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CAS No. : | 29274-24-6 | MDL No. : | MFCD04035683 |
Formula : | C6H4ClN3 | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | WEPRLWNMBTYGGD-UHFFFAOYSA-N |
M.W : | 153.57 | Pubchem ID : | 21071759 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | |
Hazard Statements: | H302-H315-H319-H332-H335 | Packing Group: | |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With potassium fluoride; In dimethyl sulfoxide; at 180℃; for 2h; | A mixture of 5-chloropyrazolo[1,5-a]pyrimidine (1.18 g, 7.68 mmol), <strong>[1218935-59-1](R)-2-(2,5-difluorophenyl)pyrrolidine</strong> (1.51 g, 8.22 mmol) and KF (2.32 g, 39.1 mmol) in DMSO (26 mL) was heated at 180 C. for 2 hours. The reaction mixture was cooled to room temperature and poured into water. The mixture was stirred for additional 30 min at room temperature. A precipitated solid was collected by filtration and dried under vacuum to afford (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine (1.70 g, 74%) as a yellow solid. 1H-NMR (DMSO-d6, Varian, 400 MHz): delta 1.88-2.06 (3H, m), 2.33-2.45 (1H, m), 3.56-3.70 (1H, m), 3.90-4.00 (1H, m), 5.38 (1H, s), 5.98 (1H, s), 6.10-6.50 (1H, m), 6.85-6.91 (1H, m), 7.10-7.15 (1H, m), 7.26-7.32 (1H, m), 7.81 (1H, d, J=1.6 Hz), 8.60 (1H, s). |
68% | With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 160℃;Sealed tube; | Preparation B; Preparation of (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-l-yl)pyrazolo?,5-alpyrimidin-3- amine; [00381] Step A: Preparation of (RV5-(2-(2.5-difluorophenyr)pyrrolidin-l- yPpyrazolo [ 1 ,5 -a"|pyrimidine; In a pressure reaction tube was added 5-chloropyrazolo[l,5- a]pyrimidine (4.2 g, 27 mmol), <strong>[1218935-59-1](R)-2-(2,5-difluorophenyl)pyrrolidine</strong> (Preparation A; 5.3 g, 29 mmol), anhydrous n-butanol (5 ml, 55 mmol), and DIEA (9.5 ml, 55 mmol). The yellowish suspension was sealed and heated in an oil bath (160 0C) overnight. The reaction was cooled to ambient temperature, diluted with EtOAc (250 mL), and filtered, rinsing the solid with EtOAc. The filtrate (330 mL) was washed with water (2 x 150 mL), brine (100 mL), concentrated, and purified by silica chromatography, eluting with 2:1 EtOAc/hexanes to give the product as a bright yellowish solid (5.6 g, 68% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With bis-triphenylphosphine-palladium(II) chloride; triethylamine; at 100.0℃; under 7600.51 Torr; | A mixture of 5-chloro-pyrazolo[1,5-a]pyrimidine (2 g, 13.02 mmol, 1 .00 equiv), triethylamine (4 mL), methanol (80 mL), and bis(triphenylphosphine)palladium(U) dichloride (1 g, 1.42 mmol, 0.1 1 equiv) was stirred in a 100-mL pressure reactor overnight at 100 "C under 10 atmospheres of carbon monoxide. The reaction mixture was cooled to rt then concentrated under vacuum. The residue was purified on a silica gel column eluted with ethyl acetate/petroleum ether (1 :5) to yield 1 .2 g (52%) of the title compound as a light yellow solid. LC/MS (Method I, ESI): RT= 1 .09 min, m/z 178.0 [M+H] |
52% | With triethylamine; at 100.0℃; under 7600.51 Torr;Sealed tube; | A mixture of 5-chloro-pyrazolo[1,5-a]pyrimidine (2 g, 13.02 mmol, 1 .00 equiv), triethylamine (4 mL), methanol (80 mL), and bis(triphenylphosphine)palladium(U) dichloride (1 g, 1.42 mmol, 0.1 1 equiv) was stirred in a 100-mL pressure reactor overnight at 100 "C under 10 atmospheres of carbon monoxide. The reaction mixture was cooled to rt then concentrated under vacuum. The residue was purified on a silica gel column eluted with ethyl acetate/petroleum ether (1 :5) to yield 1 .2 g (52%) of the title compound as a light yellow solid. LC/MS (Method I, ESI): RT= 1 .09 min, m/z 178.0 [M+H] |
52% | With bis-triphenylphosphine-palladium(II) chloride; triethylamine; at 100.0℃; under 7600.51 Torr;Sealed tube; | A mixture of 5-chloro-pyrazolo[1,5-a]pyrimidine (2 g, 13.02 mmol, 1 .00 equiv), triethylamine (4 mL), methanol (80 mL), and bis(triphenylphosphine)palladium(U) dichloride (1 g, 1.42 mmol, 0.1 1 equiv) was stirred in a 100-mL pressure reactor overnight at 100 "C under 10 atmospheres of carbon monoxide. The reaction mixture was cooled to rt then concentrated under vacuum. The residue was purified on a silica gel column eluted with ethyl acetate/petroleum ether (1 :5) to yield 1 .2 g (52%) of the title compound as a light yellow solid. LC/MS (Method I, ESI): RT= 1 .09 min, m/z 178.0 [M+H] |
52% | With bis-triphenylphosphine-palladium(II) chloride; triethylamine; at 100.0℃; under 7600.51 Torr; | [0211] Step 3. Pyrazolo[1,5-alpyrimidine-5-carboxylic acid methyl ester. A mixture of 5- chloro-pyrazolo[1,5-a]pyrimidine (2 g, 13.02 mmol, 1.00 equiv), triethylamine (4 mL), methanol (80 mL), and bis(triphenylphosphine)palladium(II) dichloride (1 g, 1.42 mmol, 0.11 equiv) was stirred in a 100-mL pressure reactor overnight at 100 C under 10 atmospheres of carbon monoxide. The reaction mixture was cooled to rt then concentrated under vacuum.The residue was purified on a silica gel column eluted with ethyl acetate/petroleum ether (1:5) to yield 1.2 g (52%) of the title compound as a light yellow solid. LC/MS (Method I, ESI): RT= 1.09 mi m/z = 178.0 [M+Hf?. |
52% | With bis-triphenylphosphine-palladium(II) chloride; triethylamine; at 100.0℃; under 7600.51 Torr; | [0219] Step 3. PyrazolorL5-alpyrimidine-5-carboxylic acid methyl ester. A mixture of 5- chloro-pyrazolo[l,5-a]pyrimidine (2 g, 13.02 mmol, 1.00 equiv), triethylamine (4 mL), methanol (80 mL), and bis(triphenylphosphine)palladium(II) dichloride (1 g, 1.42 mmol, 0.11 equiv) was stirred in a 100-mL pressure reactor overnight at 100 C under 10 atmospheres of carbon monoxide. The reaction mixture was cooled to rt then concentrated under vacuum. The residue was purified on a silica gel column eluted with ethyl acetate/petroleum ether (1 :5) to yield 1.2 g (52%) of the title compound as a light yellow solid. LC/MS (Method I, ESI): RT= 1.09 min, m/z = 178.0 [M+H]+. |
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