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CAS No. : | 25271-35-6 | MDL No. : | MFCD01570459 |
Formula : | C7H14ClNO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | HENMKHNMVUDRMJ-UHFFFAOYSA-N |
M.W : | 179.65 | Pubchem ID : | 2778261 |
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 |
---|---|---|
In a 3 necked flask under an atmosphere, of nitrogen, <strong>[25271-35-6]N-methylpiperidine-2-carboxylic acid hydrochloride</strong> (1.79g, 10.0 mmol), HOBt (1.35g, 10 mmol). EDC hydrochloride (1.92g, 10 mmol) and TEA (3.0Og, 30mmol) were dissolved in CH2Cl2 (100 mL, dry) at 0C. After 30 min, diphenylpropylamine (2.11g, 10 mmol) was added. After 1 more hour stirring at 0C, the mixture was allowed to stir at rt overnight. When TLC showed consumption of (nearly) all starting materials, the reaction mixture was quenched with water (150 mL). The layers were separated and the organic layer was washed with NaHCO3 (50 mL, sat.), dried (MgSO4), filtered and concentrated in vacuo to yield a yellow/orange oil (4.12g). This crude oil was purifierd by chromatography (Silica, CH2C12/CH3OH, gradient 0-3%) to yield a colorless oil (2.6g, 7.7 mmol). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step A: A mixture of 1-methylpiperidine-2-carboxylic acid hydrochloride (0.57 g, 3.17 mmol), <strong>[17672-21-8]methyl 2-amino-3-hydroxybenzoate</strong> (0.64 g, 3.80 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.26 g, 6.34 mmol), 1-hydroxybenzotriazole (0.85 g, 6.34 mmol) and DMF (20 mL) was stirred at room temperature for 5 min, then diisopropylethylamine (1.46 mL, 8.88 mmol) was added. The resulting reaction mixture was stirred at room temperature for 17 h. The mixture was diluted with ethyl acetate (10 mL), and then washed with saturated sodium bicarbonate (10 mL). The aqueous phase was further extracted with ethyl acetate (3×40 mL). The combined organic phase was washed with brine (10 mL), dried (Na2SO4), filtered and concentrated. The crude product (a mixture of 2-amino-3-(methoxycarbonyl)phenyl 1-methylpiperidine-2-carboxylate and methyl 3-hydroxy-2-(1-methylpiperidine-2-carboxamido)benzoate) was directly elaborated in step B: MS (ESI+) m/z 293 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; In dichloromethane; at 20℃; | A mixture of 1-methyl-6-(4-(3-(methylamino)propoxy)-3-(trifluoromethyl)phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile (50mg), triethylamine (71 mul_), <strong>[25271-35-6]1-methylpiperidine-2-carboxylic acid hydrochloride</strong> (17mg), and O- benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate (58mg) in DCM (1.5ml) was stirred overnight at room temperature. The mixture was washed with sodium bicarbonate and then purified by prep HPLC (acidic) to give the expected product (1 1 mg). 1H NMR (CD3OD) delta: 8.29-8.52 (m, 4H), 7.27-7.40 (m, 1 H), 4.16-4.36 (m, 2H), 4.06 (s, 3H), 3.58-3.92 (m, 2H), 2.86-3.27 (m, 5H), 2.14-2.37 (m, 6H), 1.26- 1.90 (m, 6H). MS m/z 515 (M + H). | |
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; In dichloromethane; at 20℃; | B: N-(3-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)propyl)-N,1-dimethylpiperidine-2-carboxamideA mixture of 1-methyl-6-(4-(3-(methylamino)propoxy)-3-(trifluoromethyl)phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile (50 mg), triethylamine (71 muL), <strong>[25271-35-6]1-methylpiperidine-2-carboxylic acid hydrochloride</strong> (17 mg), and O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate (58 mg) in DCM (1.5 ml) was stirred overnight at room temperature. The mixture was washed with sodium bicarbonate and then purified by prep HPLC (acidic) to give the expected product (11 mg). NMR (CD3OD) delta: 8.29-8.52 (m, 4H), 7.27-7.40 (m, 1H), 4.16-4.36 (m, 2H), 4.06 (s, 3H), 3.58-3.92 (m, 2H), 2.86-3.27 (m, 5H), 2.14-2.37 (m, 6H), 1.26-1.90 (m, 6H). MS m/z 515 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Method 26Synthesis of 5-(4-{l-r5-(l-Methyl-piperidin-2-yl)-ri,2,41oxadiazol-3-yll-cvclobutyl}- phenyl)-pyrimidin-2-ylamine (Example 281)I-2.5 R89 Ex 281To a suspension of R89 (190 mg, 1.06 mmol) in dioxane (10 ml) is added DIEA (0.18 ml, 1.06 mmol) and CDI (172 mg, 1.06 mmol) at room temperature. The mixture is stirred at 50 C for 30 minutes. After this time 1-2.5 (200 mg, 0.71 mmol) is added and the resulting mixture is heated at 100C for 20 hours. After this time the reaction is concentrated and the remaining residue is purified via column chromatography (25g silica gel, 0-5% MeOH/DCM). The product-containing fractions are combined and concentrated to give the title compound (140 mg) m/z 391.4 [M+l] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | DCM under nitrogen TEA (5.12 g, 50.6 mmol, 4.4 eq) was added to <strong>[25271-35-6]1-methylpiperidine-2-carboxylic acid hydrochloride</strong> (2.27 g, 12.65 mmol, 1.1 eq) contained in methanol (46 mL, c = 0.25) The mixture was stirred at room temperature for 30 minutes. The mixture was cooled to 0 C in an ice bath, and then ClCO2Et was slowly added dropwise over 20 minutes. To this mixture was added dropwise 3 (1.6 g, 11.5 mmol, 1.0 eq) in DCM (2 mL) and stirred overnight. The residue after rotary evaporation was purified by column chromatography to give the desired product 4 (0.5 g, 16% yield). |
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