Structure of 375853-82-0
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CAS No. : | 375853-82-0 |
Formula : | C11H20BNO2 |
M.W : | 209.09 |
SMILES Code : | CC1(C)OB(OC1(C)C)C1=CCNCC1 |
MDL No. : | MFCD11506075 |
InChI Key : | AIPUNCFCQBDNDJ-UHFFFAOYSA-N |
Pubchem ID : | 21105461 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
100% | With hydrogenchloride In tert-butyl methyl ether at 20℃; | Method 3: General conditions for the deprotection of a 7V-Boc carbamate in the presence of a boronate ester: The boronate ester is dissolved in te/t-butylmethylether (0.4 M final ester concentration) after which point HCl (g) is bubbled in over the course of 15 min. The reaction is allowed to stir at room temperature for an additional hour after which point the solvent is removed under a stream of nitrogen to provide the desired HCl amine salt as a white solid in quantitative yield.; Example 2: Tetrahydropyridine 2 was prepared in 3 steps starting with the deprotection of 1 using Method 3. The resulting HCl amine salt was dissolved in dichloromethane (0.2 M). Benzyl chloroformate (1.2 equiv) was added followed by triethylamine (3.0 equiv). The reaction was allowed to stir at room temperature for 2h after which point it was diluted with IN HCl and extracted with excess dichloromethane. The organic layer was dried over MgSψ4 and concentrated to provide the desired carbamate in quantitative yield, which was converted directly to boronic acid 2 using Method 2. [M-H]- = 260.1 m/z. Activity: B |
100% | With hydrogenchloride In 1,4-dioxane at 20℃; for 4 h; | To a solution of tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)-5,6-dihydropyridine-1(2H)-carboxylate (5g, 16 mmol) in dioxane (10 mL) was added 4N HCl dioxane solution (24.2 mL, 97 mmol) at RT, and the reaction was stirred at RT for 4 h. The mixture was concentrated under reduced pressure to afford the title compound (4 g, yield 100percent) as a white solid.MS (ES+) C11H21BCINO2 requires: 209, found 210 [M+H]+. |
100% | With hydrogenchloride In ethyl acetate at 0 - 26℃; for 3 h; | Tert-butyl 4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1 (2H)- carboxylate (ARK PHARMA, 25 g, 80.851 mmol) was dissolved in 250 mL of EtOAc and HCI 4N in EtOAc (SYMAX FINE CHEMICALS, 250 mL) was added at 0 °C. The mixture was allowed to 26 °C and stirred for 3 h. The reaction mixture was evaporated under reduced pressure. The crude was washed with diethyl ether and filtered to give title compound (20 g, quantitative). NMR (400 MHz, DMSO-d6) δ ppm: 9.30 (br s, 2H), 6.40-6.30 (m, 1 H), 3.64- 3.52 (m, 2H), 3.15-3.00 (m, 2H), 2.34-2.22 (m, 2H), 1.21 (s, 12H). |
96% | With hydrogenchloride In 1,4-dioxane; dichloromethane at 20℃; | To tert-butyl 4-(4,4,5,5-tetramethyl- 1 ,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine- 1 -carboxylate 51 (3 g, 9.7 mmol) in dichloromethane (5 mL) was added hydrochloric acid in 1,4-dioxane (4 N, 5 mL). The reaction was stirred at room temperature overnight, then concentrated twice from toluene. The residue was washed with ethyl acetate and dried under vacuum to produce compound 52 as an HC1 salt (2.3 g, 96percent). The data from the lH NMR spectrum were consistent with the structure of the compound. |
90% | With hydrogenchloride In diethyl ether; tert-butyl methyl ether at 20℃; | tert-butyl 4-(4,4,5 ,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)-5 ,6-dihydropyridine- 1(2H)-carboxylate (2 g, 6.47 mmol) was suspended in MTBE (8.1 mL) and 2M HC1 in Et20 (24 mL). The reaction was stirred rt overnight, the white precipitate formed collected by filtration and washed with Et20 to give the title compound (1.434 g, 90 percent).UPLC-MS: 0.51 mm, 210.3 [M+H]+, method 9. |
90% | With hydrogenchloride In diethyl ether; tert-butyl methyl ether at 20℃; | tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (2 g, 6.47 mmol) was suspended in MTBE (8.1 mL) and 2M HCl in Et2O (24 mL). The reaction was stirred rt overnight, the white precipitate formed collected by filtration and washed with Et2O to give the title compound (1.434 g, 90percent).UPLC-MS: 0.51 min, 210.3 [M+H]+, method 9. |
8 g | With hydrogenchloride In dichloromethane; isopropyl alcohol for 12 h; | Step 1: 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridinium chloride Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (10 g) is dissolved in dichloromethane (100 mL) and 5 M HCl in isopropanol (120 mL) and stirred for 12 hours. The solvents are evaporated, the residue is redissolved in toluene and the solvent is again evaporated to give the title compound. Yield: 8 g; LC (method 11): tR=0.68 min; Mass spectrum (ESI+): m/z=210 [M+H]+. |
8 g | With hydrogenchloride In dichloromethane; isopropyl alcohol for 12 h; | Tert-butyl 4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1 (2H)- carboxylate (1 0 g) is d issolved in d ichloromethane (1 00 m L) and 5 M HCI in isopropanol (120 mL) and stirred for 12 hours. The solvents are evaporated, the residue is redissolved in toluene and the sollvent is again evaporated to give the title compound. Yield: 8 g; LC (method 1 1 ): tR = 0.68 min; Mass spectrum (EST): m/z = 210 [M+H]+. |
8 g | With hydrogenchloride In dichloromethane; isopropyl alcohol for 12 h; | Tert-butyl 4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1 (2H)- carboxylate (10 g) is dissolved in dichloromethane (100 mL) and 5 M HCI in isopropanol (120 mL) and stirred for 1 2 hours. The solvents are evaporated, the residue is redissolved in toluene and the sollvent is again evaporated to give the title compound. Yield: 8 g; LC (method 1 1 ): tR = 0.68 min; Mass spectrum (EST): m/z = 210 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; at 80℃; for 18h; | A solution of <strong>[1532-71-4]1-<strong>[1532-71-4]bromoisoquinoline</strong></strong> (0.35 g, 1.68 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate (US 2004/0186103) (0.5 g, 1.68 mmol), dichloro(1,1-bis(diphenylphosphino)ferrocene)palladium(II) (0.065 g, 0.05 mol equiv.) and potassium carbonate (0.66 g, 5.0 mmol) in 1,2-dimethoxyethane (10 mL) was heated at 80 °C for 18 hours. The reaction mixture was allowed to cool and then evaporated under reduced pressure. The residue was purified' by column chromatography on silica gel eluting with ethyl acetate: pentane 50 : 50 to afford the title compound as a pale yellow oil, 0.14 g. LRMS (APCI+): m/z [M+H]+ 311 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; water; at 100℃;Product distribution / selectivity; | te^-ButyI4-(4-chloro-7Jy-pyrrolo[2,3-«qpyrimidm-6-yl)-3,6-dihydropyridine-l(2fl)-carboxylate (compound of Formula VIII-Boc).; IXMKCn[228] To a suspension of <strong>[876343-10-1]4-chloro-6-iodo-7H-pyrrolo[2,3-d]pyrimidine</strong> (5.0g,O.OlSmol) in 1,4-dioxane (120mL) and water (30mL) were added 4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-l-carboxylic acid tert-butyl ester (5.97g,0.0193mol), potassium carbonate (4.9g, 0.036mol) and PdCl2(dppf)-CH2Cl2 (0.73g,0.89mmol). The flask was evacuated and refilled with N2 (3x). The mixture was heated at100C overnight. LC-MS showed the reaction was complete. The mixture was diluted withethyl acetate (200mL), then washed with brine (2x50mL), and dried over anhydrous sodiumsulfate. The filtrate was concentrated under reduced pressure to wlOOmL, the resulting whiteprecipitate was collected by filtration to give the first batch of the title compound. The filtratewas concentrated and the residue was purified by chromatography on silica gel, eluting withHex:EtOAc = 70:30 -> 50:50 to give a white solid (containing pinacol), which was furthercrystallized with EtOAc/hexanes to give the second batch of the title compound as a whitesolid. LC-MS (ES, Pos.): 335/337 (3/1) [MH+]. 'H NMR (CDC13,400 MHz): 5 = 1.51 (s,9H), 2.61 (m, 2H), 3.70 (m, 2H), 4.20 (m, 2H), 6.27 (s, 1H), 6.55 (s, 1H), 8.61 (s, 1H), 10.3(brs, 1H). | |
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In propan-1-ol; water; at 100℃; for 18h; | 4-(4-(5-Fluoro-3-r4-(1-fluoro-cvclopropyl)-benzoylaminol-2-methyl-phenyl)-7H- Pyrrolor2 -dlpyrimidin-6-yl)-3,6-dihvdro-2H-pyridine-1-carboxylic acid dimethylamide(1 ) 4-(4-Chloro-7H-pyrrolor2,3-dlpyrimidin-6-yl)-3,6-dihvdro-2H-pyridine-1-carboxylic acid tert-butyl ester, Intermediate 1To a mixture of <strong>[876343-10-1]4-chloro-6-iodo-7H-pyrrolo[2,3-d]pyrimidine</strong> (2.6 g, 9.30 mmol) and dichlorobis(triphenylphosphine)palladium (II) (0.52 g, 0.74 mmol) in 1-propanol (120 ml) and aqueous sodium carbonate solution (2M, 10.23 ml, 20.46 mmol), 4-(4, 4,5,5- tetramethyl-[1 ,2,3]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (3.02 g, 9.77 mmol) was added. The mixture was heated to 100C for 18 hours. After cooling the brownish mixture was diluted with 200 ml water and extracted with DCM. The organic layer was washed with brine (2x) and dried over sodium sulfate, than filtered and evaporated. The residue was purified by flash chromatography on silica (cyclohexane/EtOAc 1 :1 ) to afford the compound Intermediate 1 as a beige solid.MS (ESI): 335 [M+H]+ , 1H-NMR (DMSO-d6): delta (ppm) 12.64 (br s, 1 H), 8.56 (s, 1 H), 6.59 (s, 2H), 4.08 (br s, 2H), 3.57 (m, 2H), 2.55 (m, 2H), 1.45 (s, 9H). (2) 4-Chloro-6-(1.2.3.6-tetrahvdro-pyridin-4-vn-7H-pyrrolor2.3-dlpyrimidine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With hydrogenchloride; In tert-butyl methyl ether; at 20℃; | Method 3: General conditions for the deprotection of a 7V-Boc carbamate in the presence of a boronate ester: The boronate ester is dissolved in te/t-butylmethylether (0.4 M final ester concentration) after which point HCl (g) is bubbled in over the course of 15 min. The reaction is allowed to stir at room temperature for an additional hour after which point the solvent is removed under a stream of nitrogen to provide the desired HCl amine salt as a white solid in quantitative yield.; Example 2: Tetrahydropyridine 2 was prepared in 3 steps starting with the deprotection of 1 using Method 3. The resulting HCl amine salt was dissolved in dichloromethane (0.2 M). Benzyl chloroformate (1.2 equiv) was added followed by triethylamine (3.0 equiv). The reaction was allowed to stir at room temperature for 2h after which point it was diluted with IN HCl and extracted with excess dichloromethane. The organic layer was dried over MgSpsi4 and concentrated to provide the desired carbamate in quantitative yield, which was converted directly to boronic acid 2 using Method 2. [M-H]- = 260.1 m/z. Activity: B |
100% | With hydrogenchloride; In 1,4-dioxane; at 20℃; for 4h; | To a solution of tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)-5,6-dihydropyridine-1(2H)-carboxylate (5g, 16 mmol) in dioxane (10 mL) was added 4N HCl dioxane solution (24.2 mL, 97 mmol) at RT, and the reaction was stirred at RT for 4 h. The mixture was concentrated under reduced pressure to afford the title compound (4 g, yield 100percent) as a white solid.MS (ES+) C11H21BCINO2 requires: 209, found 210 [M+H]+. |
100% | With hydrogenchloride; In ethyl acetate; at 0 - 26℃; for 3h; | Tert-butyl 4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1 (2H)- carboxylate (ARK PHARMA, 25 g, 80.851 mmol) was dissolved in 250 mL of EtOAc and HCI 4N in EtOAc (SYMAX FINE CHEMICALS, 250 mL) was added at 0 °C. The mixture was allowed to 26 °C and stirred for 3 h. The reaction mixture was evaporated under reduced pressure. The crude was washed with diethyl ether and filtered to give title compound (20 g, quantitative). NMR (400 MHz, DMSO-d6) delta ppm: 9.30 (br s, 2H), 6.40-6.30 (m, 1 H), 3.64- 3.52 (m, 2H), 3.15-3.00 (m, 2H), 2.34-2.22 (m, 2H), 1.21 (s, 12H). |
96% | With hydrogenchloride; In 1,4-dioxane; dichloromethane; at 20℃; | To tert-butyl 4-(4,4,5,5-tetramethyl- 1 ,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine- 1 -carboxylate 51 (3 g, 9.7 mmol) in dichloromethane (5 mL) was added hydrochloric acid in 1,4-dioxane (4 N, 5 mL). The reaction was stirred at room temperature overnight, then concentrated twice from toluene. The residue was washed with ethyl acetate and dried under vacuum to produce compound 52 as an HC1 salt (2.3 g, 96percent). The data from the lH NMR spectrum were consistent with the structure of the compound. |
90% | With hydrogenchloride; In diethyl ether; tert-butyl methyl ether; at 20℃; | tert-butyl 4-(4,4,5 ,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)-5 ,6-dihydropyridine- 1(2H)-carboxylate (2 g, 6.47 mmol) was suspended in MTBE (8.1 mL) and 2M HC1 in Et20 (24 mL). The reaction was stirred rt overnight, the white precipitate formed collected by filtration and washed with Et20 to give the title compound (1.434 g, 90 percent).UPLC-MS: 0.51 mm, 210.3 [M+H]+, method 9. |
90% | With hydrogenchloride; In diethyl ether; tert-butyl methyl ether; at 20℃; | tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (2 g, 6.47 mmol) was suspended in MTBE (8.1 mL) and 2M HCl in Et2O (24 mL). The reaction was stirred rt overnight, the white precipitate formed collected by filtration and washed with Et2O to give the title compound (1.434 g, 90percent).UPLC-MS: 0.51 min, 210.3 [M+H]+, method 9. |
With hydrogenchloride; In methanol; at 20℃; for 1h; | The mixture of tert-butyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-5,6- dihydropyridine-l(2H)-carboxylate (4.0 g, 12.9 mmol) in HCl/MeOH (20 mL) was stirred at room temperature for lhour. Then it was concentrated to give 4-(4,4,5,5-Tetramethyl- [l,3,2]dioxaborolan-2-yl)-l,2,3,6-tetrahydro-pyridine hydyochloride (2.9 g, 11.8mmol, yield:91.4percent)which was used in the next step without further purification. ESI-MS (M+1): 210 calc. for CnH2oBN02 209 | |
8 g | With hydrogenchloride; In dichloromethane; isopropyl alcohol; for 12h; | Step 1: 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridinium chloride Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (10 g) is dissolved in dichloromethane (100 mL) and 5 M HCl in isopropanol (120 mL) and stirred for 12 hours. The solvents are evaporated, the residue is redissolved in toluene and the solvent is again evaporated to give the title compound. Yield: 8 g; LC (method 11): tR=0.68 min; Mass spectrum (ESI+): m/z=210 [M+H]+. |
8 g | With hydrogenchloride; In dichloromethane; isopropyl alcohol; for 12h; | Tert-butyl 4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1 (2H)- carboxylate (1 0 g) is d issolved in d ichloromethane (1 00 m L) and 5 M HCI in isopropanol (120 mL) and stirred for 12 hours. The solvents are evaporated, the residue is redissolved in toluene and the sollvent is again evaporated to give the title compound. Yield: 8 g; LC (method 1 1 ): tR = 0.68 min; Mass spectrum (EST): m/z = 210 [M+H]+. |
8 g | With hydrogenchloride; In dichloromethane; isopropyl alcohol; for 12h; | Tert-butyl 4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1 (2H)- carboxylate (10 g) is dissolved in dichloromethane (100 mL) and 5 M HCI in isopropanol (120 mL) and stirred for 1 2 hours. The solvents are evaporated, the residue is redissolved in toluene and the sollvent is again evaporated to give the title compound. Yield: 8 g; LC (method 1 1 ): tR = 0.68 min; Mass spectrum (EST): m/z = 210 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.8% | With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate; at 120℃; for 5h; | Mix l-bromo-3-nitro-5-(trifluoromethyl)benzene (200 mg, 0.65 mmol), tert-butyl 4-(4,4,5,5-tetramemyl-l,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-l(2H)-carboxylate (175 mg, 0.65 mmol), tetrakis(triphenylphosphine)palladium(0) (35 mg, 0.03 mmol) in dioxane and saturated sodium bicarbonate solution (3:1, 10 mL), stir the mixture at 120C for 1.5 hrs. Cool to room temperature; concentrate under reduced pressure to give the crude product. Purify by flash chromatography (silica gel, EtOAc:PE=20:l) to afford the product as a yellow solid (310 mg, 82.8%). MS: (M+23): 395.2 |
82.8% | With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate; In 1,4-dioxane; at 120℃; for 1.5h; | Mix <strong>[630125-49-4]1-bromo-3-nitro-5-(trifluoromethyl)benzene</strong> (200 mg, 0.65 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1 (2H)-carboxylate (175 mg, 0.65 mmol), tetrakis(triphenylphosphine)palladium(0) (35 mg, 0.03 mmol) in dioxane and saturated sodium bicarbonate solution (3:1, 10 mL), stir the mixture at 120 C. for 1.5 hrs. Cool to room temperature; concentrate under reduced pressure to give the crude product. Purify by flash chromatography (silica gel, EtOAc:PE=20:1) to afford the product as a yellow solid (310 mg, 82.8%). MS: (M+23): 395.2. |
47% | With potassium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 80℃; | fert-Butyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine- 1 (2H)-carboxylate (200 mg, 0.646 mmol), l-bromo-3-nitro-5-(trifluoromethyl)benzene (261 mg, 0.969 mmol), Pd(dppf 2Ci2 dichloromethane adduct (52 mg, 0.064 mmol) and potassium carbonate (268 mg, 1.94 mmol) were suspended in anhydrous N,N-dimethylformamide (5 mL). The mixture was stirred at 80 C overnight and then was cooled to room temperature. The mixture was partitioned between ethyl acetate and water. The organic layer was dried over magnesium sulfate, was filtered and was concentrated. The residue was purified by column chromatography (eluted with ethyl acetate:Hexanes = 1 : 10) to give tert-butyl 4-[3- nitro-5-(trifluoromethyl)phenyl]-3,6-dihydropyridine-l(2H)-carboxylate (1 14 mg, 47% yield) as a yellow sticky oil. XH NMR (400 MHz, CDC13): delta 8.37 (s, 1H), 8.33 (s, 1H), 7.89 (s, 1H), 6.27 (s, 1H), 4.09 (s, 2H), 3.65 (t, 2H), 2.55 (s, 2H), 1.46 (s, 9H). |
891 mg | With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate; In 1,4-dioxane; at 120℃; for 6h; | To a solution of <strong>[630125-49-4]1-bromo-3-nitro-5-(trifluoromethyl)benzene</strong> (1.0 g, 3.70 mmol) in 1,4-dioxane (35 mL) were added tert-butyl 4-(4,4,5 ,5 -tetramethyl- 1,3 ,2-dioxaborolan-2-yl)-5 ,6-dihydropyridine-1(2H)-carboxylate (1.1 g, 3.70 mmol),tetrakis(triphenylphosphine)palladium(0) (213 mg, 0.18 mmol) and saturated aqueous sodium bicarbonate solution (15 mL) and the mixture was heated at 120 C for 6 h. The mixture was cooled to RT and diluted with ethyl acetate. The organic layer was washed with water followed by brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue obtained was purified by silica gel column chromatography to yield 891 mg of thedesired compound. ?H NMR (400 MHz, DMSO-d6) oe 1.52 (s, 9H), 2.60 (br s, 2H), 3.71 (t, J= 5.6 Hz, 2H), 4.18 (br s, 2H), 6.32 (br s, 1H), 7.94 (s, 1H), 8.39 (s, 1H), 8.42 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 90℃; for 10h; | 1.2 e-Amino-S-cyano-S'.e'-dihydro^'H-tS^'jbipyridinyM '-carboxylic acid tert- butyl ester To a solution of <strong>[709652-82-4]2-amino-5-bromo-nicotinonitrile</strong> (0.60 g; 3.02 mmol) in dioxane (24 mL) and water (6 mL) 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan- 2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (1.04 g; 3.32 mmol) and Na2CO3 (0.98 g; 9.05 mmol) were added and the mixture was degassed for 30 min. 1 ,1'-Bis(diphenylphosphino)ferrocene]dichloro- palladium(ll) complex with dichloromethane (0.13 g; 0.15 mmol) was added and the reaction mixture was heated to 90 C for 10 h. The reaction mixture was cooled to ambient temperature, filtered through celite and the solvent was concentrated under reduced pressure. The residue was purified by flash column chromatography using petrol ether and ethyl acetate (5:5) to afford the title compound (450.0 mg; 50%) as a pale-yellow solid; 1H NMR (400 MHz, DMSO-d6) delta 8.32 (d, J = 2.5 Hz, 1H), 7.92 (d, J = 2.5 Hz, 1H), 6.92 (s, 2H), 6.08 (s, 1H), 3.94 (s, 2H), 3.49 (t, J = 5.6 Hz, 2H), 2.37 (d, J = 1.5 Hz, 2H), 1.40 (s, 9H); LC/MS (B), Rt: 3.50 min; (M+H) 301.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With tetrakis(triphenylphosphine) palladium(0); cesium fluoride; In methanol; 1,2-dimethoxyethane; at 100.0℃; for 5h;Inert atmosphere; | tert-Butyl 4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1 (2H)-carboxylate (2.0 g, 6.55 mmol), 2-bromo-1,5-dimethyl-IH-imidazole (1.13 g, 6.45 mmol) and CsF (2.9 g,1.85 mmol) were dissolved in DME: MeCH (2:1, 30 mL). The reaction mixture was degassed for 5 mins, then Pd(PPh3)4 (73 mg, 0.064 mmol) was added and the resulting reaction mixture was stirred for 5 h at 100C. The reaction mixture was partitioned between H20 (100 mL) andEtOAc (100 mL), the aqueous layer was further extracted with EtOAc (2 x 100 mL), the organic layers were combined, dried (Na2SO4) and the solvents were removed in vacuo. The residue was purified by column chromatography (normal silica, mesh size: 60-120, 13% to 17% Ethyl acetate in Hexane) to give tert-butyl 4-(1 ,5-dimethyl-1 H-imidazol-2-yl)-3,6-dihydropyridine- 1(2H)-carboxylate (1 g, 55%) as a yellow gum.LCMS (Method F): m/z 278 (M+H) (ES), at 1.70 mm, UV active |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In 1,4-dioxane; water; at 90℃;Inert atmosphere; | Into a 250~mL 3-necked round-bottom flask purged and maintained under nitrogen, were placed a solution of methyl 3~bromo~1 H-indazole-5- carboxylate (5 g, 19.6 mmol) in 1 ,4-dioxane (210 mL), tert-butyl 4-(tetramethyl- 1 ,3,2-dioxaborolan-2-yl)-1 ,2,3,6- tetrahydropyridine-1-carboxyiate (9.2 g, 29.7 mmol), Pd(OAc)2 (442 mg, 1.97 mmol), S-Phos (1.62 g, 3.94 mmol) and a solution of K3PO4 (16.72 g, 78.77 mmol) in water(31 mL). The resulting mixture was stirred overnight at 90C in an oil bath, and then concentrated under vacuum. The residue was purified on a silica gel column eluted with ethyl acetate/petroleum ether (0:100-1 : 1 ) to yield methyl 3-[1-[(tert-butoxy)carbonyl]- 1 ,2,3,8-tetrahydropyridin-4-yl]-1 H-indazole-5-carboxylate as a white solid. LC/MS (ES, m/z): 358 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 80℃;Inert atmosphere; | A 50-mL round-bottom flask was charged with 3-bromo-4- (trifluoromethyl)benzaldehyde (1 .00 g, 3.95 mmol, 1.00 equiv), tert-butyl 4-(tetramethyl- 1,3,2- dioxaborolan-2-yl)- 1,2,3 ,6-tetrahydropyridine- 1 -carboxylate (1.84 g, 5.95 mmol, 1.50 equiv), tetrakis(triphenylphosphine)palladium (230 mg, 0.198 mmol, 0.05 equiv), potassium carbonate (1.64 g, 11.9 mmol, 3.00 equiv), 1,4-dioxane (10 mL), and water (2 mL) under nitrogen. The resulting solution was stirred overnight at 80 C and quenched with water (10 mL). The mixture was extracted with dichloromethane (3 x 10 mL) and the organic layers were combined, washed with brine (2 x 10 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (1/4) to provide 1.00 g (71% yield) of tert-butyl 4-(5-formyl-2- (trifluoromethyl)phenyl)-3 , 6-dihydropyridine- 1 (2H)-carboxylate as yell ow oil. LCMS (ESI, m/z): 356 [M+H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 110℃; for 0.5h;Microwave irradiation; Inert atmosphere; | The compound 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester14a (1.64 g, 5.3 mmol), <strong>[661463-17-8]4-bromo-6-fluoroquinoline</strong> (1 g, 4.4 mmol), tetrakis(triphenylphosphine)palladium (508 mg, 0.44 mmol), potassium carbonate (1.22 g, 8.8 mmol), water (2 ml) and 1,4-dioxane (10 ml) were mixed, and then heated in a microwave reactor at 110 C for 30 minutes under a nitrogen atmosphere. After cooling to room temperature, it was filtered, and the filtrate was evaporated under reduced pressure. To give the desired product 4-(6-fluoroquinolin-4-yl)-3,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester 14b (2g, crude).This product was used directly in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; water; at 120℃; for 0.75h;Sealed tube; Inert atmosphere; Microwave irradiation; | General procedure: The boronic acid pinacol ester (1 equiv.), aryl halide (1 equiv.) and Pd(dppf)Cl2·CH2Cl2 adduct (0.1 equiv.) were dissolved in a mixture of DME and aqueous sodium carbonate (1M) in a microwave vial. The vial was sealed, evacuated and backfilled with N2. The reaction mixture was heated in the microwave at 120C for 45min and monitored by LCMS. The reaction mixture was concentrated in vacuo to give the crude material which was purified by Biotage column chromatography (see individual compounds for details of the eluent used). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; water; at 120℃; for 0.75h;Sealed tube; Inert atmosphere; Microwave irradiation; | General procedure: The boronic acid pinacol ester (1 equiv.), aryl halide (1 equiv.) and Pd(dppf)Cl2·CH2Cl2 adduct (0.1 equiv.) were dissolved in a mixture of DME and aqueous sodium carbonate (1M) in a microwave vial. The vial was sealed, evacuated and backfilled with N2. The reaction mixture was heated in the microwave at 120°C for 45min and monitored by LCMS. The reaction mixture was concentrated in vacuo to give the crude material which was purified by Biotage column chromatography (see individual compounds for details of the eluent used). |
Tags: 375853-82-0 synthesis path| 375853-82-0 SDS| 375853-82-0 COA| 375853-82-0 purity| 375853-82-0 application| 375853-82-0 NMR| 375853-82-0 COA| 375853-82-0 structure
A292351 [454482-11-2]
1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine
Similarity: 0.98
A219175 [1121057-75-7]
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine hydrochloride
Similarity: 0.98
A497429 [1627158-64-8]
1-Ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine
Similarity: 0.98
A133137 [1462950-92-0]
1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine hydrochloride
Similarity: 0.97
A932544 [1642583-50-3]
1-Isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine
Similarity: 0.96
A292351 [454482-11-2]
1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine
Similarity: 0.98
A219175 [1121057-75-7]
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine hydrochloride
Similarity: 0.98
A497429 [1627158-64-8]
1-Ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine
Similarity: 0.98
A133137 [1462950-92-0]
1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine hydrochloride
Similarity: 0.97
A932544 [1642583-50-3]
1-Isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine
Similarity: 0.96
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