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CAS No. : | 82560-12-1 | MDL No. : | MFCD00067987 |
Formula : | C7H13N3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ZHBXGHWSVIBUCQ-UHFFFAOYSA-N |
M.W : | 139.20 | Pubchem ID : | 522787 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
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 |
---|---|---|
31% | With copper(l) iodide; (R,R)-N,N'-dimethyl-1,2-diaminocyclohexane; potassium carbonate; In toluene; for 16h;Inert atmosphere; Reflux; | Intermediate A19: 3-ferf-Butyl-1 -(3,4-dimethoxyphenyl)-1W-pyrazol-5-amine.Intermediate A19To a solution of 4-iodo-1 ,2-dimethoxybenzene (1 .10 g, 4.17 mmol) in anhydrous toluene (5.0 mL) was added 3-ierf-butyl-1 - -pyrazol-5-amine (638 mg, 4.58 mmol) followed by (1 R,2f?)- /V1,A 2-dimethylcyclohexane-1 ,2-diamine (130 μ, 0.83 mmol) and potassium carbonate (1.15 g, 8.3 mmol). The mixture was purged with N2, copper(l) iodide (40 mg, 0.21 mmol) was added and the reaction mixture was heated at reflux under N2 for 16 hr. The resulting mixture was cooled to RT and was partitioned between EtOAc (100 mL) and water (150 mL). The organic layer was separated and was washed with aq. citric acid solution (10% w/v, 50 mL) followed by brine (50 mL) and then dried and evaporated in vacuo. The residue was purified by flash column chromatography (S1O2, 80 g, EtOAc in isohexane, 0-70%, gradient elution). The impure product so obtained was dissolved in ether (1.0 mL), isohexane (10 mL) was added and the resulting precipitate was collected by filtration to afford the title compound, Intermediate A19, as a purple solid (364 mg, 31 %); R' 3.55 min (Method 1 ); m/z 276 (M+H)+ (ES+). Intermediate 20: 3-ferf-Butyl-1 -(4-methylthiophen-2-yl)-1W-pyrazol-5-amine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With copper(l) iodide; potassium carbonate; trans-N,N'-dimethylcyclohexane-1,2-diamine; In toluene; at 135 - 140℃; for 5.0h;Microwave irradiation; Inert atmosphere; | a. 3-(5-Amino-3-tert-butyl-pyrazol-1-yl)-5-methyl-phenol (Intermediate 54a) 5-tert-Butyl-2H-pyrazol-3-ylamine (1.11 g, 8.00 mmol), potassium carbonate (2.32 g, 16.8 mmol), copper (I) iodide (0.076 g, 0.40 mmol), and <strong>[74204-00-5]3-bromo-5-methylphenol</strong> (1.80 g, 9.60 mmol) were weighed into a large microwave vial. This was then purged with argon then trans-N,N-dimethylcyclohexane-1,2-diamine (0.25 mL, 1.60 mmol) added. To this mixture was then added degassed toluene (8 mL). The mixture was then purged with argon again, the vial sealed, and heated for 1 h at 140° C. in the microwave, then a further 4 h at 135° C. The mixture was cooled, diluted with ethyl acetate and passed through a pad of celite/silica, washing with more ethyl acetate. The dark solution was concentrated in vacuo. The residue was purified by FCC, using 0-40percent DCM in EtOAc, to give the title compound (966 mg, 49percent). 1H NMR (300 MHz, CDCl3): 1.32 (9H, s), 2.24 (3H, s), 3.82 (2H, br s), 5.49 (1H, s), 6.45-6.52 (1H, m), 6.65-6.71 (1H, m), 6.85-6.91 (1H, m). |
49% | With trans-N,N'-dimethyl-1,2-cyclohexyldiamine; copper(l) iodide; potassium carbonate; In toluene; at 135 - 140℃; for 5.0h;Inert atmosphere; Microwave irradiation; Sealed tube; | 5-tert-Butyl-2H-pyrazol-3-ylamine (1.11 g, 8.00 mmol), potassium carbonate (2.32 g, 16.8 mmol), copper (I) iodide (0.076 g, 0.40 mmol), and 3-bromo-5- methylphenol (1.80 g, 9.60 mmol) were weighed into a large microwave vial. This was then purged with argon then trans-N,N-dimethylcyclohexane-l,2-diamine (0.25 mL, 1.60 mmol) added. To this mixture was then added degassed toluene (8 mL). The mixture was then purged with argon again, the vial sealed, and heated for 1 h at 140 °C in the microwave, then a further 4 h at 135 °C. The mixture was cooled, diluted with ethyl acetate and passed through a pad of celite/silica, washing with more ethyl acetate. The dark solution was concentrated in vacuo. The residue was purified by FCC, using 0-40percent DCM in EtOAc, to give the title compound (966 mg, 49percent). NMR (300 MHz, CDC13): 1.32 (9H, s), 2.24 (3H, s), 3.82 (2H, br s), 5.49 (1H, s), 6.45-6.52 (1H, m), 6.65-6.71 (1H, m), 6.85-6.91 (lH, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With copper(l) iodide; potassium carbonate; (1S,2S)-N,N'-dimethyl-1,2-diaminocyclohexane; In 5,5-dimethyl-1,3-cyclohexadiene; for 3h;Inert atmosphere; Reflux; | b. 2-(5-Amino-3-tert-butyl-[1,4']bipyrazolyl-1'-yl)-ethanol (Intermediate Gb) A solution of Intermediate Ga (9.36 g, 39.3 mmol) in xylene (40 mL) was purged with argon for 30 min. In a separate flask, a mixture of 3-tert-butyl-1H-pyrazole-5-amine (5.75 g, 41.3 mmol), copper iodide (375 mg, 1.97 mmol), trans-N,N-dimethylcyclohexane-1,2-diamine (1.12 g, 7.87 mmol) and potassium carbonate (11.4 g, 82.6 mmol) was de-gassed and purged with argon three times. The xylene solution was then added, via cannula to the flask and the resultant brown solution was heated at reflux for 3 h. The cooled solution was diluted with EtOAc (40 mL) and washed with saturated aqueous ammonia solution/water (1:1, 40 mL). The aqueous layer was extracted with EtOAc (40 mL) and the combined organics were washed with water (40 mL) and brine (40 mL), dried (Na2SO4), filtered and concentrated in vacuo to afford a solid. This was purified by FCC, using 4-7.5% MeOH in DCM to afford the title compound (6.01 g, 61%). LCMS (Method 1): Rt 1.84 min, m/z 250 [MH+]. |
61% | With trans-N,N'-dimethyl-1,2-cyclohexyldiamine; copper(l) iodide; potassium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene; for 3h;Inert atmosphere; Reflux; | A solution of Intermediate 6a (9.36 g, 39.3 mmol) in xylene (40 mL) was purged with Argon for 30 min. In a separate flask, a mixture of 3-tert- butyl-lH-pyrazole-5-amine (5.75 g, 41.3 mmol), copper iodide (375 mg, 1.97 mmol), trans-N,N-dimethylcyclohexane- l ,2-diamine (1.12 g, 7.87 mmol) and potassium carbonate (1 1.4 g, 82.6 mmol) was de-gassed and purged with Argon three times. The xylene solution was then added, via cannula to the flask and the resultant brown solution was heated at reflux for 3 h. The cooled solution was diluted with EtOAc (40 mL) and washed with saturated aqueous ammonia solution/water (1 : 1 , 40 mL). The aqueous layer was extracted with EtOAc (40 mL) and the combined organics were washed with water (40 mL) and brine (40 mL), dried (Na2SO4), filtered and concentrated in vacuo to afford a solid. This was purified by FCC, using 4-7.5% MeOH in DCM, to afford the title compound (6.01 g, 61 %). LCMS (Method 3): Rt 1.84 min, m/z 250 [MH+]. |
61% | With copper(l) iodide; potassium carbonate; (1S,2S)-N,N'-dimethyl-1,2-diaminocyclohexane; In 5,5-dimethyl-1,3-cyclohexadiene; for 3h;Inert atmosphere; Reflux; | A solution of Intermediate Ga (9.36 g, 39.3 mmol) in xylene (40 mL) was purged with argon for 30 min. In a separate flask, a mixture of 3-tert-butyl-lH- pyrazole-5-amine (5.75 g, 41.3 mmol), copper iodide (375 mg, 1.97 mmol), trans- N,N-dimethylcyclohexane-l ,2-diamine (1.12 g, 7.87 mmol) and potassium carbonate (1 1.4 g, 82.6 mmol) was de-gassed and purged with argon three times. The xylene solution was then added, via cannula to the flask and the resultant brown solution was heated at reflux for 3 h. The cooled solution was diluted with EtOAc (40 mL) and washed with saturated aqueous ammonia solution/water (1 : 1 , 40 mL). The aqueous layer was extracted with EtOAc (40 mL) and the combined organics were washed with water (40 mL) and brine (40 mL), dried (Na2S04), filtered and concentrated in vacuo to afford a solid. This was purified by FCC, using 4-7.5% MeOH in DCM to afford the title compound (6.01 g, 61 %). LCMS (Method 1): Rt 1.84 min, m/z 250 [MH+]. |
61% | With copper(l) iodide; potassium carbonate; trans-N,N'-dimethylcyclohexane-1,2-diamine; In 5,5-dimethyl-1,3-cyclohexadiene; for 3h;Inert atmosphere; Reflux; | A solution of Intermediate 6a (9.36 g, 39.3 mmol) in xylene (40 mL)was purged with Argon for 30 min. In a separate flask, a mixture of 3-tertbutyl-lH-pyrazole-5-amine (5.75 g, 4 1.3 mmol), copper iodide (375 mg, 1.97mmol), trans-N,N-dimethylcyclohexane-l,2-diamine ( 1.12 g, 7.87 mmol) andpotassium carbonate ( 11.4 g, 82.6 mmol) was de-gassed and purged with Argon three times. The xylene solution was then added, via cannula to theflask and the resultant brown solution was heated at reflux for 3 h. The cooledsolution was diluted with EtOAc (40 mL) and washed with saturated aqueousammonia solution/water ( 1:1, 40 mL). The aqueous layer was extracted withEtOAc (40 mL) and the combined organics were washed with water (40 mL)and brine (40 mL), dried (Na2SO4), filtered and concentrated in vacuo toafford a solid. This was purified by FCC, using 4-7.5% MeOH in DCM, toafford the title compound (6.01 g, 61%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
9%; 35% | In ethanol; at 20℃; | Synthesis of ethyl 2-(tert-butyl)-5-(4-fluorophenyl)pyrazolo[l,5-a]pyrimidine-7- carboxylate and ethyl 2-(tert-butyl)-7-(4-fluorophenyl)pyrazolo[l,5-a]pyrimidine-5- carboxylate: Ethyl 4-(4-fluorophenyl)-2,4-dioxobutanoate (17.85 g, 75 mmol) and 5- amino-3-tert-butylpyrazole (4) (10.44 g, 75 mmol) were dissolved in dry ethanol (250 mL). The reaction mixture was stirred at room temperature overnight, by which time the reaction was complete. The reaction mixture was evaporated to dryness, resulting in 27 g of crude regioisomer mixture, which was separated by column chromatography on silica gel with gradient elution from hexanes to 5% THF in hexanes. The first regioisomer (upper spot on TLC) was obtained as a yellow powder (3 g). It was recrystallized from ethanol-water mixture and resulted 2.4 g (9 %) of ethyl 2-(tert-butyl)-5-(4-fluorophenyl)pyrazolo[l,5- aJpyrimidine-7-carboxylate as yellow crystals. The second regioisomer (lower spot on TLC) was obtained as a yellow thick oil (12 g). It was crystallized with isopropyl ether, and 9 g (35 %) of ethyl 2-(tert-butyl)-7-(4-fluorophenyl)pyrazolo[l ,5-a] pyrimidine-5- carboxylate was obtained as a yellow crystalline powder. |
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