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Chemical Structure| 41095-07-2 Chemical Structure| 41095-07-2

Structure of 41095-07-2

Chemical Structure| 41095-07-2

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Product Details of [ 41095-07-2 ]

CAS No. :41095-07-2
Formula : C12H14ClN3O2
M.W : 267.71
SMILES Code : O=C(C1=C(C)N=C(N(CC)N=C2)C2=C1Cl)OCC
MDL No. :MFCD18073648

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Application In Synthesis of [ 41095-07-2 ]

* 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 [ 41095-07-2 ]

[ 41095-07-2 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 3528-58-3 ]
  • [ 3044-06-2 ]
  • [ 41095-07-2 ]
YieldReaction ConditionsOperation in experiment
57.17% A mixture of l-ethyl-lH-pyrazol-5-amine (16 gm, 0.144 moles) (example 2) and 2-(l-ethoxy-ethylidene)-malonic acid diethyl ester (29 gm, 0.12 moles) (example 3) was stirred at 1200C for about 2 hrs. When the reaction was complete on TLC, crude reaction mixture was concentrated in vacuo to remove ethanol, which was formed as byproduct. Crude residue was taken in phosphorous oxychloride (50 ml) and heated at 115 C for about 12-13 hrs. The reaction mixture was poured into ice-cooled water with continuous stirring. Solid which precipitated out was filtered and dried under vacuum to afford title compound as creamy white solid.Yield: 12 gm (57.17%) m/z: (M++l) 268.28
Intermediate 11: Ethyl 4-chloro-1-ethyl-6-methyl-lH-pyrazolo [3, 4-b] pyridine-5- carboxylate; A mixture of 5-amino-1-ethylpyrazole (1.614g, 14. 5mmol) and diethyl 2- (1- ethoxyethylidene) malonate (3.68g, 16. 0mmol, as described by P. P. T. Sah, J. Amer. Chem. Soc., 1931,53, 1836) was heated at 150 C under Dean Stark conditions for 5 hours. Phosphorous oxychloride (25ml) was carefully added to the mixture and the resulting solution was heated at 130 C under reflux for 18 hours. The mixture was concentrated in vacuo, then the residual oil was carefully added, with cooling, to water (100ml). The resulting mixture was extracted with DCM (3xlOOml) and the combined organic extracts were dried over anhydrous sodium sulphate and concentrated in vacuo. The residual oil was purified by Biotage chromatography (silica, 90g) eluting with ethyl acetate-petrol (1: 19). Fractions containing the desired product were combined and concentrated in vacuo to afford Intermediate 58 (1. 15g). LCMS showed MH+ = 268 ; TpBT = 3. 18min
A mixture of 5-amino-1-ethylpyrazole (1.614g, [14.] [5MMOL)] and diethyl [2- (1-] ethoxyethylidene) malonate (3.68g, [16.] [0MMOL,] as described by P. P. T. Sah, [J AMER.] Chem. Soc., 1931,53, 1836) was heated at [150 C] under Dean Stark conditions for 5 hours. Phosphorous oxychloride [(25ML)] was carefully added to the mixture and the resulting solution was heated at [130 C] under reflux for 18 hours. The mixture was concentrated in vacuo, then the residual oil was carefully added, with cooling, to water [(100ML).] The resulting mixture was extracted with DCM [(3XLOOML)] and the combined organic extracts were dried over anhydrous sodium sulphate and concentrated in vacuo. The residual oil was purified by Biotage chromatography (silica, 90g) eluting with ethyl acetate-petrol (1: 19). Fractions containing the desired product were combined and concentrated in vacuo to afford Intermediate 51 (1.15g). LCMS showed MH+ = 268; TRET = 3. [18MIN.]
A mixture of 5-amino-1-ethylpyrazole (1.614 g, 14.5 mmol) and <strong>[3044-06-2]diethyl 2-(1-ethoxyethylidene)malonate</strong> [J. Am. Chem. Soc., 1931, 53, 1836] (3.68 g) was heated at 150 C. under Dean Stark conditions for 5 hours. Phosphorous oxychloride (25 ml) was carefully added to the mixture and the resulting solution was heated at 130 C. under reflux for 18 hours. The mixture was concentrated in vacuo and the residual oil was carefully added, with cooling, to water (100 ml). The resulting mixture was extracted with dichloromethane (3*100 ml) and the combined organic extracts were dried over anhydrous sodium sulphate and concentrated in vacuo. The residual oil was purified by Biotage chromatography (silica; 90 g) eluding with 5% ethyl acetate in petroleum ether. Fractions containing the desired product were combined and concentrated in vacuo to give Intermediate 17 (1.15 g). LCMS showed MH+=268; TRET=3.18 min.
Intermediate 17: Ethyl 4-chloro-1-ethyl-6-methyl-1H-pyrazolo[3,4-Jb]pyridine-5- carboxylate EPO <DP n="145"/>A mixture of 5-amino-i-ethylpyrazole (1.614g, 14.5mmol) and diethyl 2-(1- ethoxyethylidene)malonate [J. Am. Chem. Soc, 1931, 53, 1836 (3.68g) was heated at 150 0C under Dean Stark conditions for 5 hours. Phosphorous oxychloride (25ml) was carefully added to the mixture and the resulting solution was heated at 130 0C under reflux for 18 hours. The mixture was concentrated in vacuo and the residual oil was carefully added, with cooling, to water (100ml). The resulting mixture was extracted with dichloromethane (3 x 100ml) and the combined organic extracts were dried over anhydrous sodium sulphate and concentrated in vacuo. The residual oil was purified by Biotage chromatography (silica; 9Og) eluting with 5% ethyl acetate in petroleum ether. Fractions containing the desired product were combined and concentrated in vacuo to give Intermediate 17 (1.15q). LCMS showed MH+ = 268; TREtau = 3.18min.

  • 2
  • [ 33024-60-1 ]
  • [ 41095-07-2 ]
  • [ 675114-55-3 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 85℃; for 24h;Product distribution / selectivity; Alternative preparation of ethyl 1-ethyl-6-methyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxylate: 4-Aminotetrahydro-2/-/-pyran hydrochloride (e.g. see Intermediate 8A of WO 2004/024728 A2, 0.413g, 3.0mmol) is added to a mixture of ethyl 4-chloro-1-ethyl-6- methyl-1/-/-pyrazolo[3,4-]pyhdine-5-carboxylate (0.268g, LOmmol) and DIPEA (0.87ml, delta.Ommol) in MeCN (3ml). The resulting mixture is heated at 85 0C for 24 hours.Volatiles are removed in vacuo and the residue is dissolved in chloroform (1.5ml) and applied to a SPE cartridge (silica, 5g). The cartridge is eluted successively with Et2O, EtOAc and EtOAc-MeOH (9:1). Fractions containing the desired product (which might be contaminated with starting material) are combined and concentrated in vacuo. Further purification using a SPE cartridge (silica, 5g) eluting with EtOAc-cyclohexane (1 :3) affords ethyl 1-ethyl-6-methyl-4-(tetrahydro-2H-pyran-4-ylamino)-1/-/-pyrazolo[3,4- ]pyridine-5-carboxylate.
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 85℃; for 24h; 4-Aminotetrahydropyran hydrochloride (Intermediate 8A, 0. [413G,] 3. 0mmol) was added to a mixture of Intermediate 51 (0.268g, [L.] Ommol) and N, N-diisopropylethylamine (0. [87ML,] [5.] [0MMOL)] in acetonitrile (3ml). The resulting mixture was heated at [85 °C FOR] 24 hours. Volatiles were removed in vacuo and the residue was dissolved in chloroform (1. [5ML)] and applied to a SPE cartridge (silica, 5g). The cartridge was eluted successively with [ET20,] EtOAc and EtOAc-MeOH (9/1). Fractions containing the desired product were combined and concentrated in vacuo to give the desired product contaminated with starting material (Intermediate [51).] Further purification using a SPE cartridge (silica, 5g) eluting with ethyl acetate-cyclohexane (1/3) afforded Example 189 (0.248g). LCMS showed [MH+ =] 333; [TRET] = 2.75min.
 

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