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CAS No. : | 371764-64-6 | MDL No. : | MFCD03095174 |
Formula : | C9H8BNO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | KATIRQRAVXTBNY-UHFFFAOYSA-N |
M.W : | 172.98 | Pubchem ID : | 2762748 |
Synonyms : |
|
Num. heavy atoms : | 13 |
Num. arom. heavy atoms : | 10 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 3.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 51.57 |
TPSA : | 53.35 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.58 cm/s |
Log Po/w (iLOGP) : | 0.0 |
Log Po/w (XLOGP3) : | 1.09 |
Log Po/w (WLOGP) : | -0.09 |
Log Po/w (MLOGP) : | 0.04 |
Log Po/w (SILICOS-IT) : | -0.17 |
Consensus Log Po/w : | 0.17 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.1 |
Solubility : | 1.37 mg/ml ; 0.0079 mol/l |
Class : | Soluble |
Log S (Ali) : | -1.8 |
Solubility : | 2.72 mg/ml ; 0.0158 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -2.59 |
Solubility : | 0.448 mg/ml ; 0.00259 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.66 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H332-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 |
---|---|---|
EXAMPLE 19B 4-quinolinylboronic acid The desired product was prepared by substituting Example 19A for Example 43A in Example 43B. 1H NMR (300 MHz, DMSO-d6) delta 8.86 (d, 1H), 8.75 (s, 1H), 8.25 (dd, 1H), 8.25 (dd, 1H), 8.00 (dd, 1H), 7.76-7.70 (m, 1H), 7.62-7.56 (m, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With potassium phosphate;tris-(dibenzylideneacetone)dipalladium(0); XPhos; In butan-1-ol; at 150℃; for 0.25h;Inert atmosphere; Microwave irradiation; | A microwave reaction vial was charged with 17a (240 mg, 0.52 mmol), 4- quinoline boronic acid (135 mg, 0.78 mmol), Pd2(dba)3 ( 18 mg), 2- dicyclohexylphosphino-2',4',6'-triisopropylbiphcnyl ( 18 mg), K3PO4 (240 mg), and /7-BuOH (4 mL). The mixture was de-gassed, placed under an atmosphere of nitrogen and heated in a microwave reactor at 150 C for 15 min. The reaction mixture was filtered and washed with CH2Cl2. The filtrate was concentrated and the resulting residue purified by column chromatography to give 18a (141 mg, 46% yield) as light yellow crystals. 1H NMR (CDCl3) delta 9.17 (d, J = 4.5 Hz, 1 H), 9.07 (d, <n="73"/>J= 2.2 Hz, IH), 9.02 (d, J= 2.2 Hz, IH ), 8.68 (s, I H), 8.30 - 8.36 (m, 2H), 7.95 (dd, J = 7.0, 1.3 Hz, 1 H), 7.92 (d, J = 4.5 Hz, 1 H), 7.68 - 7.76 (m, 3H), 7.24 (d, J = 8.8 Hz, 2H), 3.74 - 3.82 (m, 4H), 3.40 - 3.48 (m, 4H), 1.66 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 101℃; | Synthesis of Methyl 5-nitro-4-quinolin-4-yl-lH-pyrrole-2-carboxylate (23) via Scheme 4; A mixture of methyl 4-bromo-5-nitro-l//-pyrrole-2-carboxylate (22, 124 mg, 0.5 mmol), <strong>[371764-64-6]quinoline-4-boronic acid</strong> (174 mg, 1.0 mmol), Pd (PPh3)4 (1 16 mg, 0.1 mmol), 2.0 M Na2CO3 (0.5 mL), and 1,4-dioxane (6 mL) was stirred overnight at 101 0C, then cooled to rt, diluted with water, and extracted with ethyl acetate. The organic phase was washed with water, dried (Na2SO4) and concentrated. The residue was purified by column chromatography on silica gel using CH2Cl2/MeOH (95:5) to give 23 as a yellow solid (90 mg, 60%). 1H NMR (DMSO-d6, 500 MHz) delta 14.5 (br.s, IH), 8.95 (d, J = 4.5 Hz, I H), 8.10 (d, J = 3.5 Hz, IH), 7.79 (m, IH), 7.68 (d, J= 3.5 Hz, IH), 7.56 (m, IH), 7.53 (d, J = 4.5 Hz, IH), 7.07 (s, IH), 3.89 (s, 3H); mp 204-205 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With caesium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; water; for 18h;Inert atmosphere; Reflux; | A mixture of 6-bromo-l, 2, 2-trimethyl-2, 3- dihydrothieno[3,2-d]pyrimidin-4 (IH) -one (138 mg, 0.50 mmol) , <strong>[371764-64-6]quinolin-4-ylboronic acid</strong> (173 mg, 1.00 mmol), cesium carbonate (489 mg, 1.50 mmol), 1, 2-dimethoxyethane (5 mL) and water (1 mL) was purged with argon. Then, 1,1'- bis (diphenylphosphino) ferrocenepalladium (II) dichloride dichloromethane adduct (40.8 mg, 0.050 mmol) was added, and the mixture was purged with argon again. This mixture was refluxed for 18 h. Then, the mixture was poured into saturated aqueous NaHCO3 (100 mL) and extracted with EtOAc (100 mL) , and the extract was washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. This residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc then to 90:10 EtOAc/MeOH) . The obtained yellow solid (62 mg) was triturated with EtOAc/hexane, and the precipitate was collected by filtration to afford the title compound (47.2 mg, 29%) as a pale yellow solid:1H NMR (300 MHz, DMSO-d6) delta 1.47 (6H, s) , 2.49 (3H, s) , 7.27 (IH, s), 7.63 (IH, d, J = 4.5 Hz), 7.69-7.76 (2H, m) , 7.86 (IH, t, J = 7.8 Hz), 8.13 (IH, d, J = 8.4 Hz), 8.32 (IH, d, J = 8.7 Hz), 8.95 (IH, d, J = 4.8 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | With pyridine; copper diacetate; In dichloromethane; at 20℃; for 216h;Molecular sieve; | PREPARATION 34 tert-Butyl (5-methyl-3-phenyl-1-quinolin-4-yl-1 H-pyrazol-4-yl)acetateThe title compound of Preparation 18 (100 mg, 0.37 mmol) was reacted with quinolin- 4-ylboronic acid (127 mg, 0.73 mmol), copper (II) acetate (100 mg, 0.55 mmol) and pyridine (60 muIota, 0.74 mmol) in 5 ml dichlorometane with 4A molecular sieves. The mixture was stirred at room temperature with a stream of air bubbled through for 9 days. The mixture was filtered through celite and the combined organics were evaporated. The resulting residue was purified by reverse-phase chromatography using the SP1 Purification System to give 39 mg (0.097 mmol, 27%) of the title compound as an orange oil. Purity 100%.1H NMR (400 MHz, CHLOROFORM-d) delta ppm 1.47 (s, 9 H), 2.17 (s, 3 H), 3.60 (s, 2 H), 7.35 - 7.40 (m, 1 H), 7.44 (t, J=7.42 Hz, 2 H), 7.56 (d, J=8.21 Hz, 1 H), 7.66 - 7.78 (m, 5 H), 8.10 (d, J=7.82 Hz, 1 H).HPLC/MS (9 min) retention time 6.93 min.LRMS: m/z 400 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | General procedure: To a glass vial were added benzoic acid (500 mg, 4.094 mmol,1.0 equiv), K3PO4 (3.04 g, 14.33 mmol, 3.5 equiv) in 1,4-dioxane (12 mL). This reaction mixture was stirred for 5 min at rt under nitrogen atmosphere. After this 2-chloro-1,3-dimethyl imidazolidinium chloride (830 mg, 4.91 mmol,1.2 equiv) was added to the reaction mixture and stirred for 2 h at rt. To this reaction mixture was added phenyl boronic acid (750 mg, 6.14 mmol, 1.5 equiv) and tetrakis(triphenylphosphine)palladium (95 mg, 0.08 mmol, 0.02 equiv).Reaction was purged again with nitrogen for 5 min. Vial was sealed and heated at 90 C for 16 h. The reaction mixture was cooled to rt, filtered through Celite bed, and washed with ethyl acetate. Filtrate was concentrated under vacuum. The resulting material was purified by flash chromatography on Combiflash using 12g SNAP cartridge and eluted with 0-5% ethyl acetate in hexane to give benzophenone (522 mg, 70% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 120℃; for 0.5h;Inert atmosphere; Microwave irradiation; | General procedure: In a muwave vial, 4-(4-(3-iodopyrazolo[1,5-a]pyrimidin-6-yl)phenyl)morpholine, 12, (17 mg, 0.041 mmol, 1.0 eq), phenyl boronic ester (6.0 mg, 0.046 mmol, 1.1eq), and Pd(dppf)Cl2?DCM (2 mg, 0.002 mmol, 0.05 eq) were added. The solid mixture was evacuated under vacuo and purged with Argon (3x). To the mixture was added 1,4-dioxane (2 mL), followed by a solution of K3PO4 (18 mg, 0.084 mmol, 2.0 eq) in H2O (1.0 mL). The reaction was heated to 120 C for 30 min under microwave irradiation. The reaction was added to EtOAc: H2O (1:1, 40 mL). The organic layer was separated, washed with H2O (15 mL), Brine (15 mL), dried (MgSO4), filtered and concentrated. The material was purified by reverse-phase HPLC (25-85% acetonitrile: H2O w/ 0.1% TFA) to afford 4-(4-(3-phenylpyrazolo[1,5-a]pyrimidin-6-yl)phenyl)morpholine, 13e, (8.3 mg, 43% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 120℃; for 0.5h;Inert atmosphere; Microwave irradiation; | General procedure: In a muwave vial, 4-(4-(3-iodopyrazolo[1,5-a]pyrimidin-6-yl)phenyl)morpholine, 12, (17 mg, 0.041 mmol, 1.0 eq), phenyl boronic ester (6.0 mg, 0.046 mmol, 1.1eq), and Pd(dppf)Cl2?DCM (2 mg, 0.002 mmol, 0.05 eq) were added. The solid mixture was evacuated under vacuo and purged with Argon (3x). To the mixture was added 1,4-dioxane (2 mL), followed by a solution of K3PO4 (18 mg, 0.084 mmol, 2.0 eq) in H2O (1.0 mL). The reaction was heated to 120 C for 30 min under microwave irradiation. The reaction was added to EtOAc: H2O (1:1, 40 mL). The organic layer was separated, washed with H2O (15 mL), Brine (15 mL), dried (MgSO4), filtered and concentrated. The material was purified by reverse-phase HPLC (25-85% acetonitrile: H2O w/ 0.1% TFA) to afford 4-(4-(3-phenylpyrazolo[1,5-a]pyrimidin-6-yl)phenyl)morpholine, 13e, (8.3 mg, 43% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | Step 2: A mixture of 3-phenyl-quinoxalin-2-ol (50 mg; 0.22 mmol) and bromotripyrrolidinophosphonium hexafluorophosphate (126 mg; 0.27 mmol) in dioxane (2 mL) was placed in a sealed tube. Nitrogen gas was bubbled through the reaction mixture for 2 min, before triethylamine (0.09 mL; 0.67 mmol) was added and the reaction mixture was stirred at room temperature for 4 h. Quinoline-4- boronic acid (78 mg; 0.45 mmol), sodium carbonate (119 mg; 1.12 mmol) and bis(triphenylphosphene)palladium(ll)chloride (7.9 mg; 0.01 mmol) were added, followed by water (1 mL) and the tube was sealed. The reaction mixture was heated at 100 C overnight. The reaction mixture was cooled to room temperature, diluted with water (2 mL), brine (2 mL) and ethyl acetate (100 mL). The aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by chromatography using heptane /ethyl aetate (0% to 100%) as eiuent to give title compound 2-phenyl-3-quinolin-4-yl-quinoxaline (30 mg; 40%) as a yellow solid;LCMS (ESI) 334 (M+H); HPLC 98.9%, RT: 4.29 min; 1H NMR (400 MHz, DMSO-d6) delta ppm: 8.92 (d, J=4.3 Hz, 1 H), 8.26 - 8.31 (m, 1 H), 8.18 - 8.23 (m, 1 H), 8.07 (d, J=8.5 Hz, 1 H), 7.93 - 8.04 (m, 2H), 7.66 - 7.77 (m, 2H), 7.56 (d, J=4.3 Hz, 1H), 7.49 (ddd, J=8.3, 7.0, 1.1 Hz, 1 H), 7.39 - 7.44 (m, 2H), 7.16 - 7.28 (m, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; at 110℃; for 0.75h;Inert atmosphere; | To (3i?,55)-tert-butyl 4-(4-(3-bromopyrazolo[l,5-a]pyrimidin-6-yl)phenyl)-3,5- dimethylpiperazine-1 -carboxylate (0.159 g, 0.327 mmol) and <strong>[371764-64-6]quinolin-4-ylboronic acid</strong> (0.113 g, 0.654 mmol) in dioxane (3.5 mL) was added 2 M Na2C03 (0.8 mL). Bubbled N2 through solution for 5 min then added Pd(PPh3)4 (0.038 g, 0.033 mmol). Capped and heated in 110 degree bath. After 40 min reaction was complete. Partitioned between EA and water. Washed org layer 2x with brine, dried (Na2S04), filtered and concentrated in vacuo. Obtained (3i?,55)-tert-butyl 3,5-dimethyl-4-(4-(3-(quinolin-4-yl)pyrazolo[l,5-a]pyrimidin- 6-yl)phenyl)piperazine-l -carboxylate (0.135 g, 0.253 mmol, 77 % yield) as a beige solid after trituation with methanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | In an analogous manner to Scheme 5, 4-(6-(3-chloro-4-(2-(piperidin-l- yl)ethoxy)phenyl)pyrazolo[l,5-a]pyrimidin-3-yl)quinoline, TFA was obtained from 3- bromo-6-(3-chloro-4-(2-(piperidin- 1 -yl)ethoxy)phenyl)pyrazolo[ 1 ,5-a]pyrimidine and <strong>[371764-64-6]quinoline-4-boronic acid</strong> in 54% yield after reverse phase purification. 1H NMR (400 MHz, DMSO-de) delta 9.73 (d, J= 2.3 Hz, 1H), 9.39 (s, 1H), 9.13 (d, J= 2.3 Hz, 1H), 9.04 (d, J= 4.7 Hz, 1H), 8.81 (s, 1H), 8.27 (d, J= 8.2 Hz, 1H), 8.18 - 8.09 (m, 2H), 7.97 - 7.84 (m, 3H), 7.69 (t, J= 7.7 Hz, 1H), 7.41 (d, J= 8.7 Hz, 1H), 4.53 (t, J= 4.9 Hz, 2H), 3.60 (d, J= 5.1 Hz, 4H), 3.12 (d, J= 11.4 Hz, 2H), 1.87 (d, J= 13.3 Hz, 2H), 1.71 (s, 3H), 1.42 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h; | Step 1. A mixture of 4,6-dichloro-N-(4-(trifluoromethyl)phenyl)pyrimidin-2-amine (60 mg, 0.2 mmol), <strong>[371764-64-6]quinolin-4-ylboronic acid</strong> (52 mg, 0.3 mmol), Pd(PPh3)4 andK2C03 in dioxane (1 mL) and water (0.2 mL) was heated to 100C for 30 minutes. The resulting crude mixture was purified by column chromatography to yield 4-chloro-6- (quinolin-4-yl)-N-(4-(trifluoromethyl)phenyl)pyrimidin-2-amine (34 mg, 42%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37 mg | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; N,N-dimethyl-formamide; at 100℃; for 18h;Inert atmosphere; | Example 44. Preparation of Compound No. 94 [0202] N-(4-(2-Bromothiazol-4-yl)-3-chlorophenyl)-l, 1, 1-trifluoromethane sulfonamide (100 mg, 0.2380 mmol) and 4-quinolyl boronic acid (61.7 mg, 0.3571 mol), sodium carbonate (63 mg, 0.595 mmol), dimethyl formamide (4 mL), water (1.0 mL) were charged in a 25 mL glass bottle and aerated with nitrogen gas for 5 min. After adding Pd(PPh3)4 (27.4 mg, 0.0238 mmol) re- purged the mixture for 2 min and was heated to 100 C for 18 h. The reaction was monitored by LCMS. The reaction mixture was allowed to cool to RT, water (10 mL) was added and the mixture extracted with EtOAc (3x25 mL). The combined organic layer was washed with water (4x30 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a crude product, which was purified by reverse phase HPLC to afford N-[3-chloro-4-[2- (4-quinolyl)thiazol-4-yl]phenyl]-l,l,l-trifluoro-methanesulfonamide (37 mg) as a white solid. 1H NMR (400 MHz, Methanol-d4) delta (ppm): 7.94 (s, 1H), 7.89 (d, J = 8.5 Hz, 1H), 7.57 - 7.48 (m, 1H), 7.46 - 7.38 (m, 4H), 7.31 (dd, J = 8.5, 2.3 Hz, 2H), 6.16 (s, 1H), 5.64 (s, 1H). LCMS (M+l): 445.3. |
37 mg | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; N,N-dimethyl-formamide; at 100℃; for 18h; | N-(4-(2-Bromothiazol-4-yl)-3-chlorophenyl)-1,1,1-trifluoromethane sulfonamide (100 mg, 0.2380 mmol) and 4-quinolyl boronic acid (61.7 mg, 0.3571 mol), sodium carbonate (63 mg, 0.595 mmol), dimethyl formamide (4 mL), water (1.0 mL) were charged in a 25 mL glass bottle and aerated with nitrogen gas for 5 min. After adding Pd(PPh3)4 (27.4 mg, 0.0238 mmol) re-purged the mixture for 2 min and was heated to 100 C. for 18 h. The reaction was monitored by LCMS. The reaction mixture was allowed to cool to RT, water (10 mL) was added and the mixture extracted with EtOAc (3*25 mL). The combined organic layer was washed with water (4*30 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a crude product, which was purified by reverse phase HPLC to afford N-[3-chloro-4-[2-(4-quinolyl)thiazol-4-yl]phenyl]-1,1,1-trifluoro-methanesulfonamide (37 mg) as a white solid. 1H NMR (400 MHz, Methanol-d4) delta (ppm): 7.94 (s, 1H), 7.89 (d, J=8.5 Hz, 1H), 7.57-7.48 (m, 1H), 7.46-7.38 (m, 4H), 7.31 (dd, J=8.5, 2.3 Hz, 2H), 6.16 (s, 1H), 5.64 (s, 1H). LCMS (M+1): 445.3. |
37 mg | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; N,N-dimethyl-formamide; at 100℃; for 18h;Inert atmosphere; | N-(4-(2-Bromothiazol-4-yl)-3-chlorophenyl)-1,1,1-trifluoromethane sulfonamide (100 mg, 0.2380 mmol) and 4-quinolyl boronic acid (61.7 mg, 0.3571 mol), sodium carbonate (63 mg, 0.595 mmol), dimethyl formamide (4 mL), water (1.0 mL) were charged in a 25 mL glass bottle and aerated with nitrogen gas for 5 min. After adding Pd(PPh3)4 (27.4 mg, 0.0238 mmol) re-purged the mixture for 2 min and was heated to 100 C. for 18 h. The reaction was monitored by LCMS. The reaction mixture was allowed to cool to RT, water (10 mL) was added and the mixture extracted with EtOAc (3*25 mL). The combined organic layer was washed with water (4*30 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a crude product, which was purified by reverse phase HPLC to afford N-[3-chloro-4-[2-(4-quinolyl)thiazol-4-yl]phenyl]-1,1,1-trifluoro-methanesulfonamide (37 mg) as a white solid. 1H NMR (400 MHz, Methanol-d4) delta (ppm): 7.94 (s, 1H), 7.89 (d, J=8.5 Hz, 1H), 7.57-7.48 (m, 1H), 7.46-7.38 (m, 4H), 7.31 (dd, J=8.5, 2.3 Hz, 2H), 6.16 (s, 1H), 5.64 (s, 1H). LCMS (M+1): 445.3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82 mg | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 100℃; for 6h; | Example 77 6-(quinolin-4-yl)-N-[4-(trifluoromethyl)phenyl]pyrazin-2-amine A mixture of 6-chloro-N-(4-(trifluoromethyl)phenyl)pyrazin-2-amine (55 mg, 0.20 mmol), <strong>[371764-64-6]quinolin-4-ylboronic acid</strong> (52 mmol, 0.30 mmol), K2CO3 (55 mg, 0.40 mmol) and tetrakis(triphenylphosphine)palladium(0) in dioxane (1 mL) and water (0.2 mL) was heated for 6 hours at 100C. The resulting crude product was directly loaded onto a short pad of silica gel and purified by column chromatography to provide the title compound as an off white solid (82 mg). ]H NMR (500 MHz, Acetone-i delta 9.41 (1 H, br. s.) 9.07 (1 H, d, 7=4.41 Hz) 8.47 (1 H, d, 7=0.63 Hz) 8.45 (1 H, d, 7=0.63 Hz) 8.40 (1 H, dd, 7=8.51, 0.95 Hz) 8.21 (1 H, d, 7=7.88 Hz) 8.05 (2 H, d, 7=8.51 Hz) 7.86 (1 H, ddd, 7=8.43, 6.86, 1.42 Hz) 7.77 (1 H, d, 7=4.41 Hz) 7.66 - 7.71 (1 H, m) 7.58 - 7.62 (2 H, m); MS m/z 367.1 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 90℃;Sealed tube; | A microwave vial was charged with 6-bromo-3-iodo-N,N-bis(4-methoxybenzyl)- 2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)benzenesulfonamide (1.00 g, 1.27 mmol), quinolin-4- ylboronic acid (0.481 g, 2.78 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.103 g, 0.127 mmol) and sodium carbonate (0.402 g, 3.80 mmol). The vial was sealed, degassed, and filled with dioxane (6.33 mL) and water (2.1 1 mL). The resulting mixture was heated overnight at 90C. The reaction mixture was filtered over celite to removed palladium. The filtrate was diluted with EtOAc and washed with water. The organic layer was dried over anhydrous MgS04, filtered, concentrated and purified by silica gel column chromatography using 15-60% EtOAc/Hexanes as mobile phase to afford the title compound. LC-MS (IE, m/z): 793.60[M+2]+. | |
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 90℃;Sealed tube; | Step B: 6-bromo-N,N-bis(4-methoxybenzyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)-3-(quinolin-4-yl)benzenesulfonamide (0750) A microwave vial was charged with 6-bromo-3-iodo-N,N-bis(4-methoxybenzyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)benzenesulfonamide (1.00 g, 1.27 mmol), <strong>[371764-64-6]quinolin-4-ylboronic acid</strong> (0.481 g, 2.78 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.103 g, 0.127 mmol) and sodium carbonate (0.402 g, 3.80 mmol). The vial was sealed, degassed, and filled with dioxane (6.33 mL) and water (2.11 mL). The resulting mixture was heated overnight at 90 C. The reaction mixture was filtered over celite to removed palladium. The filtrate was diluted with EtOAc and washed with water. The organic layer was dried over anhydrous MgSO4, filtered, concentrated and purified by silica gel column chromatography using 15-60% EtOAc/Hexanes as mobile phase to afford the title compound. LC-MS (IE, m/z): 793.60[M+2]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 2h;Inert atmosphere; | ethyl 2-(4-(((trifluoromethyl)sulfonyl)oxy)cyclohex-3-en-1-yl)acetate 1b (316 mg, 1 mmol), <strong>[371764-64-6]quinolin-4-ylboronic acid</strong> ( 173mg, 1mmol),[1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride dichloromethane complex (81.7 mg, 0.1 mmol), potassium carbonate (276 mg, 2.0 mmol), water (5 ml) and 1,4-Dioxane (10 ml) was heated to 100 C under nitrogen and stirring was continued for 2 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified by silica gel column chromatography(petroleum ether/ethyl acetate = 50/1 to 10/1), To give the desired product ethyl 2-(4-(quinolin-4-yl)cyclohex-3-en-1-yl)acetate 1c (200mg, yellow oil). Yield: 63%. |
58% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; potassium bromide; In 1,4-dioxane; water; at 100℃; for 14h;Inert atmosphere; | Ethyl 2-(4-(((trifluoromethyl)sulfonyl)oxy)cyclohex-3-en-1 -yl)acetate (10 g, 31 .6 mmol), <strong>[371764-64-6]quinolin-4-ylboronic acid</strong> (8.2 g, 47.4 mmol), Pd(PPh3)4 (3.65 g, 3.16 mmol) and KBr (4.14 g, 34.8 mmol) were dissolved in dioxane (100 ml_). After adding 2 M aqueous sodium carbonate solution (40 ml_), the mixture was stirred under nitrogen atmosphere at 100C for 14 hours. After the reaction mixture was cooled to room temperature, this was partitioned between water and EtOAc and the layers were separated. The organics were washed sequentially with water and brine, and dried over Na2S04. Filtration and concentration in vacuum gave a crude product, which was purified by flash chromatography to afford the title compound (5.4 g, 58% yield). (ESI) m/z calcd for C19H21 NO2: 295.16. Found: 296.58 (M+1 )+. |
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; potassium bromide; In 1,4-dioxane; water; at 80 - 90℃; for 16h; | General procedure: To ethyl 2-(4-(((trifluoromethyl)sulfonyl)oxy)cyclohex-3-en-l-yl)acetatei: (1.0 eq.), boronic acid (1.2 equiv), Na2C03 (2.5 eq.), KBr (1.1 eq.) in 1 ,4-dioxane/water (10:1 by volume, 0.25M) was added Pd(PPh3)4 (5 mol.%). The resulting reaction mixture was heated to 80-90 C for 16 h, upon which the crude reaction mixture was concentrated. The resulting solids were diluted with EtOAc and water and the layers were separated. The aqueous layer was extracted with EtOAc thrice. The combined organic extracts were dried over anhydrous MgS04, filtered, and concentrated under reduced pressure. The crude reaction mixture was purified employing silica gel chromatography to afford the desired product. * Ethyl 2-(4-(((trifluoromethyl)sulfonyl)oxy)cyclohex-3-en-l-yl)acetate is a known compound that can be prepared from commercially available l,4-dioxaspiro[4.5]decan-8- one using the procedures outlined in 1) Stocks, P.A. et al, Angew. Chem. Int. Ed., 46:6278-6283 (2007); 2) Barlind, J.G. et al, J. Med. Chem., 55: 10610-10629 (2012). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.8 g | With sodium carbonate; In ethanol; water; toluene; for 2h;Inert atmosphere; Reflux; | Under a nitrogen atmosphere and at reflux temperature there was added 8-bromo-5,9-dioxa-oxo -13b- HETEROPOLYACID naphtho [3,2,1-de] anthracene (1.5g), 4- quinolineboronic acid (0.8g), Pd-132 (0.03g), sodium carbonate (1.0g), toluene (40ml), ethanol(10ml) and water (10ml) was stirred for 2 hours the flask was heated. The reactionmixture was cooled until room temperature, water and toluene were separated. Then, theuse of activated alumina column chromatography (eluent: toluene / ethyl acetate mixedsolvent) to be purified. In this case, refer to "Organic Chemistry Getting Started (1) -substance approach and separation and purification method -" Chemical Publishing Co.,colleagues, the method described on page 94, the developing solution is slowly increasedin the ratio of ethyl acetate to make the target dissolution. The solvent fractioncontaining the desired compound were evaporated under reduced pressure, toreprecipitate, which is obtained from the formula (1-3824) represented by the compound(0.8g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67.1% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; at 110℃; for 8h;Inert atmosphere; | The first step: nitrogen protection,To a condenser equipped with a condenser, mechanical stirring,Thermometer and constant pressure dropping funnelL round bottom flask was charged with 1-bromo-9-fluorenone (25.797 g, 0.1 mol, 1.0 eq)Quinoline-4-boronic acid(20.76 g, 0.12 mol, 1.2 eq), Pd (dppf) Cl2 (2.5 g, 0.003 mol, 0.03 eq), Cs2CO3 (97.5 g, 0.3 mol, 3.0 eq)Then, to the above mixture was added 1 L of dioxane,After this time the mixture in the round bottom flask was stirredThe mixture was allowed to react at 110 C for 8 hours and then cooled to room temperature.The contents of the above cooled flask were dried and 600 ml of deionized water and 600 ml of ethyl acetate were added to the residue. After stirring at 30 C for a few minutes, the mixture was allowed to stand. After the organic phase and the aqueous phase were separated, . The separated organic layer was washed three times with water (600 ml each time) and three times with saturated brine (600 ml each time with saline). The washed organic phase was dried over anhydrous sodium sulfate, filtered off and dried. The resulting product was purified by column chromatography using ethyl acetate / petroleum ether (2: 3, v / v) as mobile phase. The purified product was purified at 50 C And dried under vacuum to give 1- (4-quinolyl) -9-fluorenone (20.569 g, yield: 67.1%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | And then the dissolved intermediate 3-1 (1g, 2.46mmol) in 30mL DMF, to put the sodium hydride and stirred for 1 hour. The intermediate C (0.8g, 2.95mmol) to put the reaction mixture is dissolved in 10mL DMF and stirred for 12 hours at room temperature. After washing the resultant precipitate in methylene chloride and placed in a heating Dichlorobenzene himyeo expression to room temperature and recrystallized to give the separated compound 3 (1.14g, 65%). The resulting compound was confirmed by LC-MS and NMR. Intermediate 3-1 and Intermediate C instead of Intermediate 60-1 and the intermediate I was used, respectively, except that the compound 60 using the same method and the third method of synthesizing compounds of the above Synthesis Example 1 (51% yield) It was synthesized. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 85℃;Sealed tube; | Step A: 6-Bromo-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)-3-(quinolin-4-yl)benzenesulfonamide (1009) Quinolin-4-ylboronic acid (0.629 g, 3.64 mmol), 6-bromo-3-iodo-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide (1 g, 1.818 mmol), Na2CO3 (0.385 g, 3.64 mmol), PdCl2(dppf) (0.133 g, 0.182 mmol) was placed in a reaction vessell, and 1,4-dioxane (9.09 ml) and water (3.03 ml) were added. The reaction was sealed, degassed for 20 min and then heated at 85 C. overnight. After cooling to room temperature, the reaction mixture was diluted with EtOAc and washed with water. The organic phase was separated and concentrated. The resulting residue was purified by column chromatography (0% to 90% EtOAc/Hexane) to give 6-bromo-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)-3-(quinolin-4-yl)benzenesulfonamide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With [2,2]bipyridinyl; nickel(II) bromide dimethoxyethane; potassium phosphate; In 1,2-dimethoxyethane; at 80℃; for 30h;Inert atmosphere; Sealed tube; | Under a nitrogen atmosphere, 4-quinolinoboric acid (25.95 g, 150 mmol) was added sequentially in a sealed tube, Anhydrous potassium phosphate (42.45 g, 200 mmol), After addition of solvent ethylene glycol dimethyl ether (100 mL), the mixture was stirred, A solution of 2-chloro-1,1,1-trifluoroethane in ethylene glycol dimethyl ether (1 mol / L, 100 mL) was added successively, 2,2'-bipyridyl (0.78 g, 5 mmol) And NiBr2 (DME) (1.54 g, 5 mmol) After sealing, the reaction was stirred in an oil bath at 80 C for 30 hours, The reaction solution was cooled to room temperature, The insoluble matter in the reaction solution was filtered off with a diatomite sand core funnel, Rinse a small amount of ether and collect the filtrate. To the filtrate was added 600 mL of water, extracted with ether (400 mL x 3) The organic phase was combined and the organic phase was washed successively with water, saturated brine, Dried over anhydrous sodium sulfate, filtered, The solvent was recovered by rotary evaporation and the residue was purified by recrystallization. The product was 17.31 g in 82% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; at 100℃; for 4h;Inert atmosphere; | To a round-bottom flask was charged with Cpd. No. 2 (10 mg, 0.033 mmo <strong>[371764-64-6]quinolin-4-ylboronic acid</strong> (12 mg, 2 eq), Pd(dppf)Cl2 (3 mg). Under N2 atmosphere, dioxane (1 mL) and a solution of Na2C03 (2.0 M, 0.5 mL) was added. The reaction mixture was heated at 100 C for 4 h prior to being taken up in EtOAc and water. The organic layer was separated, evaporated to give a crude mixture which was purified via HPLC to provide the TFA salt of Cpd. No. 5 (80% yield).1H NMR (400 MHz, CDC13) 5 9.39 (d, = 5.2 Hz, 2H), 8.61 (d, 7 = 8.6 Hz, 1H), 8.12 (ddd, J = 8.5, 7.0, 1.3 Hz, 1H), 7.92 - 7.85 (m, 1H), 7.85 - 7.78 (m, 1H), 7.74 (d, = 5.2 Hz, 1H), 4.95 (d, = 14.3 Hz, 1H), 4.88 (d, = 14.3 Hz, 1H), 4.47 (d, = 15.2 Hz, 1H), 4.35 (d, = 15.2 Hz, 1H), 2.94 (s, 2H), 2.32 (s, 3H). ESI-MS: 349.10. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5% | With oxygen; copper diacetate; triethylamine; In dichloromethane; at 20℃; | To a mixture of crude IS (2 g, 13.1 mmol), phenylboronic acid (1.93 g, 15.7 mmol), TEA (2.64 g, 26.1 mmol), Py (2.07 g, 26.1 mmol) in DCM (20 mL) is added Cu(OAc)2 (3.56 g, 19.6 mmol). After reacting at room temperature overnight under oxygen, the mixture is filtered, concentrated, and purify by silica gel column chromatography (MeOH:DCM = 1 :50) to give 16 as a yellow solid (2.3 g, 77% yield), (MS: | VI · H | 230.1).Following the procedure for 16 using El (200 mg. 0.58 rnmoi), DCM (10mL), quinoline-4-horonic acid (301 111g. 174 mrnoi), Cu(OAc)2 (116 rng. 0.64 mmol), andTEA (04 mL. 0,9 mmoi), purify with prep-TLC (MeOH:DCM = 1:20) to give Ex204 as ayellow solid (15 mg, 5% yield). (MS: [M±Hj 471.1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In butan-1-ol; at 110℃; for 3h;Inert atmosphere; | 5-Bromo-2-methoxypyridin-3-amine (100 mg, 0.49 mmol, 1 equivalent), <strong>[371764-64-6]quinoline-4-boronic acid</strong> (102 mg, 0.59 mmol, 1.2 equivalents), potassium phosphate (314 mg, 1.48 mmol, 3 equivalents), 2-dicyclohexylphosphino-2,4,6-triisopropylbiphenyl (47 mg, 0.10 mmol, 0.2 equivalents) and tris(dibenzylideneacetone)dipalladium(0) (22.55 mg, 0.025 mmol, 0.05 equivalents) were dissolved in n-butanol (4 mL) and stirred at 110 C for 3 hours. The solution was then cooled and filtered through a pad of celite, which was then washed with methanol. The solution was concentrated and purified by SCX column (eluting at room temperature with 2 M ammonia in methanol) and concentrated. The residue was then dissolved in acetonitrile and sodium iodide (222 mg, 1.484 mmol, 3 equivalents) was added followed by dropwise addition of trimethylsilyl chloride (0.190 mL, 1.484 mmol, 3 equivalents) and the reaction mixture stirred for 16 hours. The solution was concentrated, taken up in methanol and purified by SCX column (eluting at room temperature with 2 M ammonia in methanol) followed by column chromatography (5% MeOH in EtOAc) to give the product as a grey solid (33 mg, 24%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; N,N-dimethyl-formamide; at 100℃; for 16h; | Compound 65 (830 mg, 2.43 mmol) was taken up in 1 ,4-dioxane/DMF (3: 1, 10 mL). Potassium carbonate (550 mg, 3.99 mmol), [ 1 , 1 '-bis(diphenylphosphino)- ferrocene]dichloropalladium(II) (190 mg, 0.26 mmol) and <strong>[371764-64-6]quinolin-4-ylboronic acid</strong> (450 mg, 2.60 mmol) were added. After sparged with nitrogen for 10 min, the mixture was heated at 100 C for 16 h, cooled, and filtered. The filtrate was concentrated. The residue was purified by flash chromatography (silica gel, 0 to 30% EtOAc in hexanes) to give compound 67 (160 mg, 15% yield) as a foamy solid, m/z = 434 (M+l). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; palladium diacetate; triphenylphosphine; In 1,2-dimethoxyethane; N,N-dimethyl-formamide; at 110℃; for 5h;Microwave irradiation; | Compound 23 (50 mg, 0.16 mmol), uinolone-4-boronic acid (45 mg, 0.26 mmol), triphenylphosphine (17 mg, 0.065 mmol), potassium phosphate (108 mg, 0.51 mmol) and palladium acetate (7.6 mg, 0.034 mmol) were weighed in a vial, and kept under vacuum. 1 ,2-dimethoxyethane (0.7 mL) and DMF (0.35 mL) (sparged with nitrogen for 5 min) were added. The vial was filled with nitrogen, and was heated in Biotage microwave synthesizer at 1 10 C for 5 h. The mixture was cooled to room temperature, filtered through a silica gel plug, and eluted with EtOAc. The filtrate was washed with water. The organic extract was dried with Na2SC>4, and concentrated. The residue was purified by flash chromatography (silica gel, eluting with 0% to 50% EtOAc in hexanes) to give partially purified product, which was purified again by flash chromatography (silica gel, eluting with 0% to 10% acetone in CH2CI2) to give a mixture of compound 24 and 25 (15 mg, 23% yield) as a glassy solid. The mixture was dissolved in MeOH (0.72 mL). Sodium methoxide (25 wt.% in methanol, 13 muL, 0.056 mmol) was added. The reaction mixture was stirred at 55 C for 1.5 h, and cooled to rt. EtOAc was added. The mixture was washed with aq. 10% KH2PO4. The organic extract was dried with Na2S0 and concentrated to give compound 25. m/z = 413 (M+l). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Compound 23 (50 mg, 0.16 mmol), uinolone-4-boronic acid (45 mg, 0.26 mmol), triphenylphosphine (17 mg, 0.065 mmol), potassium phosphate (108 mg, 0.51 mmol) and palladium acetate (7.6 mg, 0.034 mmol) were weighed in a vial, and kept under vacuum. 1 ,2-dimethoxyethane (0.7 mL) and DMF (0.35 mL) (sparged with nitrogen for 5 min) were added. The vial was filled with nitrogen, and was heated in Biotage microwave synthesizer at 1 10 C for 5 h. The mixture was cooled to room temperature, filtered through a silica gel plug, and eluted with EtOAc. The filtrate was washed with water. The organic extract was dried with Na2SC>4, and concentrated. The residue was purified by flash chromatography (silica gel, eluting with 0% to 50% EtOAc in hexanes) to give partially purified product, which was purified again by flash chromatography (silica gel, eluting with 0% to 10% acetone in CH2CI2) to give a mixture of compound 24 and 25 (15 mg, 23% yield) as a glassy solid. The mixture was dissolved in MeOH (0.72 mL). Sodium methoxide (25 wt.% in methanol, 13 muL, 0.056 mmol) was added. The reaction mixture was stirred at 55 C for 1.5 h, and cooled to rt. EtOAc was added. The mixture was washed with aq. 10% KH2PO4. The organic extract was dried with Na2S0 and concentrated to give compound 25. m/z = 413 (M+l). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate; In water; ethyl acetate; at 60℃; for 0.166667h;Inert atmosphere; | Compound 6 (1.13 g, 3.61 mmol) was dissolved in 96 mL of a mixture of H2O:EtOAc (1:1) and placed in a three-necked flask(250mL). 4-Quinolinylboronic acid (3.97 mmol) and potassium carbonate (0.29 g, 2.10 mmol) were added to the mixture. Of courseThereafter, PdNPs catalyst (0.4 mmol% Pd) was added, and the mixture was vigorously stirred at 60 C for 10 minutes under a nitrogen atmosphere. willThe reaction mixture was poured into a 0.2 mol/L sodium hydroxide solution (25 mL) and extracted with ethyl acetate (30mL). Organic laminationAnd naturally evaporate in the air to give the final bright yellow solid product 7-(2-fluoro-5-(quinolin-4-yl)phenyl)-1-methylOctahydro-1H-pyrrolo[2,3-b]pyridine, 1.18 g, yield 90%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 80℃; for 2h;Inert atmosphere; | A mixture of 4-bromoquinoline (1.0 g, 4.81 mmol), bis(pinacolato)diboron (12.0 g, 47.26 mmol), PdCl2dppf (0.7 g, 0.96 mmol), potassium acetate (1.4 g, 14.29 mmol) in 1,4-dioxane (100 mL) was stirred under Ar at 80 C. for 2 hours. The reaction was concentrated to dryness. The residue was purified by silica-gel column chromatography (petroleum ether/ethyl acetate=1:1 to dichloromethane: methanol=1:1) to give the title compound as a yellow solid (2 g, crude). LCMS (ESI) [M+I-1]+=256.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100 mg | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃; for 3h;Inert atmosphere; | A mixture of trans-N-(6-bromo-8-chloro-3-isoquinolyl)-2-cyano-cyclopropanecarboxamide (800 mg, 2.28 mmol), <strong>[371764-64-6]quinoline-4-boronic acid</strong> (100 mg, 0.58 mmol), Pd(PPh3)4 (67 mg, 0.06 mmol), and K2CO3 (239 mg, 1.73 mmol) in 1,4-dioxane (4 mL) and water (1 mL) was stirred under Ar at 90 C. for 3 hours. The reaction was concentrated to dryness. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate=4:1 to petroleum ether/acetate=2:1) to give the title compound as a yellow solid (100 mg, 25.3% yield). LCMS (ESI) [M+H]+=399.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; water; at 120℃; for 2.75h;Inert atmosphere; Microwave irradiation; | Quinoline-4-boronic acid (14.17 mmol),Compound 4 (4.34 g, 14.17 mmol),Na2CO3 (4.51 g, 42.51 mmol),DME (22.95 mL) and H2O (5.67 mL) were added to a 50 mL microwave vial.The vial was degassed with N2 for 45 minutes.Then PdCl 2 (dppf) CH 2 Cl 2 (1.25 g, 1.70 mmol) adduct was added.The reaction mixture was heated at 120 C for 2 hours by microwave irradiation.The resulting mixture was diluted with EtOAc (EtOAc)EtOAc.Purified by flash chromatography using 0-100% ethyl acetate / heptane as eluent.Obtaining a white solid (5-(quinolin-4-yl)furan-2-yl)(5,6,7,8-tetrahydroquinolin-3-yl)methanone,4.37 g, yield 87%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; water; at 120℃; for 2h;Microwave irradiation; | Add <strong>[371764-64-6](quinolin-4-yl)boronic acid</strong> (14.17 mmol), compound 4 (4.19 g, 12.98 mmol), Na2CO3 (4.51 g, 42.51 mmol), DME (22.95 mL) and H2O (5.67 mL) to a 50 mL microwave vial in. The vial was degassed with N2 for 45 minutes.Then PdCl 2 (dppf) CH 2 Cl 2 (1.25 g, 1.70 mmol) adduct was added.The reaction mixture was heated at 120 C for 2 hours by microwave irradiation.The resulting mixture was treated with acetic acidThe ester is diluted and filtered through diatomaceous earth.It was then concentrated in vacuo.Purified by flash chromatography using 0-100% ethyl acetate / heptane as eluent.The white solid (2-(quinolin-4-yl)quinolin-4-yl)(5,6,7,8-tetrahydroquinolin-3-yl)methanone, 4.26 g,yield: 79%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 6h;Inert atmosphere; Reflux; | In a 2000ml four-necked flask, add intermediate M14 (61.7 g, 0.1 mol), <strong>[371764-64-6]quinoline-4-boronic acid</strong> (38.1 g, 0.22 mol), toluene (620 ml), ethanol (200 ml), water (100 ml), potassium carbonate (60.7 g, 0.44 mol), tetrakistriphenylphosphine palladium (2.3 g), three times with nitrogen, protected with nitrogen and stirred at reflux for 6 h. Stop the reaction and add ethyl acetate and water to the reaction solution. The aqueous phase was washed once with ethyl acetate (500 mL). The combined organic phases were washed once with deionized water (500 ml). The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was taken up in vacuo, dissolved in dichloromethane and purified using silica gel column chromatography. The eluent was ethyl acetate: petroleum ether = 1:8, yielding 42.1 g of a white powder solid, yield 59.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.87 g | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In ethanol;Reflux; | Ethyl 2-(5-bromothien-2-ylthio)-2-methylpropanoate (0.85 g, 2.75 mmol), quinolin-4-yl-boronic acid (0.5 g, 2.89 mmol), Pd (dppf) Cl2 (0.04 g), potassium carbonate (0.85 g, 6.16 mmol) and 1,2 dioxane and ethanol (10 ml, 1:1) were charged to the reactor and heated to reflux until the reaction was completed. Insoluble matter was removed by filtration, and the filtrate was evaporated to dryness under reduced pressure.Separation and purification (ethyl acetate / n-hexane system) to obtain the target 7c:Ethyl 2-(5-(quinolin-4-yl)thiophene-2-ylthio)-2methylpropanoate 0.87 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.87 g | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In ethanol;Reflux; | Ethyl 2-(5-bromothiophen-2-ylthio)cyclobutyl-1-carboxylate (0.88 g, 2.75 mmol), quinolin-4-yl-boronic acid (0.5 g, 2.89 mmol), Pd (dppf) Cl2 (0.04 g), potassium carbonate (0.88 g) and 1,2 dioxane and ethanol (10 ml, 1:1) were added to the reactor and heated to reflux until the reaction was completed. Insoluble matter was removed by filtration, and the filtrate was evaporated to dryness under reduced pressure.(Ethyl acetate/n-hexane system) gave the title compound 19a: ethyl (2-(5-(quinolin-4-yl)thiophen-2-ylthio)cyclobutyl-1-carboxylate, 0.87 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.1 g | 4-bromoquinoline (5.0 g, 24.03 mmol) and THF (100 ml) were added to the reactor, protected with nitrogen, and cooled to -78 C. n-butyl lithium (18 ml, 28.8 mmol) was slowly added dropwise. The reaction was kept for 2 hours, and then triisopropyl borate (7.28 g, 36.02 mmol) was added dropwise. After the completion of the dropwise addition, the mixture was slowly stirred to room temperature and stirred until the reaction was completed. Add 6M diluted hydrochloric acidAfter quenching (30 ml), EtOAc (3 mL)Column chromatography (ethyl acetate / n-hexane system) was purified to afford compound 7b:Quinoline-4-yl-boronic acid 3.1 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; potassium bromide; In 1,4-dioxane; water; at 100℃; for 14h;Inert atmosphere; | A suspension of ethyl 6-(((trifluoromethyl)sulfonyl)oxy)spiro[2.5]oct-5-ene-1 - carboxylate (2.26 g, 6.89 mmol), <strong>[371764-64-6]quinolin-4-ylboronic acid</strong> (1 .79 g, 10.34 mmol), (0180) Pd(PPh3)4 (796 mg, 0.689 mmol), Na2C03 (1 .83 g, 11 .23 mmol), KBr (902 mg, 7.58 mmol) in dioxane (20 mL) and water (2 mL) was stirred at 100C for 14 hours under nitrogen atmosphere. After the reaction mixture was cooled to room temperature, this was partitioned between water and EtOAc and the layers were separated. The organics were washed sequentially with water and brine, and dried over Na2S04. Filtration and concentration in vacuum gave a crude product, which was purified by flash (0181) chromatography to afford the title compound (1 .01 g, 48% yield). (ESI) m/z calcd for C20H21 NO2: 307.16. Found: 308.26 (M+1 )+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; sodium bromide; In 1,4-dioxane; water; at 100℃; for 14h;Inert atmosphere; | A suspension of 2-(dibenzylamino)spiro[3.5]non-6-en-7-yl (0207) trifluoromethanesulfonate (728 mg, 1 .56 mmol), <strong>[371764-64-6]quinolin-4-ylboronic acid</strong> (386 mg, 2.35 mmol), Pd(PPh3)4 (180 mg, 0.156 mmol), NaBr (177 mg, 1 .72 mmol) in dioxane (10 mL) and water (2 mL) was stirred under nitrogen atmosphere at 100C for 14 hours. After the reaction mixture was cooled to room temperature, this was partitioned between water and EtOAc and the layers were separated. The organics were washed sequentially with water and brine, and dried over Na2S04. Filtration and concentration in vacuum gave a crude product, which was purified by flash chromatography to afford the title compound (580 mg, 83% yield). (ESI) m/z calcd for C32H32N2: 444.26. Found: 445.33 (M+1)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; sodium bromide; In 1,4-dioxane; water; at 100℃; for 14h;Inert atmosphere; | A suspension of ethyl 2-(7-(((trifluoromethyl)sulfonyl)oxy)spiro[3.5]non-6-en-2- yl)acetate (220 mg, 0.62 mmol), <strong>[371764-64-6]quinolin-4-ylboronic acid</strong> (115 mg, 0.70 mmol), (0237) Pd(PPh3)4 (54 mg, 0.047 mmol), NaBr (69 mg, 0.67 mmol) and Na2C03 (148 mg, 1 .40 mmol) in dioxane (4.0 mL) and water (1 .0 mL) was stirred under nitrogen atmosphere at 100C for 14 hours. After the reaction mixture was cooled to room temperature, this was partitioned between water and EtOAc and the layers were separated. The organics were washed sequentially with water and brine, and dried over Na2S04. Filtration and concentration in vacuum gave a crude product, which was purified by flash chromatography to afford the title compound (71 mg, 34% yield). LCMS (ESI) m/z calcd for C22H25NO2: 335.19. Found: 336.35 (M+1)+. |
Tags: 371764-64-6 synthesis path| 371764-64-6 SDS| 371764-64-6 COA| 371764-64-6 purity| 371764-64-6 application| 371764-64-6 NMR| 371764-64-6 COA| 371764-64-6 structure
A281536[ 1035458-54-8 ]
4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)quinoline
Reason: Different form
[ 1035458-54-8 ]
4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)quinoline
Similarity: 0.78
[ 1035458-54-8 ]
4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)quinoline
Similarity: 0.78
[ 406463-06-7 ]
6-Quinolineboronic acid pinacol ester
Similarity: 0.70
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