1,5-a]pyridine-3-carboxylate With water; potassium hydroxide In ethanol for 3h; Reflux; Stage #2: With hydrogenchloride In ethanol; water at 20℃; Synthesis of 5-bromo-N, N-bis(4-methoxybenzyl)pyrazolo[ 1 , 5-a]pyridine-3-carboxamide-26)1-25 1-26[000270] To a suspensions of ethyl 5-bromopyrazolo[1 ,5-a]pyridine-3-carboxylate (0.27 g, 1 .0 mmol) in EtOH (5 ml_) was added 6 N KOH (0.3 uL, 2.0 mmol). The reaction was heated to reflux for 3 hours then cooled to room temperature and neutralized to pH 6 with 1 M HCI. The resulting solid was filtered and dried under vacuum to yield 5-bromopyrazolo[1 ,5-a]pyridine-3-carboxylic acid (I-25) as a white solid. 1 H NMR (400MHz, DMSO-c/6) δ 8.83 (d, J = 7.6 Hz, 1 H), 8.42 (s, 1 H), 8.21 (d, J = 2.4 Hz, 1 H), 7.30 (dd, J = 2.0, 7.6 Hz, 1 H). MS m/z 240.9, 242.9 (M+1 )+.
99.36 % With sodium hydroxide In ethanol; water at 60 - 70℃; 7 Example 7: Preparation of compound SM8A In a 2L glass reaction bottle, add SM7A (200g, 743.23mmol) and ethanol (1200mL) in sequence, stir at room temperature; slowly add NaOH (44.59g, 1.11mol, dissolved in 400mL water), turn on heating; keep the internal temperature at 60~70°C Stir for 1 to 2 hours. When the SM7A content is detected by high-performance liquid chromatography-mass spectrometry to be less than 1%, stop heating. Cool the reaction solution to 0 to 10°C, slowly add dilute hydrochloric acid (preparation method: slowly add 100 mL of concentrated hydrochloric acid to 2400 mL of water), adjust the pH to 1 to 2, and continue stirring for 0.5 to 1 hour. Filter and pump dry; wash the filter cake twice with water slurry (600 mL × 2), pump dry, collect the filter cake, and blast dry it at 55°C for 36 hours to obtain 178g of off-white solid with a yield of 99.36%.
With water; lithium hydroxide In ethanol at 30℃; Inert atmosphere; 47.3 5-bromopyrazole[1,5-a]pyridine-3-carboxylic acid Add ethyl 5-bromopyrazole [1,5-a]pyridine-3-carboxylic acid (500mg, 1.85mmol), lithium hydroxide (450mg, 18.6mmol), ethanol (10mL) and water (2mL) to the three-necked flask in sequence. )After reacting at 30°C for 12 hours, the system appeared black. LC-MS was consistent with the target compound.Adjust pH=5~6, then extract with ethyl acetate, concentrate to dryness, and concentrate the filtrate to dryness.A crude product of 5-bromopyrazole[1,5-a]pyridine-3-carboxylic acid (500 mg) was obtained.
With water; lithium hydroxide In ethanol at 30℃; Inert atmosphere; 47.3 5-bromopyrazole[1,5-a]pyridine-3-carboxylic acid Add ethyl 5-bromopyrazole [1,5-a]pyridine-3-carboxylic acid (500mg, 1.85mmol), lithium hydroxide (450mg, 18.6mmol), ethanol (10mL) and water (2mL) to the three-necked flask in sequence. )After reacting at 30°C for 12 hours, the system appeared black. LC-MS was consistent with the target compound.Adjust pH=5~6, then extract with ethyl acetate, concentrate to dryness, and concentrate the filtrate to dryness.A crude product of 5-bromopyrazole[1,5-a]pyridine-3-carboxylic acid (500 mg) was obtained.
3.1 g With lithium hydroxide monohydrate; water In tetrahydrofuran; methanol at 50℃; Inert atmosphere; 1.5 Compound 1e (4.1 g, 15.2 mmol) was added to 50 mL of methanol, 10 mL of tetrahydrofuran, and 10 mL of water. Then, lithium hydroxide monohydrate (3.2 g, 76 mmol) was added in portions. The mixture was heated to 50 °C and stirred overnight. After the reaction was complete as monitored by TLC, the mixture was concentrated by rotary evaporation, and the pH was adjusted to 4 with 1 mol/L hydrochloric acid solution. The mixture was filtered, the filter cake was washed with water, and dried to obtain compound 1f (3.1 g, gray solid).

  • 3
  • [ 1101121-05-4 ]
  • [ 1394839-49-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: N,N-diethyl-N-isopropylamine; HATU / N,N-dimethyl-formamide / 0.5 h / 20 °C 1.2: 12 h / 20 °C 2.1: caesium carbonate / palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene / 1,4-dioxane / 0.5 h / 140 °C / Inert atmosphere; Microwave
  • 4
  • [ 1101121-05-4 ]
  • [ 1394838-11-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: N,N-diethyl-N-isopropylamine; HATU / N,N-dimethyl-formamide / 0.5 h / 20 °C 1.2: 12 h / 20 °C 2.1: caesium carbonate / palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene / 1,4-dioxane / 0.5 h / 140 °C / Inert atmosphere; Microwave 3.1: trifluoroacetic acid / dichloromethane / 12 h / 50 °C
  • 5
  • [ 1101121-05-4 ]
  • [ 1394838-26-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: N,N-diethyl-N-isopropylamine; HATU / N,N-dimethyl-formamide / 0.5 h / 20 °C 1.2: 12 h / 20 °C 2.1: caesium carbonate / palladium diacetate; ruphos / <i>tert</i>-butyl alcohol / 120 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 2 h / 20 °C 4.1: dimethyl sulfoxide / 3 h / 90 °C 5.1: trifluoroacetic acid / 2 h / 60 °C
  • 6
  • [ 1101121-05-4 ]
  • [ 1394839-53-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: N,N-diethyl-N-isopropylamine; HATU / N,N-dimethyl-formamide / 0.5 h / 20 °C 1.2: 12 h / 20 °C 2.1: caesium carbonate / palladium diacetate; ruphos / <i>tert</i>-butyl alcohol / 120 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 2 h / 20 °C 4.1: dimethyl sulfoxide / 3 h / 90 °C 5.1: sodium hydroxide; water; dihydrogen peroxide / methanol / 2 h / 0 - 20 °C
  • 7
  • [ 1101121-05-4 ]
  • [ 17061-62-0 ]
  • [ 1394838-84-6 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 5-bromopyrazolo[1,5-a]pyridine-3-carboxylic acid With N,N-diethyl-N-isopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: N,N-bis(p-methoxybenzyl)amine In N,N-dimethyl-formamide at 20℃; for 12h; [000271 ] To a solution of 5-bromopyrazolo[1 ,5-a]pyridine-3-carboxylic acid (I-25) (66 mg, 0.27 mmol) in DMF (3 ml_) was added DIEA (0.14 ml_) and HATU (0.10 g, 0.27 mmol). The reaction was stirred for 30 minutes at room temperature then bis(4- methoxybenzyl)amine (70 mg, 0.27 mmol) was added. Stirring was continued at room temperature for 12 hours. The reaction was diluted with EtOAc, washed with brine, dried over magnesium sulfate, filtered and reduced to dryness. The crude product was purified by flash column chromatography on silica with hexanes/EtOAc gradient as eluant to yield 5-bromo-N, N-bis(4-methoxybenzyl)pyrazolo[1 ,5-a]pyridine-3- carboxamide (I-26). 1 H NMR (400MHz, CDCI3) δ 8.50 (d, J = 2.4 Hz, 1 H), 8.26 (dd, J = 0.4, 7.2 Hz, 1 H), 7.88 (s, 1 H), 7.22 (d, J = 8.0 Hz, 4 H), 7.00 (dd, J = 2.0, 7.2 Hz, 1 H), 6.91 (d, J = 8.4 Hz, 4 H), 4.67 (s, 4 H), 3.82 (s, 6 H). MS m/z 480.1 , 482.1 (M+1 )+.
  • 8
  • [ 1101121-05-4 ]
  • [ 2766124-25-6 ]
YieldReaction ConditionsOperation in experiment
0.885 g With ammonium chloride; N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 2h; 10.1 Step 1: Synthesis of 5-bromopyrazolo[1,5-a]pyridine-3-carboxamide (Compound 169-2) 5-Bromopyrazolo[1,5-a]pyridine-3-carboxylic acid (1 g, 4.15 mmol), ammonium chloride (444 mg, 8.30 mmol), HATU (1.66 g, 4.36 mmol), DIPEA (1.61 g, 12.45 mmol) was dissolved in DMF (10 mL) and reacted at room temperature for 2 h. The reaction was added dropwise to water (100 mL), a solid was precipitated, filtered, and the filter cake was collected. to get the title compound, 0.885g
94.39 % With ammonium chloride; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 10 - 30℃; 8 Example 8: Preparation of compound SM9A In a 500mL glass reaction bottle, add SM8A (10g, 41.49mmol), dimethylformamide (60mL), EDCI (11.93g, 62.23mmol), HOBT (8.41g, 62.23mmol) and ammonium chloride (4.44g, 82.97mmol), start stirring. Slowly add diisopropylethylamine (16.09g, 124.46mmol) dropwise, maintaining the internal temperature at 10-30°C during the dropping process; after the dripping is completed, continue stirring for 22 hours. The SM8A content in the reaction solution is detected by HPLC to be <1%. Stop reacting. Slowly add purified water (300 mL) to the reaction solution. After the addition is completed, continue stirring for 1 to 2 hours. Filter, pump dry, wash the filter cake once with 5% sodium carbonate aqueous solution (100 mL) and purified water (100 mL), and pump dry; collect the filter cake and blast dry it at 50-55°C to constant weight (~21 h) to obtain 9.4 g off-white solid, yield 94.39%, HPLC purity of SM9A is 99.35%.
30.1 % With ammonium chloride; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 30℃; Inert atmosphere; 47.4 5-bromopyrazole[1,5-a]pyridin-3-amide Add 5-bromopyrazole[1,5-a]pyridine-3-carboxylic acid (500mg, 2.07mmol) to the three-necked flask.2-(7-Azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (1.25g, 3.29mmol), N,N-diisopropylethylamine (6.21mmol,1.08mL),Ammonium chloride (554mg, 10.4mmol) and N,N dimethylformamide (10mL),Then the reaction was heated at 30°C for 3 hours, and the reaction liquid turned yellow. LC-MS was consistent with the target compound, and the reaction was quenched by saturated ammonium chloride. Extract with 100ml methylene chloride,After spin drying under vacuum, purify using column chromatography (silica, petroleum ether/ethyl acetate = 50%).5-bromopyrazole[1,5-a]pyridin-3-amide (150 mg) was obtained, yield: 30.1%.
30.1 % With ammonium chloride; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 30℃; Inert atmosphere; 47.4 5-bromopyrazole[1,5-a]pyridin-3-amide Add 5-bromopyrazole[1,5-a]pyridine-3-carboxylic acid (500mg, 2.07mmol) to the three-necked flask.2-(7-Azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (1.25g, 3.29mmol), N,N-diisopropylethylamine (6.21mmol,1.08mL),Ammonium chloride (554mg, 10.4mmol) and N,N dimethylformamide (10mL),Then the reaction was heated at 30°C for 3 hours, and the reaction liquid turned yellow. LC-MS was consistent with the target compound, and the reaction was quenched by saturated ammonium chloride. Extract with 100ml methylene chloride,After spin drying under vacuum, purify using column chromatography (silica, petroleum ether/ethyl acetate = 50%).5-bromopyrazole[1,5-a]pyridin-3-amide (150 mg) was obtained, yield: 30.1%.

  • 9
  • [ 109-01-3 ]
  • [ 1101121-05-4 ]
  • [ 2922911-01-9 ]
YieldReaction ConditionsOperation in experiment
83.3 % Stage #1: 5-bromopyrazolo[1,5-a]pyridine-3-carboxylic acid With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; Stage #2: 1-methyl-piperazine In N,N-dimethyl-formamide at 20℃; Step 1 A mixture of 5-bromopyrazolo[1,5-a]pyridine-3-carboxylic acid (LXVI) (Commercially available from Advanced ChemBlocks Inc.) (300 mg, 1.24 mmol), DIPEA (0.44 mL, 2.53 mmol), and HATU (0.47 g, 1.24 mmol) in DMF (4 mL) was stirred at room temperature for 5 min. Then, 1-methylpiperazine (LXVII) (0.28 mL, 2.52 mmol) was added and the reaction mixture was continued at room temperature for 5 h. The solvents were concentrated in vacuo, the residue taken into EtOAc, washed with water, saturated aqueous NaHCO3, water, and brine. The organic layers were dried over anhydrous Na2SO4, then concentrated and under high vacuo to obtain crude (5-bromopyrazolo[1,5-a]pyridin-3-yl)(4-methylpiperazin-1-yl)methanone (LXVIII) (335 mg, 1.037 mmol, 83.3% yield) as a brown gummy solid, which was used in the next step without purification. ESIMS found for C13H15BrN4O m/z 323.0 (79BrM+H).
83.3 % Stage #1: 5-bromopyrazolo[1,5-a]pyridine-3-carboxylic acid With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; Stage #2: 1-methyl-piperazine In N,N-dimethyl-formamide at 20℃; Step 1 A mixture of 5 -bromopyrazolo[l, 5 -a]pyridine-3 -carboxylic acid (CXIX) (commercially available from Advanced ChemBlocks Inc.) (300 mg, 1.24 mmol), DIPEA (0.44 mb, 2.53 mmol), and HATU (0.47 g, 1.24 mmol) in DMF (4 mL) was stirred at room temperature for 5 min. Then, 1 -methylpiperazine (CXX) (0.28 mL, 2.52 mmol) was added and the reaction mixture was continued at room temperature for 5 h. The solvents were concentrated in vacuo, the residue taken into EtOAc, washed with water, saturated aqueous NaHCCh. water, and brine. The organic layers were dried over anhydrous Na2SC>4, then concentrated and under high vacuo to obtain crude (5-bromopyrazolo[l,5-a]pyridin-3-yl)(4-methylpiperazin-l-yl)methanone (CXXI) (335 mg, 1.037 mmol, 83.3% yield) as a brown gummy solid, which was used in the next step without purification. ESIMS found for CnH EBrN-iO m/z 323.0 (79BrM+H).
83.3 % Stage #1: 5-bromopyrazolo[1,5-a]pyridine-3-carboxylic acid With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; Stage #2: 1-methyl-piperazine In N,N-dimethyl-formamide at 20℃; Step 1 A mixture of 5-bromopyrazolo[1,5-a]pyridine-3-carboxylic acid (LXVI) (Commercially available from Advanced ChemBlocks Inc.) (300 mg, 1.24 mmol), DIPEA (0.44 mL, 2.53 mmol), and HATU (0.47 g, 1.24 mmol) in DMF (4 mL) was stirred at room temperature for 5 min. Then, 1-methylpiperazine (LXVII) (0.28 mL, 2.52 mmol) was added and the reaction mixture was continued at room temperature for 5 h. The solvents were concentrated in vacuo, the residue taken into EtOAc, washed with water, saturated aqueous NaHCO3, water, and brine. The organic layers were dried over anhydrous Na2SO4, then concentrated and under high vacuo to obtain crude (5-bromopyrazolo[1,5-a]pyridin-3-yl)(4-methylpiperazin-1-yl)methanone (LXVIII) (335 mg, 1.037 mmol, 83.3% yield) as a brown gummy solid, which was used in the next step without purification. ESIMS found for C13H15BrN4O m/z 323.0 (79BrM+H).
83.3 % Stage #1: 5-bromopyrazolo[1,5-a]pyridine-3-carboxylic acid With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; Stage #2: 1-methyl-piperazine In N,N-dimethyl-formamide at 20℃; Step 1 A mixture of 5 -bromopyrazolo[l, 5 -a]pyridine-3 -carboxylic acid (CXIX) (commercially available from Advanced ChemBlocks Inc.) (300 mg, 1.24 mmol), DIPEA (0.44 mb, 2.53 mmol), and HATU (0.47 g, 1.24 mmol) in DMF (4 mL) was stirred at room temperature for 5 min. Then, 1 -methylpiperazine (CXX) (0.28 mL, 2.52 mmol) was added and the reaction mixture was continued at room temperature for 5 h. The solvents were concentrated in vacuo, the residue taken into EtOAc, washed with water, saturated aqueous NaHCCh. water, and brine. The organic layers were dried over anhydrous Na2SC>4, then concentrated and under high vacuo to obtain crude (5-bromopyrazolo[l,5-a]pyridin-3-yl)(4-methylpiperazin-l-yl)methanone (CXXI) (335 mg, 1.037 mmol, 83.3% yield) as a brown gummy solid, which was used in the next step without purification. ESIMS found for CnH EBrN-iO m/z 323.0 (79BrM+H).

  • 10
  • [ 1101121-05-4 ]
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
80 % With tris(2,2-bipyridine)ruthenium(II) hexafluorophosphate; (4,4’-diamino-2,2’-bipyridine)nickel (II) dichloride; N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide Inert atmosphere; Sealed tube; Irradiation; chemoselective reaction;
 

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