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Chemical Structure| 14521-81-4 Chemical Structure| 14521-81-4

Structure of 14521-81-4

Chemical Structure| 14521-81-4

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Product Details of [ 14521-81-4 ]

CAS No. :14521-81-4
Formula : C3H3FN2
M.W : 86.07
SMILES Code : FC1=NNC=C1
MDL No. :MFCD18205877
InChI Key :WNDHCIJGEKNYNF-UHFFFAOYSA-N
Pubchem ID :15055508

Safety of [ 14521-81-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H317-H319
Precautionary Statements:P280-P305+P351+P338

Application In Synthesis of [ 14521-81-4 ]

* 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 [ 14521-81-4 ]

[ 14521-81-4 ] Synthesis Path-Downstream   1~9

  • 2
  • tert-butyl 4-[[1-(3-bromophenyl)-4-oxo-1H,4H,5H-pyrazolo[3,4-d]pyrimidin-5-yl]methyl]-4-hydroxypiperidine-1-carboxylate [ No CAS ]
  • [ 14521-81-4 ]
  • tert-butyl 4-([1-[3-(3-fluoro-1H-pyrazol-1-yl)phenyl]-4-oxo-1H,4H,5H-pyrazolo[3,4-d]pyrimidin-5-yl]methyl)-4-hydroxypiperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
34% With copper(l) iodide; (1R,2R)-1,2-diaminocyclohexane; potassium carbonate; In 1,4-dioxane; at 100℃; for 16h;Inert atmosphere; A 50-mE 3-necked round-bottom fitted with a nitrogen balloon, magnetic stir bar condenser and thermometer was charged with tert-butyl 4-[[ 1 -(3-bromophenyl)-4-oxo- 1 H,4H,5H-pyrazolo[3,4-d]pyrimidin-5-yl]methyl] -4-hy- droxypiperidine- 1 -carboxylate (Intermediate 30a, 294 mg, 0.58 mmol), 1 ,4-dioxane (10 mE), 3-fluoro-l H-pyrazole (100 mg, 1.16 mmol), Cul (5.7 mg, 0.03 mmol), potassium carbonate (248 mg, 1.79 mmol) and (1R,2R)-cyclohexane-l,2- diamine (17 mg, 0.15 mmol). The resulting mixture was stirred for 16 hat 1000 C. under nitrogen. After cooling to 25 C., the reaction was quenched with water (10 mE). The product was extracted with ethyl acetate (3x20 mE). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was purified by column chromatography eluting with dichloromethane/ethyl acetate (5:1-2:1, v/v) to give tert-butyl 4-al - [3-(3-fluoro-l H-pyrazol- 1 -yl)phenyl]-4-oxo-l H,4H,5H- pyrazolo[3,4-d]pyrimidin-5-yl]methyl)-4- hydroxypiperidine- 1 -carboxylate (100 mg, 34%). LCMS:(ES) mlz 510 [M+H].
  • 3
  • (R)-5-chloro-N-(1-cyclopropyl-2,2,2-trifluoroethyl)-7-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide [ No CAS ]
  • [ 14521-81-4 ]
  • (R)-N-(1-cyclopropyl-2,2,2-trifluoroethyl)-5-(3-fluoro-1H-pyrazol-1-yl)-7-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
33% With potassium carbonate; In tetrahydrofuran; at 70℃; for 8h; To a solution of (R)-5-chloro-N-(1 -cyclopropyl-2,2,2-trifluoroethyl)-7-methylpyrazolo[1,5-ajpyrimidine-3-carboxamide (80 mg, 0.24 mmol) in anhydrous THF (3mL) was added <strong>[14521-81-4]3-fluoro-1H-pyrazole</strong> (25 mg, 0.288 mmol) and K2C03 (100 mg, 0.72 mmol). The mixture was stirred at 70 C for 8 h, poured into H20 (20 mL) and extracted with EA (20 mL x 2). The organic layers were dried over anhydrous Na2SO4, and filtered. The filtrate wasconcentrated in vacuo and the residue was purified by preparative TLC (PE/EA = 2/1) to affordthe title compound (30 mg, 33 %) as a white solid. ?H NMR (500 MI-Tz, DMSO-d6) oe 8.65 (s,1H), 8.62 (t, J= 3.0 Hz, 1H), 8.14 (d, J= 9.5 Hz, 1H), 7.67 (s, 1H), 6.67 (q, J= 3.0 Hz, 1H),4.33-4.27 (m, 1H), 2.86 (s, 3H), 1.47-1.23 (m, 1H), 0.73-0.56 (m, 3H), 0.39-0.36 (m, 1H). LCMS m/z: 383.1 [M+Hf?. HPLC Purity (214 nm): 96.46 %; tR= 8.82 mm.
  • 4
  • (S)-5-chloro-N-(1-cyclopropyl-2,2,2-trifluoroethyl)-7-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide [ No CAS ]
  • [ 14521-81-4 ]
  • (S)-N-(1-cyclopropyl-2,2,2-trifluoroethyl)-5-(3-fluoro-1H-pyrazol-1-yl)-7-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 2h; A mixture of (5)-S -chloro-N-( 1 -cyclopropyl-2,2,2-trifluoroethyl)-7-methylpyrazolo[ 1,5 -aj pyrimidine-3 -carboxamide (70 mg, 0.21 mmol), 3-fluoro- 1H-pyrazole(18 mg, 0.21 mmol), and K2C03 (58 mg, 0.42 mmol) in DMF (2 mL) was stirred at 60 C for 2 h, poured into H20 (10 mL), and extracted with EA (30 mL x 3). The combined organic phases were washed with H20 (50 mL) and brine (50 mL), dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo, and the residue was purified by silica gel columnchromatography (PE/EA = 2/1) and preparative HPLC (10 mM NH4HCO3/MeCN) to afford thetitle compound (14 mg, 24%) as a white solid. ?H NMR (400 MHz, MeOD-d4): 5 8.59 (s, 1H),8.55 (t, J= 2.4 Hz, 1H), 7.65 (s, 1H), 7.44 (q, J= 2.8 Hz, 1H), 4.36-4.30 (m, 1H), 2.92 (s, 3H),1.40-1.34 (m, 1H), 0. 82-0.75 (m, 1H), 0.70-0.58 (m, 2H), 0.52-0.46 (m, 1H). LC-MS m/z:383.1 [M+Hj. HPLC: Purity (214 nm): 93%; tR= 8.83 min.
  • 5
  • [ 14521-81-4 ]
  • [ 206193-17-1 ]
  • (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(3-fluoro-1H-pyrazol-1-yl)-2-hydroxy-2-methylpropanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.36 g (5)-N-(4-Cyano-3-(trifluoromethyl)phenyl)-3-(3-fluoro-lH-pyrazol- l-yl)-2-hydroxy-2- methylpropanamide Ci5Hi2F4N402 (1012) (0755) (0756) [00344] To a solution of 3-fluoro-pyrazole (0.20 g, 0.00232 mol) in anhydrous THF (10 mL), which was cooled in an ice water bath under an argon atmosphere, was added sodium hydride (60% dispersion in oil, 0.24 g, 0.00582 mol). After addition, the resulting mixture was stirred for 3 h. (7?)- 3-Bromo-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-2-methylpropanamide (8, 0.82 g, 0.00232 mol) was added to above solution, and the resulting reaction mixture was allowed to stir overnight at RT under argon. The reaction was quenched by water, and extracted with ethyl acetate. The organic layer was washed with brine, dried with MgS04, filtered, and concentrated under vacuum. The product was purified by a silica gel column using ethyl acetate and hexanes (2: 1) as eluent to afford 0.36 g of the compound as white needles. (0757) [00345] Compound 1012 was characterized as follows: lH NMR (400 MHz, DMSO-i delta 10.39 (s, 1H, NH), 8.47 (d, = 2.0 Hz, 1H, ArH), 8.24 (dd, = 8.8 Hz, = 2.0 Hz, 1H, ArH), 8.11 (d, = 8.8 Hz, 1H, ArH), 7.55 (t, J = 3.0 Hz, 1H, Pyrazole-H), 6.29 (s, 1H, OH), 5.93-5.91 (m, 1H, Pyrazole- H), 4.34 (d, = 13.6 Hz, 1H, CH), 4.15 (d, = 13.6 Hz, 1H, CH), 1.36 (s, 3H, CH3); Mass (ESI, Positive): 357.0966 [M+H]+.
  • 6
  • 4,6-dichloro-N-(4,4-difluorocyclohexyl)pyrimidin-2-amine [ No CAS ]
  • [ 14521-81-4 ]
  • C13H13ClF3N5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
32% With caesium carbonate; In acetonitrile; at 80℃; for 8h; To a stirred solution of 4, 6-dichloro-N-(4, 4-difluorocyclohexyl) pyrimidin-2-amine (1 g, 3.54 mmol) in acetonitrile (10 mL) was added 3-fluoro pyrazole (0.36 g, 4.25 mmol) and cesium carbonate (2.30 g, 7.089 mmol). The reaction mixture was heated at 80 C for 8h. The reaction mixture was filtered and the filtrate was concentrated to afford crude product and which was purified by column chromatography (60-120 mesh) using 22% ethyl acetate in pet ether as solvent to afford 4, 6-dichloro-N-(4, 4- difluorocyclohexyl) pyrimidin-2-amine [Bj as an off-white solid (4 g, 32%). MS (M, M+2)=282.0, 284.1.
  • 7
  • 2-chloro-N-(2,4-dimethoxybenzyl)-5-nitrobenzenesulfonamide [ No CAS ]
  • [ 14521-81-4 ]
  • N-(2,4-dimethoxybenzyl)-2-(3-fluoro-1H-pyrazol-1-yl)-5-nitrobenzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In acetonitrile; at 120℃; for 4h;Microwave irradiation; To a solution of 2-chloro-N-(2 ,4-d imethoxybenzyl)-5-n itrobenzenesulfonamide (700 mg, 1.81 mmol) in acetonitrile (19 mL) were added <strong>[14521-81-4]3-fluoro-1H-pyrazole</strong> (234 mg, 2.71 mmol,CAS-RN 14521-81-4) and powdered potassium carbonate (750 mg, 5.43 mmol) and the mixture was irradiated for 2h at 120C in the microwave. 3-Fluoro-1H-pyrazole (234 mg,2.71 mmol) was added, and microwave irradiation was continued for 2h at 120C. The reaction mixture was filtered and concentrated in vacuo, and the residue was extracted with dichloromethane and water. The aqueous phase was washed three times withdichloromethane. Then the combined organic phases were washed with brine and dried using a Whatman filter. Concentration under reduced pressure led to the title compound that was purified by flash chromatography (567 mg, 61% yield, 85% purity). LC-MS (Method B): Rt = 1.25 mm; MS (ESIpos): mlz = 437 [M+H]1HNMR (400MHz, DMSO-d6) oe [ppm]: 3.52 (s, 3H), 3.63 (s, 3H), 4.14 (s, 2H), 6.19 (d,1H), 6.28 (dd, 1H), 6.46 (dd, 1H), 7.06 (d, 1H), 7.82 (d, 1H), 8.04 (s, 1H), 8.23 (dd, 1H),8.26 (d, 1H), 8.44 (dd, 1H).
  • 8
  • [ 4399-47-7 ]
  • [ 14521-81-4 ]
  • 1-cyclobutyl-3-fluoro-1H-pyrazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
<strong>[14521-81-4]3-fluoro-1H-pyrazole</strong> (150 mg, 2.91 mmol) were dissolved in DMF (10 mL) at RT. Sodium hydride (152 mg, 3.49 mmol, 1 .2 eq) was added and the mixture stirred for 10 min. Then cyclobutylbromide (0.82 mL, 8.71 mmol, 3 eq. ) was added and the mixture stirred for 2 h at 50 C. After cooling to RT, the mixture was poured into water and extracted 4x with ethyl acetate. The combined organic layers were washed with brine, dried with sodium sulfate and the solvents removed in vacuo. The crude product afforded no further purification: 400 mg (98% of theory) pale yellow oil. 1H NMR (400 MHz, DMSO-d6) delta [ppm] 1 .68 - 1 .79 (m, 2H), 2.28 -2.43 (m, 4H), 4.88 (quint, 1 H), 5.91 (dd, 1 H), 7.71 (t, 1 H). LCMS (method 1 ): Rt = 0.84 min; MS (ESIPos) m/z = 141 (M+H)
  • 9
  • [ 1259327-69-9 ]
  • [ 14521-81-4 ]
  • N-(4-cyano-3-(trifluoromethyl)phenyl)-2-(3-fluoro-1H-pyrazol-1-yl)-2-methylpropanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
30% With potassium phosphate; copper(I) bromide dimethylsulfide complex; triphenylphosphine; sodium hydroxide; In toluene; at 50℃; for 12h;Inert atmosphere; In a 100 mL round bottom flask, add 2-bromo-N- (4-cyano-3-trifluoromethyl-phenyl) -2-methylpropanamide (0.40 g, 1.1936 mmol), 3-fluoro-1H -Pyrazole (0.21 g, 2.38727 mmol), cuprous bromide dimethyl sulfide (25 mg, 0.11936 mmol), triphenylphosphine (31 mg, 0.11936 mmol), tripotassium phosphate (0.304 g, 1.4323 mmol), sodium hydroxide (53 mg, 1.3130 mmol), 10 mL of anhydrous toluene as a solvent. The resulting mixture was heated to 50 C and stirred for 12 hours under the protection of argon. After confirming the completion of the reaction by thin layer chromatography, the reaction solution was cooled to 20 ± 5 C, then water (30 ml) and ethyl acetate (35 ml) were added, and after a short stirring, the liquid was separated, and the organic phase was washed with brine (25 ml), Magnesium sulfate was dried, filtered, and the organic phase was drained to obtain an oily substance. Separated by silica gel column chromatography (mobile phase: hexane: ethyl acetate = 3: 1 to 2: 1), purified to obtain 0.12 g of white powder, which was identified as N- (4-cyano-3-trifluoro Methyl) phenyl-2- (3-fluoro-1H-pyrazol-1-yl) -2-methylpropionamide. The yield is 30%.
 

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