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Chemical Structure| 1028362-85-7 Chemical Structure| 1028362-85-7

Structure of 1028362-85-7

Chemical Structure| 1028362-85-7

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Product Details of [ 1028362-85-7 ]

CAS No. :1028362-85-7
Formula : C9H15N3O
M.W : 181.23
SMILES Code : NC1=NN(C2CCCCO2)C(C)=C1
English Name :5-Methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-amine
MDL No. :MFCD20726589

Safety of [ 1028362-85-7 ]

Application In Synthesis of [ 1028362-85-7 ]

* 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 [ 1028362-85-7 ]

[ 1028362-85-7 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 1028362-85-7 ]
  • [ 1225278-66-9 ]
  • [ 2716187-03-8 ]
YieldReaction ConditionsOperation in experiment
320 mg With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 100℃; for 15h; 2.A (A) N- (5-methyl-1- (tetrahydro-2H-pyran-2-yl) -1H-pyrazol-3-yl) -4- ( (6-nitropyridin-3-yl) oxy) pyridin-2-amine 2-chloro-4- ( (6-nitropyridin-3-yl) oxy) pyridine (500 mg, 2.0 mmol) , 5-methyl-1- (tetrahydro-2H-pyran-2-yl) -1H-pyrazol-3-amine (540 mg, 3.0 mmol) , Pd2(dba)3(186 mg, 0.2 mmol) , Xantphos (116 mg, 0.2 mmol) , potassium carbonate (420 mg, 3.0 mmol) and dioxane (20 ml) were successively added to a reaction flask, and the mixture was reacted under nitrogen at 100 for 15 hours. The reaction solution was purified with flash column chromatography (dichloromethane/methanol = 100 : 0 -0 : 100, gradient elution) , to obtain 320 mg of the title product as a yellow solid. MS (m/z) : 397.0 [M+H]+.
  • 2
  • [ 717880-58-5 ]
  • [ 1028362-85-7 ]
  • [ 2902787-01-1 ]
YieldReaction ConditionsOperation in experiment
With triphenylmethanethiol; potassium carbonate 2.1 Step 1: Synthesis of methyl 2-bromo-5-((5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)amino)benzoate Methyl 2-bromo-5-iodobenzoate (5.00 g, 14.7 mmol) and 5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-amine ( 2.92 g, 16.1 mmol) was dissolved in tetrahydrofuran (200 mL), and methanesulfonic acid [9,9-dimethyl-4,5-bis(diphenylphosphine)xanthene][2'-amino-1,1 '-Biphenyl]palladium(II) dichloromethane adduct (1.39 g, 1.47 mmol) and cesium carbonate (14.3 g, 44.0 mmol). The reaction solution was stirred and reacted at 85° C. for 2 hours. LCMS detected that the reaction was complete. The reaction solution was concentrated to dryness under reduced pressure, and then purified by column chromatography (silica, petroleum ether: ethyl acetate = 2:1) to obtain 2-bromo-5-((5-methyl-1-(tetrahydro -2H-pyran-2-yl)-1H-pyrazol-3-yl)amino)benzoic acid methyl ester (1.60 g).
With triphenylmethanethiol; potassium carbonate 2.1 Step 1: Synthesis of methyl 2-bromo-5-((5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)amino)benzoate Methyl 2-bromo-5-iodobenzoate (5.00 g, 14.7 mmol) and 5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-amine ( 2.92 g, 16.1 mmol) was dissolved in tetrahydrofuran (200 mL), and methanesulfonic acid [9,9-dimethyl-4,5-bis(diphenylphosphine)xanthene][2'-amino-1,1 '-Biphenyl]palladium(II) dichloromethane adduct (1.39 g, 1.47 mmol) and cesium carbonate (14.3 g, 44.0 mmol). The reaction solution was stirred and reacted at 85° C. for 2 hours. LCMS detected that the reaction was complete. The reaction solution was concentrated to dryness under reduced pressure, and then purified by column chromatography (silica, petroleum ether: ethyl acetate = 2:1) to obtain 2-bromo-5-((5-methyl-1-(tetrahydro -2H-pyran-2-yl)-1H-pyrazol-3-yl)amino)benzoic acid methyl ester (1.60 g).
  • 3
  • [ 1028362-85-7 ]
  • [ 49668-65-7 ]
  • [ 2980688-07-9 ]
YieldReaction ConditionsOperation in experiment
51% Stage #1: 5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-amine With sodium hexamethyldisilazane In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4,6-dichloro-5-methoxy-2-(methylthio)pyrimidine In tetrahydrofuran at 80℃; for 3h; Inert atmosphere;
51 % Stage #1: 5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-amine With sodium hexamethyldisilazane In tetrahydrofuran at 20℃; Inert atmosphere; Stage #2: 4,6-dichloro-5-methoxy-2-(methylthio)pyrimidine In tetrahydrofuran at 80℃; Inert atmosphere; 1 Step 1 1 6-chloro-5-methoxy-//-(5-methyl-1-(tetrahydro-2/-/-pyran-2-yl)-1/-/-pyrazol-3-yl)-2-(methylthio)pyrimidin-4-amine A solution of NaHMDS (159.9 mL, 159.9 mmol) was added over 30 min to a solution of Intermediate 1 (9.66 g, 53.3 mmol) in THF (320 mL) at rt, under N2 atmosphere. Intermediate 3 (12.00 g, 53.31 mmol) was then added and the reaction mixture was stirred at 80°C for 3 h, at which time UPLC-MS showed complete consumption of starting material. The mixture was allowed to cool to rt and then poured into 500 ml_ of saturated aqueous NaHCO3. The resulting mixture was extracted with EtOAc (3x). The combined organics were washed with brine, dried over Na2SC>4, filtered and concentrated. The residue was purified by silica gel chromatography eluting with EtOAc (0 to 80%) in Hep to afford 6-chloro-5-methoxy-//-(5-methyl-1-(tetrahydro-2/-/-pyran-2-yl)-1H-pyrazol-3-yl)-2-(methylthio)pyrimidin-4-amine (10.0 g, 51% yield) as a light-yellow solid. UPLC-MS (+ESI) m/z = 370.0 (M+H)+ 1H NMR (400 MHz, DMSO- de) 5 ppm 1.44 - 1.56 (m, 2 H), I.58 - 1.74 (m, 1H), 1.83 (dd, J = 13.0, 2.2 Hz, 1H), 1.98 (d, J = 13.0 Hz, 1H), 2.21 - 2.28 (m, 1H), 2.30 (s, 3 H), 2.45 (s, 3 H), 3.58 - 3.68 (m, 1H), 3.74 (s, 3 H), 3.90 (d, J = 11.5 Hz, 1H), 5.32 (dd, J = 9.8, 2.2 Hz, 1H), 6.46 (s, 1H), 9.78 (s, 1H).
51 % Stage #1: 5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-amine With sodium hexamethyldisilazane In tetrahydrofuran at 20℃; Inert atmosphere; Stage #2: 4,6-dichloro-5-methoxy-2-(methylthio)pyrimidine In tetrahydrofuran at 80℃; Inert atmosphere; 1 Step 1 1 6-chloro-5-methoxy-//-(5-methyl-1-(tetrahydro-2/-/-pyran-2-yl)-1/-/-pyrazol-3-yl)-2-(methylthio)pyrimidin-4-amine A solution of NaHMDS (159.9 mL, 159.9 mmol) was added over 30 min to a solution of Intermediate 1 (9.66 g, 53.3 mmol) in THF (320 mL) at rt, under N2 atmosphere. Intermediate 3 (12.00 g, 53.31 mmol) was then added and the reaction mixture was stirred at 80°C for 3 h, at which time UPLC-MS showed complete consumption of starting material. The mixture was allowed to cool to rt and then poured into 500 ml_ of saturated aqueous NaHCO3. The resulting mixture was extracted with EtOAc (3x). The combined organics were washed with brine, dried over Na2SC>4, filtered and concentrated. The residue was purified by silica gel chromatography eluting with EtOAc (0 to 80%) in Hep to afford 6-chloro-5-methoxy-//-(5-methyl-1-(tetrahydro-2/-/-pyran-2-yl)-1H-pyrazol-3-yl)-2-(methylthio)pyrimidin-4-amine (10.0 g, 51% yield) as a light-yellow solid. UPLC-MS (+ESI) m/z = 370.0 (M+H)+ 1H NMR (400 MHz, DMSO- de) 5 ppm 1.44 - 1.56 (m, 2 H), I.58 - 1.74 (m, 1H), 1.83 (dd, J = 13.0, 2.2 Hz, 1H), 1.98 (d, J = 13.0 Hz, 1H), 2.21 - 2.28 (m, 1H), 2.30 (s, 3 H), 2.45 (s, 3 H), 3.58 - 3.68 (m, 1H), 3.74 (s, 3 H), 3.90 (d, J = 11.5 Hz, 1H), 5.32 (dd, J = 9.8, 2.2 Hz, 1H), 6.46 (s, 1H), 9.78 (s, 1H).
51 % Stage #1: 5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-amine With sodium hexamethyldisilazane In tetrahydrofuran at 20℃; Inert atmosphere; Stage #2: 4,6-dichloro-5-methoxy-2-(methylthio)pyrimidine In tetrahydrofuran at 80℃; Inert atmosphere; Step 1 1 6-chloro-5-methoxy-//-(5-methyl-1-(tetrahydro-2/-/-pyran-2-yl)-1/-/-pyrazol-3-yl)-2-(methylthio)pyrimidin-4-amine A solution of NaHMDS (159.9 mL, 159.9 mmol) was added over 30 min to a solution of Intermediate 1 (9.66 g, 53.3 mmol) in THF (320 mL) at rt, under N2 atmosphere. Intermediate 3 (12.00 g, 53.31 mmol) was then added and the reaction mixture was stirred at 80°C for 3 h, at which time UPLC-MS showed complete consumption of starting material. The mixture was allowed to cool to rt and then poured into 500 ml_ of saturated aqueous NaHCO3. The resulting mixture was extracted with EtOAc (3x). The combined organics were washed with brine, dried over Na2SC>4, filtered and concentrated. The residue was purified by silica gel chromatography eluting with EtOAc (0 to 80%) in Hep to afford 6-chloro-5-methoxy-//-(5-methyl-1-(tetrahydro-2/-/-pyran-2-yl)-1H-pyrazol-3-yl)-2-(methylthio)pyrimidin-4-amine (10.0 g, 51% yield) as a light-yellow solid. UPLC-MS (+ESI) m/z = 370.0 (M+H)+ 1H NMR (400 MHz, DMSO- de) 5 ppm 1.44 - 1.56 (m, 2 H), I.58 - 1.74 (m, 1H), 1.83 (dd, J = 13.0, 2.2 Hz, 1H), 1.98 (d, J = 13.0 Hz, 1H), 2.21 - 2.28 (m, 1H), 2.30 (s, 3 H), 2.45 (s, 3 H), 3.58 - 3.68 (m, 1H), 3.74 (s, 3 H), 3.90 (d, J = 11.5 Hz, 1H), 5.32 (dd, J = 9.8, 2.2 Hz, 1H), 6.46 (s, 1H), 9.78 (s, 1H).

 

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