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CAS No. : | 113451-59-5 | MDL No. : | MFCD01569250 |
Formula : | C10H18N2O2 | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | UXAWXZDXVOYLII-YUMQZZPRSA-N |
M.W : | 198.26 | Pubchem ID : | 11521263 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H315-H319-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 |
---|---|---|
66% | With cesium fluoride; In dimethyl sulfoxide; at 120℃; for 18h; | Step : 1 Preparation of tert-butyl (1S,4S)-5-(4-(trifluoromethyl)pyridin-2-yl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate [Show Image] <strong>[175205-81-9]2-bromo-4-(trifluoromethyl)pyridine</strong> (0.5 g, 2.21 mmol), cesium fluoride (0.33 g, 2.21 mmol) and tert-butyl (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (1.3 g, 6.63 mmol) were added in DMSO (5 mL). The reaction was then heated to 120°C for 18 hours. The reaction mass was diluted with water and extracted with DCM (3 X 100 mL). The organic layer was washed with water, brine solution, dried over anhydrous MgSO4 and concentrated to get the crude product which was dissolved in DCM. The title intermediate was precipitated by the addition of n-hexane as an off white solid (0.4 g, 66 percent). 1HNMR (DMSO-d6, 400 MHz): delta 8.27 (s, 1 H), 6.82-6.83 (m, 2H), 4.91 (s, 1 H), 4.42-4.52 (m, 1 H), 3.84 (s, 1 H), 3.36-3.59 (m, 1 H), 3.34-3.34 (m, 1 H), 3.14-3.16 (m, 1 H), 1.89 (s, 2H), 1.36 (s, 9H). LCMS (Method D): Mass found (M+ 344.0), Rt (min): 3.58, Area (percent) 97.2 (Max), 98.9 (254 nm). |
With cesium fluoride; In dimethyl sulfoxide; at 120℃; for 18h; | Step : 1 Preparation of tert-butyl (1S,4S)-5-[4-(trifluoromethyl)pyridin-2-yl]-2,5- diazabicyclo[2.2.1 ]heptane-2-carboxylate<strong>[175205-81-9]2-bromo-4-(trifluoromethyl)pyridine</strong> (0.5 g, 2.21 mmol), cesium fluoride (0.33 g, 2.21 mmol) and tert-butyl (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (1.3 g, 6.63 mmol) were added in DMSO (5 ml_). The reaction was then heated to 120°C for 18 hours. The reaction mass was diluted with water and extracted with DCM (3 X 100 mL). The organic layer was washed with water, brine solution, dried over anhydrous MgS04 and concentrated to get the crude product which was dissolved in DCM. The title intermediate was precipitated by the addition of n-hexane as an off white solid (0.4 g, 66 percent). HNMR (DMSO-d6, 400 MHz): delta 8.27 (s, 1 H), 6.82-6.83 (m, 2H), 4.91 (s, 1 H), 4.42-4.52 (m, 1 H), 3.84 (s, 1 H), 3.36-3.59 (m, 1 H), 3.34-3.34 (m, 1 H), 3.14-3.16 (m, 1 H), 1.89 (s, 2H), 1.36 (s, 9H). LCMS (Method D): Mass found (M+ 344.0), Rt (min): 3.58, Area (percent) 97.2 (Max), 98.9 (254 nm). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium carbonate; In N,N-dimethyl-formamide; at 50℃; for 24h;Inert atmosphere; | A suspension of 1?fluoro?2?methoxy?4?nitrobenzene (2.59 g, 15.13 mmol), (1S,4S)?tert?butyl 2,5? diazabicyclo[2.2.1]heptane?2?carboxylate (3.00 g, 15.13mmol) and potassium carbonate (3.14 g, 22.7 mmol) in anhydrous DMF (40 mL) was heated to 50 °C under a nitrogen atmosphere for 24 hours. The reaction mixture was allowed to cool to room temperature, diluted with water (120 mL) and stirred at room temperature for 15 minutes. The precipitated solid was isolated byfiltration and dried under vacuum to give the title compound as a yellow solid (4.49 g, 85percent) . LCMS (MethodC): = 1.44 mm, m/z = 294 [M_tBu+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
840 mg | With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In toluene; at 45℃; for 4h; | General procedure: To a solution of di-tert-butyl (3-bromo-5-(trifluoromethyl)phenyl)imidodicarbonate (step 1 intermediate) (2.2 g, 4.89 mmol) in 1,4-dioxane (20 mL) were added N,N,N?25 trimethylethylenediamine (636 jiL, 4.89 mmol), sodium tert-butoxide (1.40 g, 14.7 mmol),tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3) (447 mg, 0.49 mmol) and (2- biphenyl)di-tert-butylphosphinetriethylamine (JohnPhos) (37 mg, 1 .47mmol) at RT and the reaction mixture was stirred at 45 C for 4 h. The mixture was cooled to RT and filteredthrough celite. The filtrate was concentrated and the residue was dissolved in ethyl acetate. The organic solution was washed with 0.1 N HC1 followed by water, dried over anhydrous sodium sulfate, filtered and concentrated. The residue obtained was purified by silica gel column chromatography to yield 2.01 g of the desired compound. The compound was as suchcarried forward to the next step without characterization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 2h; | To a flask were added (1S, 4S) -tert-butyl 2, 5-diazabicyclo [2.2.1] heptane-2-carboxylate (3.0 g, 15.13 mmol) (1-b) , 2, 4-dichloropyrimidine-5-carbonitrile (3.30 g, 18.97 mmol, commercially available from Ark Pharm, Inc., Libertyville, IL, USA) (1-a) , DMF (100 ml) and DIPEA (8 ml, 45.8 mmol) . The mixture was stirred at RT for 2 h, after which the solvent was removed in vacuo. The residue was dissolved into DCM and purified by column chromatography (silica gel, eluting with DCM) to afford tert-butyl (1S, 4S) -5- (2-chloro-5-cyanopyrimidin-4-yl) -2, 5-diazabicyclo [2.2.1] heptane-2-carboxylate (1-c) . MS (ESI) Calc?d for C15H19ClN5O2[M+H]+, 336; found, 336. |
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