* 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.
With trichlorophosphate In DMF (N,N-dimethyl-formamide) at 20 - 95℃; for 16 h;
1H-PYRAZOLE-4-CARBALDEHYDE (55). To a solution of 1- (4-METHOXY-BENZYL)-1H- pyrazole (0.21 mol) (Synth. Commun. 1990, 20/18 ; 2849) in dry DMF (235 ml) was added POCL3 (1.5 eq. ) dropwise at room temperature. The mixture was then heated at 95°C for 16 hrs. After cooling to room temperature, the reaction mixture was neutralized by adding ice and saturated sodium carbonate solution. EtOAc (800 ml) was added and the organic layer was separated and washed several times with water. After drying (Na2SO4), the solvent was removed and the crude product was purified over silica gel to give 16.4 g (35percent yield) desired aldehyde 1-(4-METHOXY-BENZYL)-LH- pyrazole-4-carbaldehyde. It was heated with 150 ml TFA for 2 hrs. TFA was evaporated and the basified crude product was purified on silica gel to give 5.3 g of 55.
With potassium carbonate In acetonitrile for 1 h; Reflux
To a mixture of 1H-pyrazole-4-carbaldehyde (100 mg, 1.04 mmol) and 1- (chloromethyl)-4-methoxybenzene (162 mg, 1.04 mmol) in CH3CN (6 mL) was added potassium carbonate (287 mg, 2.08 mmol), the resulting mixture was stirred at reflux for 1 h. The mixture was poured into water (20 mL) and extracted with EtOAc (3×20 mL). The organic layer was dried over Na2SO4and concentrated to give 1-(4-methoxybenzyl)- 1H-pyrazole-4-carbaldehyde (220 mg, 93.3 percent) as a colorless oil
Reference：
[1] Patent: KR2017/45749, 2017, A, . Location in patent: Paragraph 1087; 1090-1092
4
[ 145162-51-2 ]
[ 68-12-2 ]
[ 153687-35-5 ]
Reference：
[1] Journal of Heterocyclic Chemistry, 1993, vol. 30, # 4, p. 957 - 960
[2] Tetrahedron, 1995, vol. 51, # 16, p. 4779 - 4800
5
[ 824-94-2 ]
[ 153687-35-5 ]
Reference：
[1] Journal of Heterocyclic Chemistry, 1993, vol. 30, # 4, p. 957 - 960
With trichlorophosphate; In DMF (N,N-dimethyl-formamide); at 20 - 95℃; for 16.0h;
1H-PYRAZOLE-4-CARBALDEHYDE (55). To a solution of 1- (4-METHOXY-BENZYL)-1H- pyrazole (0.21 mol) (Synth. Commun. 1990, 20/18 ; 2849) in dry DMF (235 ml) was added POCL3 (1.5 eq. ) dropwise at room temperature. The mixture was then heated at 95C for 16 hrs. After cooling to room temperature, the reaction mixture was neutralized by adding ice and saturated sodium carbonate solution. EtOAc (800 ml) was added and the organic layer was separated and washed several times with water. After drying (Na2SO4), the solvent was removed and the crude product was purified over silica gel to give 16.4 g (35% yield) desired aldehyde 1-(4-METHOXY-BENZYL)-LH- pyrazole-4-carbaldehyde. It was heated with 150 ml TFA for 2 hrs. TFA was evaporated and the basified crude product was purified on silica gel to give 5.3 g of 55.
With trifluoroacetic acid; for 2h;Heating / reflux;
1H-PYRAZOLE-4-CARBALDEHYDE (55). To a solution of 1- (4-METHOXY-BENZYL)-1H- pyrazole (0.21 mol) (Synth. Commun. 1990, 20/18 ; 2849) in dry DMF (235 ml) was added POCL3 (1.5 eq. ) dropwise at room temperature. The mixture was then heated at 95°C for 16 hrs. After cooling to room temperature, the reaction mixture was neutralized by adding ice and saturated sodium carbonate solution. EtOAc (800 ml) was added and the organic layer was separated and washed several times with water. After drying (Na2SO4), the solvent was removed and the crude product was purified over silica gel to give 16.4 g (35percent yield) desired aldehyde 1-(4-METHOXY-BENZYL)-LH- pyrazole-4-carbaldehyde. It was heated with 150 ml TFA for 2 hrs. TFA was evaporated and the basified crude product was purified on silica gel to give 5.3 g of 55.
With potassium carbonate; In acetonitrile; for 1h;Reflux;
To a mixture of 1H-pyrazole-4-carbaldehyde (100 mg, 1.04 mmol) and 1- (chloromethyl)-4-methoxybenzene (162 mg, 1.04 mmol) in CH3CN (6 mL) was added potassium carbonate (287 mg, 2.08 mmol), the resulting mixture was stirred at reflux for 1 h. The mixture was poured into water (20 mL) and extracted with EtOAc (3×20 mL). The organic layer was dried over Na2SO4and concentrated to give 1-(4-methoxybenzyl)- 1H-pyrazole-4-carbaldehyde (220 mg, 93.3 percent) as a colorless oil
N-(azetidin-3-yl)-1-cyclopropyl-1H-1,2,3-triazole-4-carboxamide[ No CAS ]
[ 153687-35-5 ]
1-cyclopropyl-N-(1-((1-(4-methoxybenzyl)-1H-pyrazol-4-yl)methyl)azetidin-3-yl)-1H-1,2,3-triazole-4-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
53.9%
To a mixture of N-(azetidin-3-yl)-1-cyclopropyl-1H-1,2,3-triazole-4-carboxamide (50 mg, 0.2412 mmol) and <strong>[153687-35-5]1-(4-methoxybenzyl)-1H-pyrazole-4-carbaldehyde</strong> (62.5 mg, 0.2894 mmol) in methanol (5 mL) was added acetic acid (724 mug, 0.01206 mmol), the mixture was stirred at r.t. for 15 min, then sodium cyanoborohydride (30.3 mg, 0.4824 mmol) was added, the resulting mixture was stirred at 40oC overnight. The mixture was concentrated under reduced pressure. The residue was dissolved in aqueous solution of Na2CO3and extracted with EtOAc (3×20 mL). The organic layer was dried over Na2SO4and concentrated. The residue was purified by prep-TLC (CH2Cl2/NH3.MeOH=20/1) to give1-cyclopropyl-N-(1-((1-(4-methoxybenzyl)-1H-pyrazol-4-yl)methyl)azetidin-3-yl)- 1H-1,2,3-triazole-4-carboxamide (53 mg, 53.9 %) as a white solid
N-[[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]methylene]-2-methyl-propane-2-sulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
With tris(2,2,2-trifluoroethyl) borate; In tetrahydrofuran; at 20℃; for 96.0h;Inert atmosphere;
General procedure: The aldehyde (4.62 mmol, 1 equivalent) and 2-methylpropane-2-sulfonamide (0.76 g, 5.55 mmol, 1.2 equivalents) were dissolved in anhydrous THF (10 mL) under an atmosphere of nitrogen with stirring. The concentration of the reaction with respect to the aldehyde was 0.46 M. Tris(2,2,2-trifluoroethyl) borate (1.095 mL, 5.09 mmol) was added dropwise to the stirred reaction mixture at room temperature and the reaction was stirred for approximatively 4 days or until UPLC analysis indicated the reaction was complete. The reaction mixture was diluted with EtOAc (50 mL), washed sequentially with a saturated aqueous solution of NaHCO3 (35 mL) and water (35 mL). The organic layer was then dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford the product tert-butyl sulfonyl imines. Some of the products were prone to hydrolysis and unstable to flash chromatography, so were used directly in the subsequent cyclisation step unless specified.
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