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[ CAS No. 889865-34-3 ] {[proInfo.proName]}

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Chemical Structure| 889865-34-3
Chemical Structure| 889865-34-3
Structure of 889865-34-3 * Storage: {[proInfo.prStorage]}
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Product Details of [ 889865-34-3 ]

CAS No. :889865-34-3 MDL No. :MFCD22418284
Formula : C22H34BNO5 Boiling Point : -
Linear Structure Formula :- InChI Key :XPNSYBYHVPMAET-UHFFFAOYSA-N
M.W : 403.32 Pubchem ID :59320843
Synonyms :

Calculated chemistry of [ 889865-34-3 ]

Physicochemical Properties

Num. heavy atoms : 29
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.68
Num. rotatable bonds : 6
Num. H-bond acceptors : 5.0
Num. H-bond donors : 0.0
Molar Refractivity : 119.08
TPSA : 57.23 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -5.69 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.0
Log Po/w (XLOGP3) : 4.32
Log Po/w (WLOGP) : 3.38
Log Po/w (MLOGP) : 2.19
Log Po/w (SILICOS-IT) : 2.39
Consensus Log Po/w : 2.46

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -4.82
Solubility : 0.00611 mg/ml ; 0.0000152 mol/l
Class : Moderately soluble
Log S (Ali) : -5.24
Solubility : 0.00234 mg/ml ; 0.00000581 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -5.05
Solubility : 0.0036 mg/ml ; 0.00000893 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 3.74

Safety of [ 889865-34-3 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 889865-34-3 ]

* 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.

  • Downstream synthetic route of [ 889865-34-3 ]

[ 889865-34-3 ] Synthesis Path-Downstream   1~62

  • 1
  • [ 73183-34-3 ]
  • [ 346617-98-9 ]
  • [ 889865-34-3 ]
YieldReaction ConditionsOperation in experiment
61% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In dimethyl sulfoxide; at 85 - 100℃;Inert atmosphere; General procedure: A mixture of aryliodide or arylbromide (1 equiv.), bis(pinacolato)diboron (1.2 to 1.5 equiv.), OAc (3 equiv.) and DMF or DMSO was purged with Ar for 10 min. [1,1'- PdCl2dppf*CH2Cl2 (3-5 mol%) was added, the vial sealed and heated at 85-100 C for 2-3 h. The product was partitioned between EtOAc and satd aq NaHC03 solution, washed with brine, dried over Na2S04 or MgS0 , filtered, and concentrated to dryness. The crude product was purified by flash chromatography to give the title compound.
  • 2
  • [ 81971-39-3 ]
  • [ 889865-34-3 ]
  • [ 889865-35-4 ]
  • 3
  • bis(diphenylphosphino)ferrocene palladium(II) dichloride·dichloromethane [ No CAS ]
  • [ 73183-34-3 ]
  • [ 889865-34-3 ]
YieldReaction ConditionsOperation in experiment
57% With potassium acetate; In water; dimethyl sulfoxide; 2) Production of 4-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenoxy-1-t-butoxycarbonylpiperidine: Potassium acetate (2.92 g, 29.8 mmol) and bis(diphenylphosphino)ferrocene palladium(II) dichloride·dichloromethane (486 mg, 0.60 mmol) were added to a dimethylsulfoxide (35 mL) solution of the compound (4.0 g, 9.92 mmol) obtained in the above reaction and bis(pinacolato)diboron (3.27 g, 12.9 mmol), and stirred in a nitrogen atmosphere at 75C for 2 hours. The reaction mixture was cooled to room temperature, water was added to it, and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified through silica gel column chromatography (C-300, hexane/ethyl acetate = 8/1) to obtain the entitled compound (2.14 g, 57 %) as a apale yellow solid.
  • 4
  • [ 889865-34-3 ]
  • [ 1332527-13-5 ]
  • C31H35N3O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene;Inert atmosphere; Reflux; Example 37 3-Ethyl-1-phenyl-6-(4-(piperidin-4-yloxy)phenyl)-1H-indazole hydrochloride Into a 100-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 6-bromo-3-ethyl-1-phenyl-1H-indazole (225 mg, 0.75 mmol, 1.50 equiv) in toluene/ethanol at 5:1 (30 mL), <strong>[889865-34-3]tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)piperidine-1-carboxylate</strong> (200 mg, 0.50 mmol, 1.00 equiv), potassium carbonate (117 mg, 0.85 mmol, 1.70 equiv), Pd(PPh3)4 (11.5 mg, 0.01 mmol, 0.02 equiv). The resulting solution was heated to reflux overnight in an oil bath. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:20). The residue was dissolved in hydrogen chloride/EtOAc (30 mL). After stirring for 30 min, the resulting mixture was concentrated under vacuum. The residue was purified by re-crystallization from diethyl ether to yield 3-ethyl-1-phenyl-6-(4-(piperidin-4-yloxy)phenyl)-1H-indazole hydrochloride as a white solid. MS (m/z): 398 [M-HCl+H]+
  • 5
  • [ 889865-34-3 ]
  • [ 1533423-93-6 ]
  • 4-[4'-(5-amino-1H-[1,2,4]triazol-3-ylamino)-2',6'-dichlorobiphenyl-4-yloxy]piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
14% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 140℃;Inert atmosphere; Sealed tube; In a 1 5 m L sealed tube, N3-(4-bromo-3,5-dichlorophenyl)-lH-l ,2,4-triazoie-3,5-diamineIntermediate 2 (200 mg, 619 iimol, Eq : 1 .00), tetrakis(triphenylphosphine)-palladium (0) (71.6 mg, 61 .9 iimol, Eq : 0. 1 ) and tert-butyl 4-(4-(4,4,5,5-tetramethyi-l ,3,2-dioxaboroian-2- yl )pheno.xy)piperidine- 1 -carboxylate (250 mg, 61 9 iimol, Eq: 1 .00), were combined with a solution of 1 .4-dioxane TEO = 4/1 (6.67 ml ) to give a light yellow suspension. Potassium carbonate (342 mg, 2.48 mmol, Eq : 4 ) was added to the suspension. The reaction mixture was degassed with argon for 1 5 min, and then heated to 140C for overnight. The reaction mixture was cooled and diluted with CH2CI2( 50 ml.), washed with H20 ( 25 m l .) and brine (25 ni L). The organic layer was dried over anhydrous gSO.4, filtered and volatiles were removed under reduced pressure to yield an oil from which the compound was isolated by columnchromatography (CH2Ci2/MeOH = 95/5 ) to give an off-white solid (45 mg, 14%). MH+ 519.0
  • 6
  • [ 109384-19-2 ]
  • [ 269409-70-3 ]
  • [ 889865-34-3 ]
YieldReaction ConditionsOperation in experiment
69% With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; toluene; at 0 - 20℃; for 20h;Inert atmosphere; Enzymatic reaction; Triphenylphosphine (9.53 g, 36.4 mmol), and DEAD (40% w/w DEAD in toluene, 16.1 mL, 40.9 mmol) in THF (80 mL) was cooled at 0 C and stirred under nitrogen atmosphere. A mixture of 4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenol (5.0 g, 22.7 mmol) and 4-hy droxypiperi dine- 1-carboxy lie acid tert-butyl ester (5.72 g, 28.4 mmol) in THF (10 mL) was added dropwise to the reaction. The cooling bath was removed and furthered stirred at rt for 20 h. The reaction was evaporated under vacuum, stirred with ether, and the white solid filtered off. The filtrate was evaporated under vacuum and purified by ISCO silica gel chromatography ( 0-20% EtOAc / hexanes) to obtain 4-[4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)- phenoxy]-piperidine-l-carboxylic acid tert-butyl ester (6.3 g, 69%). LCMS m/z = 404 (M + 1).
38% With triphenylphosphine; 1,1'-azodicarbonyl-dipiperidine; In tetrahydrofuran; at 0 - 20℃; In a 1 00 ni L round-bottomed flask, tri phenyl hosph i n e (1.25 g, 4.77 mmol, Eq: 1.05), ivY-butyl 4-hydro.xypiperidine- 1 -carboxylate (915 mg, 4.54 mmol, Eq: 1 .00 ) and 4-( 4.4,5, 5.-tetramethyl- l ,3,2-dioxaborolan-2-yl)phenol (1 g. 4.54 mmol. Eq : 1 .00 ) were combined with THF (25.0 ml ) to give a colorless suspension. Cooled the reaction to 0C, 1 . 1 '-(azodicarbonyl )dipipcridine ( 1 .2 g, 4.77 mmol, Eq: 1.05 ) in THF (5 m l .) was added. The reaction mixture was slowly raised to room temperature and stirred overnight, concentrate the solution. The compound was purified by column chromatography (Hexanes/EtOAc = 70/30) to give 0.7 g (38%) oil. M Hi 403.9
3 g In a 500 ml round bottom flask, a mixture of fe/f-butyl 4-hydroxypiperidine-1 -carboxylate (5 g, 24.88 mmol) (CAS 109384-19-2), 4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)phenol (CAS 269409-70-3) (6 g, 27.36 mmol) and PPh3 (9.78 g, 37.31 mmol) in dry THF (200 ml) was stirred at 0 C for 5 min. Then, DIAD (10 g, 49.75 mmol) was added dropwise at 0 C and stirred for 3 h. The RM was then concentrated. Purification of the residue by flash chromatography on silica gel eluting with 20% EtOAc in petroleum ether afforded 3 g of the title compound as a white solid. LC-MS (method J): Rt = 1 .73 min, [M+NH4]+ = 404.
  • 7
  • [ 889865-34-3 ]
  • N3-[2,6-dichloro-4'-(piperidin-4-yloxy)-biphenyl-4-yl]-1H-[1,2,4]triazole-3,5-diamine HCl salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 80℃; for 4h;Inert atmosphere; General procedure: Step 2 tert-Butyl (2S)-2-[[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]methyl]pyrrolidine-1-carboxylate To a solution of the compound (3.5 g) obtained in the preceding step 1 in 1,4-dioxane (30 ml), bis(pinacolato)diborane (3.0 g), potassium acetate (2.9 g), and a [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane adduct (0.8 g) were added, and the mixture was stirred at 80 C. for 4 hours under a nitrogen atmosphere. After cooling, ethyl acetate was added to the reaction solution, and the insoluble matter was filtered off. The filtrate was concentrated under reduced pressure. Then, the obtained residue was purified by silica gel column chromatography (n-hexane-ethyl acetate) to obtain the title compound (3.4 g). 1H-NMR (CDCl3) delta: 1.33 (12H, s), 1.47 (9H, s), 1.79-2.08 (4H, m), 3.40 (2H, br s), 3.75-4.20 (3H, m), 6.91 (2H, d, J=7.8 Hz), 7.73 (2H, d, J=8.3 Hz).
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 80℃; for 4h;Inert atmosphere; General procedure: To a solution of the compound (3.5 g) obtained in the preceding step 1 in 1,4-dioxane (30 ml), bis(pinacolato)diborane (3.0 g), potassium acetate (2.9 g), and a [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane adduct (0.8 g) were added, and the mixture was stirred at 80 C. for 4 hours under a nitrogen atmosphere. After cooling, ethyl acetate was added to the reaction solution, and the insoluble matter was filtered off. The filtrate was concentrated under reduced pressure. Then, the obtained residue was purified by silica gel column chromatography (n-hexane-ethyl acetate) to obtain the title compound (3.4 g). 1H-NMR (CDCl3) delta: 1.33 (12H, s), 1.47 (9H, s), 1.79-2.08 (4H, m), 3.40 (2H, br s), 3.75-4.20 (3H, m), 6.91 (2H, d, J=7.8 Hz), 7.73 (2H, d, J=8.3 Hz).
  • 9
  • [ 889865-34-3 ]
  • 3-bromo-6-[(1R)-1-(3-fluorophenyl)ethoxy]imidazo[1,2-b]pyridazine [ No CAS ]
  • tert-butyl 4-[4-[6-[(1R)-1-(3-fluorophenyl)ethoxy]imidazo[1,2-b]pyridazin-3-yl]phenoxy]piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
240 mg With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; for 1h;Reflux; Inert atmosphere; Step 2 tert-Butyl 4-[4-[6-[(1R)-1-(3-fluorophenyl)ethoxy]imidazo[1,2-b]pyridazin-3-yl]phenoxy]piperidine-1-carboxylate 1,4-Dioxane (10 ml) and water (5 ml) were added to the compound (200 mg) obtained in the preceding step 1, the compound (290 mg) obtained in Reference Example 8, sodium carbonate (73 mg), and a [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane adduct (49 mg), and the mixture was heated to reflux for 1 hour under a nitrogen atmosphere. After cooling, water was added to the reaction solution, and the mixture was subjected to extraction with ethyl acetate. The extract was washed with saturated saline and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane-ethyl acetate) to obtain the title compound (240 mg). 1H-NMR (CDCl3) delta: 1.49 (9H, s), 1.68 (3H, d, J=6.4 Hz), 1.76-1.88 (2H, br m), 1.94-2.04 (2H, m), 3.35-3.43 (2H, m), 3.72-3.80 (2H, m), 4.53-4.59 (1H, m), 5.92 (1H, q, J=6.6 Hz), 6.76 (1H, d, J=9.6 Hz), 6.95-7.02 (3H, m), 7.13 (1H, dt, J=9.6, 1.8 Hz), 7.20 (1H, d, J=7.8 Hz), 7.34 (1H, td, J=7.8, 6.0 Hz), 7.62 (2H, d, J=8.7 Hz), 7.74 (1H, s), 7.83 (1H, d, J=9.6 Hz).
240 mg With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; for 1h;Inert atmosphere; Reflux; 1,4-Dioxane (10 ml) and water (5 ml) were added to the compound (200 mg) obtained in the preceding step 1, the compound (290 mg) obtained in Reference Example 8, sodium carbonate (73 mg), and a [1,1?-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane adduct (49 mg), and the mixture was heated to reflux for 1 hour under a nitrogen atmosphere. After cooling, water was added to the reaction solution, and the mixture was subjected to extraction with ethyl acetate. The extract was washed with saturated saline and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane-ethyl acetate) to obtain the title compound (240 mg). (0547) 1H-NMR (CDCl3) delta: 1.49 (9H, s), 1.68 (3H, d, J=6.4 Hz), 1.76-1.88 (2H, br m), 1.94-2.04 (2H, m), 3.35-3.43 (2H, m), 3.72-3.80 (2H, m), 4.53-4.59 (1H, m), 5.92 (1H, q, J=6.6 Hz), 6.76 (1H, d, J=9.6 Hz), 6.95-7.02 (3H, m), 7.13 (1H, dt, J=9.6, 1.8 Hz), 7.20 (1H, d, J=7.8 Hz), 7.34 (1H, td, J=7.8, 6.0 Hz), 7.62 (2H, d, J=8.7 Hz), 7.74 (1H, s), 7.83 (1H, d, J=9.6 Hz).
  • 10
  • [ 889865-34-3 ]
  • 3-bromo-6-[(1R)-1-(3-fluorophenyl)ethoxy]imidazo[1,2-b]pyridazine [ No CAS ]
  • 6-[(1R)-1-(3-Fluorophenyl)ethoxy]-3-[4-(4-piperidyloxy)phenyl]imidazo[1,2-b]pyridazine [ No CAS ]
  • 11
  • [ 308386-38-1 ]
  • [ 73183-34-3 ]
  • [ 889865-34-3 ]
YieldReaction ConditionsOperation in experiment
72% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 90℃; for 18.25h;Inert atmosphere; A mixture of 1-17 (5.0 g, 14.08 mmol), bis (pinacolato) diboron (5.36 g, 21.12 mmol) and potassium acetate (2.76 g, 28.92 mmol) in dioxane (70 mL) was degassed in a stream of argon for 30 minutes. To- this reaction mixture was added dppf PdCl2:CH2Cl2 complex (1.15 g, 1.41 mmol) , and the reaction mixture was again degassed for additional 15 minutes. The reaction mixture was stirred at 90C for 18 h. After completion of reaction, the reaction mixture was cooled to 25C, the solid was removed by filtration through a celite pad, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel (100-200 mesh size) column chromatography using 5% ethyl acetate in hexanes as eluent to give the desired product Intermediate 1-XVII (4.09, g, 72%); LCMS : m/z 348.1 [M -t-Bu +2].
72% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 90℃; for 18h;Inert atmosphere; Step II: tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]piperidine-1-carboxylate (Intermediate 1-XVII) A mixture of 1-17 (5.0 g, 14.08 mmol), bis(pinacolato)diboron (5.36 g, 21.12 mmol) and potassium acetate (2.76 g, 28.92 mmol) in dioxane (70 mL) was degassed in a stream of argon for 30 minutes. To this reaction mixture was added dppf PdCl2:CH2Cl2 complex (1.15 g, 1.41 mmol), and the reaction mixture was again degassed for additional 15 minutes. The reaction mixture was stirred at 90 C. for 18 h. After completion of reaction, the reaction mixture was cooled to 25 C., the solid was removed by filtration through a celite pad, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel (100-200 mesh size) column chromatography using 5% ethyl acetate in hexanes as eluent to give the desired product Intermediate 1-XVII (4.09 g, 72%); LCMS: m/z 348.1 [M+-t-Bu+2].
72% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 90℃; for 18h;Inert atmosphere; A mixture of 1-26 (5.0 g, 14.08 rnmol),bis(pinacolato)diboron (5.36 g, 21.12 mmol) and potassium acetate (2.76 g, 28.92 mmol) in dioxane (70 mL) was degassed in a stream of argon for 30 minutes. To this reaction mixture was added dppf.PdC12:CH2C12 complex (1.15 g, 1.41 mmol) and the reaction mixture was againdegassed for additional 15 minutes.The reaction mixture was stirred at 90C for 18 hours. After completion of the reaction, the reaction mixture was cooled to 25C, and filtered over a celite pad and the filtrate was concentrated under reduced pressure to obtain crude product, which was purified by silica gel (100-200 mesh size) columnchromatography using 5% ethyl acetate in hexanes as eluent to give the desired product Intermediate 1-XXI (4.09 g, 72%) as a white solid; LCS: m/z 348.1 [M+t3u+1]
With chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl?)]palladium(II); potassium acetate; In 1,4-dioxane; at 110℃; for 12h;Inert atmosphere; In a reaction vessel, /er/-butyl 4-(4-bromophenoxy)piperidine-l-carboxylate and Bis(pinacolato)diboron (285 mg, 1.12 mmol) were combined, followed by addition of potassium acetate (110 mg, 1.123 mmol) and XPHOS PD G2 (22 mg, 0.028 mmol). This mixture was then evacuated and backfilled with 2 (3 times). Then dry, degassed dioxane (2807 mu) was added to this flask. This mixture was then heated at 1 10C for 12 hr. The mixture was cooled, water was added and the mixture was extracted with EtOAc twice. The combined organic fractions were washed with brine, dried (anhydrous Na2S04), filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with hexane/EtOAc (0-100% gradient) to give the title compound. LC/MS [M+H]+ = 404.
With chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl?)]palladium(II); potassium acetate; In 1,4-dioxane; at 110℃; for 12h;Inert atmosphere; Reference Example 12 tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)piperidine-1-carboxylate (0319) tert-butyl 4-(4-bromophenoxy)piperidine-1-carboxylate and Bis(pinacolato)diboron (285 mg, 1.12 mmol) were combined, followed by addition of potassium acetate (110 mg, 1.123 mmol) and XPHOS PD G2 (22 mg, 0.028 mmol). This mixture was then evacuated and backfilled with N2 (3 times). Then dry, degassed dioxane (2807 mul) was added to this flask. This mixture was then heated at 110 C. for 12 hr. The mixture was cooled, water was added and the mixture was extracted with EtOAc twice. The combined organic fractions were washed with brine, dried (anhydrous Na2SO4), filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with hexane/EtOAc (0-100% gradient) to give the title compound. LC/MS [M+H]+=404

  • 12
  • [ 109384-19-2 ]
  • [ 460-00-4 ]
  • [ 889865-34-3 ]
  • 13
  • [ 889865-34-3 ]
  • [ 944407-49-2 ]
  • tert-butyl 4-[4-(2-methoxy-8-methyl-7-quinolyl)phenoxy]piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% With palladium diacetate; sodium carbonate; triphenylphosphine; In 1,4-dioxane; N,N-dimethyl-formamide; at 90℃; for 18h; j00821j Palladium acetate (0.028 g, 0.124 mmol) and triphenylphosphine (0.13 g, 0.50mmol) in dioxane (10 mL) were stirred 15 mm under an atmosphere of nitrogen. 4-[4-(4,4,5,5- tetramethyl- 1,3 ,2-dioxaborolan-2-yl)-phenoxyj -piperidine- 1 -carboxylic acid tert-butyl ester (1.00 g, 2.5 mmol), 7-bromo-8-methyl-2-methoxyquinoline (0.688 g, 2.73 mmol), DMF (10 mL) and 1 M Na2CO3 (7 mL) were added and heated at 90 C for 18 h. The mixture was concentrated, dissolved in EtOAc, washed with iN Na2CO3, water and brine, then dried (Mg504). The product was purified by ISCO (silica get, 80g column; 20-80% EtOAc/hexanes) to give a white solid (0.8 g, 72%). Analysis: LCMS m/z = 449 (M + 1). ?H NMR (CDC13) oe 7.98 (d, J = 8.8 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.35-7.3 1 (m, 2H), 7.28 (d, J = 8.3 Hz, 1H), 7.04-6.95 (m, 2H), 6.90 (d, J = 8.8 Hz, 1H), 4.54 (dquin, J = 7.1, 3.3 Hz, 1H), 4.09 (s, 3H), 3.83-3.67(m, 2H), 3.45-3.29 (m, 2H), 2.65 (s, 3H), 2.04-1.93 (m, 2H), 1.89-1.75 (m, 2H), 1.48 (s, 9H).
  • 14
  • [ 889865-34-3 ]
  • 6-bromo-5-chloroimidazo[1,2-a]pyridine [ No CAS ]
  • tert-butyl 4-[4-(5-chloroimidazo[1,2-a]pyridin-6-yl)phenoxy]piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With palladium diacetate; sodium carbonate; triphenylphosphine; In 1,4-dioxane; N,N-dimethyl-formamide; at 80℃; for 4h; Palladium acetate (0.046 g, 0.205 mmol), triphenylphosphine (0.202 g, 0.770mmol) and 1,4-dioxane (10 g, 9 mL, 100 mmol) were combined in a flask and stirred for 40 mm under nitrogen. 6-Bromo-5-chloroimidazo[1,2-ajpyridine (1.008 g, 4.35 mmol), tert-butyl 4-[4- (4,4,5,5 -tetramethyl- 1 ,3,2-dioxaborolan-2-yl)phenoxyj piperidine- 1 -carboxylate (1.514 g, 3.754 mmol), 1 M Na2CO3 in water (14.9 mL, 10 mmol) and DMF (10 g, 20 mL, 200 mmol) were then added. The reaction was purged with argon and heated at 80 C under nitrogen for 4 h. The reaction was then cooled to rt, diluted with ETOAc and washed with iN Na2CO3, and brine, then dried over sodium sulfate, filtered and concentrated. The residue was purified by Isco normal phase chromatography, eluting with EtOAc/heptane to give an off-white solid (519 mg, 70%). LC-MS: m/z = 428 (M + 1); H NMR (400 MHz, DMSO-d6) oe 8.11 (m, 1H), 7.78 (m, 1H), 7.73 (d, 1H, J= 9.2 Hz), 7.48 (m, 2H), 7.38 (d, 1H, J 9.2 Hz), 7.13 (m, 2H), 4.68 -4.64 (m, 1H), 3.74 - 3.69 (m, 2H), 3.28 - 3.20 (m, 2H), 2.01 - 1.96 (m, 2H), 1.62 - 1.54 (m, 2H), 1.44 (s, 9H).
  • 15
  • [ 889865-34-3 ]
  • [ 116355-19-2 ]
  • tert-butyl 4-[4-(5-methylimidazo[1,2-a]pyridin-6-yl)phenoxy]piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With palladium diacetate; sodium carbonate; triphenylphosphine; In 1,4-dioxane; water; N,N-dimethyl-formamide; at 20 - 80℃; for 0.8h;Inert atmosphere; Triphenylphosphine (0.702 g, 2.68 mmol) and palladium(II) acetate (0.150 g, 0.669 mmol) were placed in a pressure flask, then dissolved in 1,4-dioxane (27mL). Nitrogen gas was bubbled through the solution for several minutes, then the flask was capped and stirred at RT for 30 mm. While again bubbling N2 through the mixture, tert-butyl 4-[4-(4,4,5,5- tetramethyl- 1,3 ,2-dioxaborolan-2-yl)phenoxyj piperidine- 1 -carboxylate (5.40 g, 13.4 mmol), 6- bromo-5-methyl-imidazo[1,2-ajpyridine (2.97 g, 14.1 mmol), DMF (38 mL), and 1 M aqueous Na2CO3 solution (40.2 mmol) were added, and the flask was capped and heated to 80 C for about eight hours before the heat was turned off and the reaction was stirred at RT overnight. The mixture was concentrated, then partitioned between EtOAc and saturated aqueous NaHCO3 solution and separated. The aqueous layer was re-extracted with 100 mL of EtOAc. The organic layers were combined and washed with water (2X), then brine, then dried over Na2SO4, filtered, and concentrated. Silica gel chromatography on the ISCO (0 to 100% (20% 20:1:1 EtOH:NH4OH:H20 - 80% EtOAc) - 100 to 0% hexanes; 120 g column) yielded the desired compound as a white solid. Analysis: LCMS m/z = 408 (M + 1); ?H NMR (400 MHz, DMSOd 6) oe: 7.89 (s, 1H), 7.68 (d, J = 1.0 Hz, 1H), 7.53 (d, J = 9.0 Hz, 1H), 7.37-7.31 (m, 2H), 7.20 (d, J = 9.3 Hz, 1H), 7. 12-7.06 (m, 2H), 4.63 (tt, J = 8.0, 3.7 Hz, 1H), 3.74-3.65 (m, 2H), 3.26-3.14 (m, J = 9.5, 9.5 Hz, 2H), 2.54 (s, 3H), 2.00-1.90 (m, 2H), 1.61-1.50 (m, 2H), 1.41 (s, 9H).
  • 16
  • [ 808744-34-5 ]
  • [ 889865-34-3 ]
  • tert-butyl 4-(4-imidazo[1,2-a]pyridin-7-ylphenoxy)piperidine-1-carboxylate hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% Palladium acetate (0.021 g, 0.094 mmol) and triphenylphosphine (0.10 g, 0.38 mmol) were combined in a flask in 1,4-dioxane (6.0 mL). After stirring for 30 mi DMF (5.7 g, 6.0 mL, 78 mmol), tert-butyl 4-[4-(4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)phenoxyj piperidine- 1- carboxylate (0.75 g, 1.9 mmol), 7-bromoimidazo[1,2-ajpyridine (0.44 g, 2.2 mmol) and aq. Na2CO3 (0.5 M) (12.0 mL, 6.0 mmol) were added and the flask was heated under nitrogen at 90C overnight. The mixture was diluted with water (60 mL) then extracted with EtOAc (3x50 mL). The organic extracts were combined, washed with brine (50 mL), dried over sodium sulfate filtered and concentrated in vacuo. The residue was dissolved in EtOAc (40 mL) then treated with 2M HC1 in ether (1.5 mL) with stirring. The resultant solids were collected by filtration,
  • 17
  • [ 889865-34-3 ]
  • 7-bromo-8-ethoxyquinoline [ No CAS ]
  • 4-[4-(8-ethoxyquinolin-7-yl)phenoxy]-piperidine-1-carboxylic acid t-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% With palladium diacetate; sodium carbonate; triphenylphosphine; In 1,4-dioxane; water; N,N-dimethyl-formamide; at 85℃; for 17h;Inert atmosphere; j00442j A flask charged with 4- [4-(4,4,5 ,5 -tetramethyl- 1,3 ,2-dioxaborolan-2-yl)-phenoxyj-piperidine-1-carboxylic acid tert-butyl ester (1.62 g, 4.01 mmol), 7-bromo-8- ethoxyquinoline (1.01 g, 4.01 mmol), palladium acetate (91 mg, 0.40 mmol), triphenylphosphine (0.21 g, 0.80 mmol), 1.0 M of Na2CO3 in water (20 mL, 20 mmol), 1,4-dioxane (20 mL), and DMF (20 mL) was flashed with N2 for 15 mm. After stirred at 85 C for 17 h, the reaction wascooled to rt, and added EtOAc (100 mL), washed with sat. NaHCO3 solution (35 mL), the waterlayer was back extracted with EtOAc (50 mL). The combined organic layers were washed withH20 (35 mL), brine, dried (Na2SO4), and concentrated. The residue was chromatography onsilica gel (0-70% EtOAc/Hexanes) to give 1.21 g (67%) as yellowish gum. Analysis: ?H NMR(400 MI-Tz, DMSO-d6) oe: 8.91 - 8.95 (1 H, m), 8.35 - 8.40 (1 H, m), 7.73 - 7.78 (1 H, m), 7.56-7.62 (3 H, m), 7.51-7.56 (1 H, m), 7.07-7.13 (2 H, m), 4.59-4.69 (1 H, m), 4. 14-4.24 (2 H, m),3.66-3.76 (2 H, m), 3.13-3.28 (2 H, m), 1.91-2.02 (2H, m), 1.50-1.63 (2H, m), 1.42 (9H, s), 1.14-1.21 (3H, m).
  • 18
  • [ 889865-34-3 ]
  • 7-bromo-8-ethoxyquinoline [ No CAS ]
  • 8-ethoxy-7-[4-(piperidin-4-yloxy)phenyl]quinoline dihydrochloride [ No CAS ]
  • 19
  • [ 889865-34-3 ]
  • 7-bromo-8-(tert-butyl-dimethylsilanyloxy)quinoline [ No CAS ]
  • tert-butyl 4-[4-(8-hydroxy-7-quinolyl)phenoxy]piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
33% j00467j A flask charged with 4- [4-(4,4,5 ,5 -tetramethyl- 1,3 ,2-dioxaborolan-2-yl)-phenoxyj-piperidine-1-carboxylic acid tert-butyl ester (3.0 g, 7.44 mmol), 7-bromo-8-(tert-butyl- dimethyl- silanyloxy)-quinoline (2.77 g, 8.18 mmol), palladium acetate (170 mg, 0.75 mmol), triphenylphosphine (0.39 g, 1.49 mmol), 1.0 M of sodium carbonate in water (40 mL, 4.88 mmol), 1 ,4-dioxane (40 mL), and DMF (40 mL) was flashed with N2 for 25 mm. The reaction was stirred at 90 C for 18 h and cooled to RT. The reaction mixture was portioned between EtOAc (150 mL), washed with saturated NaHCO3 solution (100 mL), the organic layer was separated and the water layer was extracted with EtOAc (100 mL). The combined organic layers were washed with H20, brine, dried (Na2504), and concentrated. The residue was stirred in DCM (35 mL) at 0 C and added 1.0 M of tetra-n-butylammonium fluoride in THF (4.88 mL, 4.88 mmol). After 1 h at rt, the reaction was washed with H20 (20 mL), brine, dried (Na2SO4) and concentrated. The residue was chromatography on silica gel (0-70% EtOAc/Hexanes) to give (1.03 g, 33%).
  • 20
  • [ 36825-36-2 ]
  • [ 889865-34-3 ]
  • 4-[4-(4-aminoquinolin-3-yl)phenoxy]piperidine-1-carboxylic acid t-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With palladium diacetate; sodium carbonate; triphenylphosphine; In 1,4-dioxane; N,N-dimethyl-formamide; at 80℃; for 7h;Inert atmosphere; j00516j A 50 mL R. B. flask charged with 1,4-dioxane (5.00 mL), triphenylphosphine(0.0941 g, 0.359 mmol) and palladium acetate (0.0201 g, 0.0896 mmol) was stirred at rt for 15 mm under an argon atmosphere. 4- [4-(4,4,5,5 -Tetramethyl- 1 ,3,2-dioxaborolan-2-yl)-phenoxyj - piperidine-1-carboxylic acid tert-butyl ester (0.796 g, 1.97 mmol), 3-bromo-quinolin-4-ylamine (0.4 g, 2 mmol), DMF (5.00 mL) and aqueous 1M sodium carbonate (7 mL) were added and flushed with argon five times. The reaction mixture was heated at 80 C for 7 h and concentrated. The crude residue was suspended in a mixture of aqueous 1M Na2CO3 and EtOAc and then filtered through a pad of celite / silica gel, washed with EtOAc. The filtrate was separated and the aqueous layer was extracted twice with EtOAc. The combined organics was washed with brine, dried (Na2504), filtered, and evaporated to give a product that was used for the next reaction without further purification. Analysis: LCMS m/z = 420 (M + 1).
  • 21
  • [ 889865-34-3 ]
  • [ 623-00-7 ]
  • [ 943636-62-2 ]
YieldReaction ConditionsOperation in experiment
90% With palladium diacetate; sodium carbonate; triphenylphosphine; In 1,4-dioxane; N,N-dimethyl-formamide; at 80℃; for 7h;Inert atmosphere; j00534j A 50 niL R. B. flask charged with 1,4-dioxane (4.00 mL), triphenylphosphine(0.0607 g, 0.23 1 mmol), and palladium acetate (0.0130 g, 0.0578 mmol) was stirred at rt for 15 mm under an argon atmosphere. 4-[4-(4,4,5,5 -Tetramethyl- 1 ,3,2-dioxaborolan-2-yl)-phenoxyj - piperidine-1-carboxylic acid t-butyl ester (0.6 g, 1 mmol), 4-bromobenzonitrile (0.210 g, 1.16 mmol), DMF(4.00 mL), and 1M aqueous Na2CO3 (4 mL) were added and flushed with argon five times. The reaction mixture was heated at 80 C for 7 h and concentrated. The residue was suspended in a mixture of aqueous 1 M Na2CO3 and EtOAc and then filtered through a pad of celite / silica gel. The filtrate was separated into two layers and the aqueous layer was extracted twice with EtOAc. The combined organics was washed with brine, dried, filtered, and evaporated to give a crude product that was purified by silica gel column chromatography (80 g ISCO column, using 0 to 40% EtOAc in hexane) to give 0.5 g (90%). Analysis: LCMS m/z = 379 (M+1); ?H NMR (400 MHz, CHLOROFORM-d) oe: 7.60-7.74 (m, 4H), 7.53 (d, J = 8.8 Hz, 2H), 6.98-7.04 (m, 2H), 4.50-4.58 (m, 1H), 3.65-3.77 (m, 2H), 3.32-3.42 (m, 2H), 1.89-2.01 (m, 2H), 1.73-1.84 (m, 2H), 1.44-1.51 (m, 11H).
  • 22
  • [ 889865-34-3 ]
  • trifluoromethanesulfonic acid 7-bromoquinolin-8-yl ester [ No CAS ]
  • 4-[4-(8-trifluoromethanesulfonyloxyquinolin-7-yl)-phenoxy]piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With palladium diacetate; sodium carbonate; triphenylphosphine; In 1,4-dioxane; water; at 85℃; for 1.5h;Inert atmosphere; j00630j A flask charged with 4- [4-(4,4,5 ,5-tetramethyl- 1 ,3,2-dioxaborolan-2-yl)- phenoxyj-piperidine-1-carboxylic acid tert-butyl ester (5 g, 10 mmol) , trifluoromethanesulfonic acid 7-bromo-quinolin-8-yl ester (4.86 g, 13.6 mmol), palladium acetate (280 mg, 1.2 mmol), triphenylphosphine (0.65 g, 2.5 mmol), 1,4-dioxane (60 mL) and 1.0 M of Na2CO3 in H20 (62.0 mL, 62.0 mmol) was flashed with nitrogen for 5 mm. The reaction was heated at 85 C for 1.5 h. After cooling to room temp, the reaction was diluted with EtOAc (200 mL), washed with an aq. sat. NaHCO3 solution (100 mL). The water layer was back-extracted with EtOAc (2 x 50 mL). The combined organic layers was washed with brine (50 mL), dried (Na2SO4), and concentrated. The cmde was purified by silica gel chromatography (0-50% EtOAc/hexanes) to give 4- [4-(8-trifluoromethanesulfonyloxy-quinolin-7-yl)-phenoxyj -piperidine- 1 -carboxylic acid tert-butyl ester as a white solid (5 g; 60%); Analysis: LCMS mlz = 553 (M + 1); ?H NMR (400 MHz, CDC13) oe: 9.06 - 9.10 (m, 1 H), 8.20 - 8.28 (m, 1 H), 7.87 (d, J8.53 Hz, 1 H), 7.62 (d, J=8.53 Hz, 1 H), 7.50 - 7.56 (m, 3 H), 7.05 (d, J9.03 Hz, 2 H), 4.48 - 4.63 (m, 1 H), 3.69 - 3.80 (m, 2 H), 3.29 - 3.44 (m, 2 H), 1.92 - 2.03 (m, 2 H), 1.75 - 1.85 (m, 2 H), 1.48 (s, 9 H).
  • 23
  • [ 889865-34-3 ]
  • 5-chloro-6-[4-(4-piperidyloxy)phenyl]imidazo[1,2-a]pyridine [ No CAS ]
  • 24
  • [ 889865-34-3 ]
  • N-ethyl-4-[4-(8-methyl-7-quinolyl)phenoxy]piperidine-1-carboxamide [ No CAS ]
  • 25
  • [ 889865-34-3 ]
  • 8-methyl-7-[4-(piperidin-4-yloxy)phenyl]quinoline dihydrochloride [ No CAS ]
  • 26
  • [ 889865-34-3 ]
  • N,N-dimethyl-4-[4-(8-methyl-7-quinolyl)phenoxy]piperidine-1-carboxamide hydrochloride [ No CAS ]
  • 27
  • [ 889865-34-3 ]
  • ethyl 4-[4-(8-methyl-7-quinolyl)phenoxy]piperidine-1-carboxylate [ No CAS ]
  • 28
  • [ 889865-34-3 ]
  • N-methoxy-4-[4-(8-methyl-7-quinolyl)phenoxy]piperidine-1-carboxamide [ No CAS ]
  • 29
  • [ 889865-34-3 ]
  • 1-{4-[4-(4-aminoquinolin-3-yl)phenoxy]piperidin-1-yl}propan-1-one [ No CAS ]
  • 30
  • [ 889865-34-3 ]
  • 4-{4-[4-(2,2,2-trifluoroacetylamino)quinolin-3-yl]phenoxy}piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]
  • 31
  • [ 889865-34-3 ]
  • C25H24F3N3O3 [ No CAS ]
  • 32
  • [ 889865-34-3 ]
  • 4’-(piperidin-4-yloxy)biphenyl-4-carbonitrile [ No CAS ]
  • 33
  • [ 889865-34-3 ]
  • 4’-[1-((R)-tetrahydrofuran-2-carbonyl)piperidin-4-yloxy]biphenyl-4-carbonitrile [ No CAS ]
  • 34
  • [ 889865-34-3 ]
  • tert-butyl 4-[4-[8-(dimethylamino)-7-quinolyl]phenoxy]piperidine-1-carboxylate [ No CAS ]
  • 35
  • [ 889865-34-3 ]
  • tert-butyl 4-[4-(8-cyano-7-quinolyl)phenoxy] piperidine-1-carboxylate [ No CAS ]
  • 36
  • [ 889865-34-3 ]
  • 7-[4-(4-piperidyloxy)phenyl] quinoline-8-carboxamide 2,2,2-trifluoroacetic acid [ No CAS ]
  • 37
  • [ 889865-34-3 ]
  • 2,2,2-trifluoro-1-{4-[4-(8-methylquinolin-7-yl)phenoxy]piperidin-1-yl}ethanone [ No CAS ]
  • 38
  • [ 889865-34-3 ]
  • 1-{4-[4-(6-phenyl-pyridin-3-yl)phenoxy]piperidin-1-yl}-propan-1-one trifluoroacetate [ No CAS ]
  • 39
  • [ 889865-34-3 ]
  • 2-methyl-1-{4-[4-(6-phenylpyridin-3-yl)phenoxy]piperidin-1-yl}propan-1-one [ No CAS ]
  • 40
  • [ 889865-34-3 ]
  • 5-[4-(piperidin-4-yloxy)phenyl]-1H-pyrrolo[2,3-b]pyridine [ No CAS ]
  • 41
  • [ 889865-34-3 ]
  • 1-{4-[4-(1H-pyrrolo[2,3-b]pyridin-5-yl)-phenoxy]piperidin-1-yl}propan-1-one hydrochloride [ No CAS ]
  • 42
  • [ 889865-34-3 ]
  • N-isopropoxy-4-[4-(8-methyl-7-quinolyl)phenoxy]piperidine-1-carboxamide [ No CAS ]
  • 43
  • [ 889865-34-3 ]
  • N-butyl-4-[4-(5-chloroimidazo[1,2-a]pyridin-6-yl)phenoxy]piperidine-1-carboxamide [ No CAS ]
  • 44
  • [ 889865-34-3 ]
  • 5-methyl-7-(4-(piperidin-4-yloxy)phenyl)quinoline [ No CAS ]
  • 45
  • [ 889865-34-3 ]
  • 2-phenyl-5-[4-(piperidin-4-yloxy)-phenyl]-pyridine [ No CAS ]
  • 46
  • [ 889865-34-3 ]
  • [ 183208-35-7 ]
  • 4-[4-(1H-pyrrolo[2,3-b]pyridin-5-yl)phenoxy]piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With palladium diacetate; sodium carbonate; triphenylphosphine; In N,N-dimethyl-formamide; at 80℃; for 18h;Inert atmosphere; j00285j Palladium acetate (0.0111 g, 0. 0496 mmol) and triphenylphosphine (0.0520 g, 0.198 mmol) were stirred 15 mm under an atmosphere of nitrogen. 4-[4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-phenoxyj -piperidine- 1 -carboxylic acid tert-butyl ester (0.40 g, 0.99 mmol), 5-bromo-1H-pyrrolo[2,3-bjpyridine (0.235 g, 1.19 mmol), DMF (4 mL) and 1 M Na2CO3 (4 mL) were added and heated at 80 C for 18 h. The mixture was concentrated, dissolved in EtOAc, washed with iN Na2CO3, water and brine, then dried (Mg504). The product was purified by ISCO (silica get, 80g column; 40-80% EtOAc/hexanes) to give a white solid (0.25 g,64%). Analysis: LCMS m/z = 394 (M + 1): ?H NMR (CDC13) oe 9.16 (br. 5., 1H), 8.51 (d, J = 2.0 Hz, 1H), 8.07 (d, J = 2.0 Hz, 1H), 7.47-7.61 (m, 2H), 7.30-7.38 (m, 1H), 6.99-7.10 (m, 2H), 6.55 (dd, J = 3.4, 1.9 Hz, 1H), 4.52 (dt, J = 7.1, 3.6 Hz, 1H), 3.69-3.80 (m, 2H), 3.31-3.46 (m, 2H), 1.93-2.00 (m, 2H), 1.76-1.84 (m, 2H), 1.48 (s, 9H).
  • 47
  • 5-bromo-7-methylquinoline [ No CAS ]
  • [ 889865-34-3 ]
  • tert-butyl 4-(4-(5-methylquinolin-7-yl)phenoxy)piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 100℃; for 15h; To a degassed solution of 4- [4-(4,4,5 ,5-tetramethyl- [1,3,21 dioxaborolan-2-yl)- phenoxyj-piperidine-1-carboxylic acid tert-butyl ester (1 eq.), 5-Bromo-7-methylquinoline (1 eq.) and sodium carbonate (2.6 eq.) in dioxane / water (3:1), was added tetrakis-(triphenylphosphino)palladium (13 mg, 0.012 mmol) and the reaction mixture was heated at 100 C for 1 5h when TLC confirmed completion of reaction. The reaction was filtered through a bed of Celite and the filtrate was diluted with ethyl acetate and washed with water. The combined organic phases was concentrated to get the crude product was purified by column chromatography using silica gel and 3 0-40% EtOAc/hexane as eluent to afford tert-butyl 4-(4-(5- methylquinolin-7-yl)phenoxy)piperidine- 1 -carboxylate (64%). Analysis: LCMS (ESI): 419 (M+1); ?H NMR (400 MHz, DMSO-d6) 3: 8.86 (d, J 4.2 Hz, 1H), 8.15 (d, J 8.6 Hz, 1H), 7.81 (s, 1H), 7.47-7.34 (m, 4H), 7.13 (d, J= 8.4 Hz, 2H), 4.64 (m, 1H), 3.75-3.61 (m, 2H), 3.21 (m, 2H), 2.55 (s, 3H), 1.97 (m, 2H), 1.64-1.50 (m, 2H), 1.41 (s, 9H).
  • 48
  • 7-bromo-8-methyl-quinoline [ No CAS ]
  • [ 889865-34-3 ]
  • 4-[4-(8-methyl-quinolin-7-yl)-phenoxy]-piperidine-1-carboxylic acid t-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 80℃;Inert atmosphere; 4- [4-(4,4,5 ,5 -Tetramethyl- 1,3 ,2-dioxaborolan-2-yl)-phenoxyj -piperidine- 1-carboxylic acid tert-butyl ester (1.01 g, 2.51 mmol), 7-bromo-8-methylquinoline (0.556 g, 2.50 mmol), tetrakis(triphenylphosphine)palladium(0) (0.123 g, 0.106 mmol) and K2C03 (0.556 g, 4.02 mmol) were combined in water (6.0 mL): 1,4-dioxane (24.0 mL). The mixture was briefly vacuum degassed then stirred at 80 C under an atmosphere of nitrogen overnight. The mixture was cooled, partitioned between EtOAc (100 mL) and water (20 mL) and the layers wee separated. The aqueous layer was extracted with EtOAc (50 mL) and the combined organics were washed with brine (50 mL), dried over sodium sulfate and filtered through 2 mL silica gel. The filtrate was concentrated in vacuo to afford 4-[4-(8-methyl-quinolin-7-yl)-phenoxyj- piperidine- 1 -carboxylic acid t-butyl ester.
  • 49
  • [ 889865-34-3 ]
  • [ 27012-25-5 ]
  • 4-[4-(6-phenylpyridin-3-yl)-phenoxy]-piperidine-1-carboxylic acid t-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; at 100℃; for 0.0833333h;Schlenk technique; Inert atmosphere; To a schlenck flask was added 4-[4-(4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)-phenoxyj-piperidine-1-carboxylic acid t-butyl ester (0.5 g, 1.24 mmol), 5-bromo-2-phenyl- pyridine (0.44 g, 1.86 mmol), tetrakis(triphenylphosphine)palladium(0) (0.14 g, 0.12 mmol), iN sodium carbonate (3.72 mL, 3.72 mmol), followed by 1,4-dioxane (10 mL) and was degassed under an atmosphere of argon for 5 mm and was heated at 100 C overnight. The reaction was cooled, filtered through a pad of celite, washed with iN sodium carbonate, water, brine, dried over sodium sulfate, and concentrated. The product was purified via silica gel chromatography (10-30% EtOAc/hexanes) and concentrated was isolated (0.48 g, 90%). Analysis: LCMS m/z = 431 (M+1).
  • 50
  • [ 876343-09-8 ]
  • [ 889865-34-3 ]
  • tert-butyl 4-(4-(4-chloro-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenoxy)piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
542 mg With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In water; acetonitrile; at 100℃; for 2h; In a 100 ml round bottom flask, purged and maintained under inert atmosphere were added 4- chloro-6-iodo-7-(phenylsulfonyl)-7/-/-pyrrolo[2,3-d]pyrimidine (intermediate 2) (400 mg, 0.954 mmol), fe/f-butyl 4-(4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)phenoxy)piperidine-1 - carboxylate (CAS 889865-34-3) (385 mg, 0.954 mmol), K2C03 (289 mg, 2.1 mmol) and PdCI2(PPh3)2 (70 mg, 0.0954 mmol). Then, ACN (12 ml) and H20 (3 ml) were added and the mixture was stirred at 100C for 2 h. The mixture was filtered and the filtrate was concentrated. The residue was extracted with EtOAc (30 ml), the organic layer was washed with water and brine, dried over Na2S04 and concentrated under reduced pressure to afford 542 mg of the title compound. LC-MS (method I): Rt = 2.28 min, [M+H]+ = 570.
  • 51
  • [ 876343-10-1 ]
  • [ 889865-34-3 ]
  • tert-butyl 4-(4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenoxy)piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
1.039 g With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 3h;Inert atmosphere; A mixture of <strong>[876343-10-1]4-chloro-6-iodo-7H-pyrrolo[2,3-d]pyrimidine</strong> (Synnovator, Inc., CAS[ 876343-10-1]) (855 mg, 3.06 mmol), Cs2C03 (2492 mg, 7.65 mmol) and tert-butyl 4-(4-(4,4,5,5-tetramethyl- 1 ,3, 2-dioxaborolan-2-yl)phenoxy)piperidine-1 -carboxylate (step 1) (1234 mg, 3.06 mmol) in dioxane/water 1 :1 (30 ml) was degassed with argon. PdCl2(dppf)-CH2Cl2 adduct (250 mg, 0.306 mmol) was added and the RM was stirred at 100C for 3 h. The RM was cooled to RT and then partitioned between EtOAc and sat. aq. NaHC03. Layers were separated, then the organic layer was washed with brine, dried over MgS04 and concentrated under reduced pressure. Purification of the crude product by flash chromatography on silica gel eluting with 0 - 100% EtOAc in CHX afforded a brown residue. The residue was then triturated with MeOH, the resulting suspension was filtered, washed with Et20 and dried under reduced pressure to afford 1.039 g of the title compound as a beige powder. LC-MS (Method A): Rt = 1.24 min, [M+H]+ = 429.3/431.2.
  • 52
  • [ 889865-34-3 ]
  • tert-butyl 4-(2-(4-(4-(4-(5-fluoro-3-((3R,4S)-3-hydroxy-4-isobutylpyrrolidine-1-carboxamido)-2-methylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenoxy)piperidin-1-yl)ethyl)piperidine-1-carboxylate [ No CAS ]
  • 53
  • [ 889865-34-3 ]
  • (x)C2HF3O2*C40H52FN7O3 [ No CAS ]
  • 54
  • [ 889865-34-3 ]
  • (3R,4S)-N-(3-(6-(4-((1-(2-(1-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-methoxybenzoyl)piperidin-4-yl)ethyl)piperidin-4-yl)oxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-3-hydroxy-4-isobutylpyrrolidine-1-carboxamide [ No CAS ]
  • 55
  • [ 889865-34-3 ]
  • C33H39FN6O3*(x)ClH [ No CAS ]
  • 56
  • [ 889865-34-3 ]
  • tert-butyl 4-((4-(4-(4-(5-fluoro-3-((3R,4S)-3-hydroxy-4-isobutylpyrrolidine-1-carboxamido)-2-methylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenoxy)piperidin-1-yl)methyl)piperidine-1-carboxylate [ No CAS ]
  • 57
  • [ 889865-34-3 ]
  • tert-butyl 4-(2-(4-(4-(4-(5-fluoro-3-((3R,4S)-3-hydroxy-4-isobutylpyrrolidine-1-carboxamido)-2-methylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenoxy)piperidin-1-yl)ethoxy)piperidine-1-carboxylate [ No CAS ]
  • 58
  • [ 889865-34-3 ]
  • (x)C2HF3O2*C40H52FN7O4 [ No CAS ]
  • 59
  • [ 889865-34-3 ]
  • (3R,4S)-N-(3-(6-(4-((1-(2-((1-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-methoxybenzoyl)piperidin-4-yl)oxy)ethyl)piperidin-4-yl)oxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-3-hydroxy-4-isobutylpyrrolidine-1-carboxamide [ No CAS ]
  • 60
  • [ 889865-34-3 ]
  • tert-butyl 4-(4-(4-(5-fluoro-3-((3R,4S)-3-hydroxy-4-isobutylpyrrolidine-1-carboxamido)-2-methylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenoxy)piperidine-1-carboxylate [ No CAS ]
  • 61
  • [ 889865-34-3 ]
  • (x)C2HF3O2*C33H39FN6O3 [ No CAS ]
  • 62
  • [ 889865-34-3 ]
  • [ 1706749-51-0 ]
  • [ 2633634-33-8 ]
YieldReaction ConditionsOperation in experiment
112 mg With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In water; acetonitrile at 100℃; for 1.5h; Inert atmosphere; 2.2 Step 2: tert-butyl 4-(4-(2-methyl-1-oxo-1,2-dihydro-2,7-naphthyridin-4- yl)phenoxy)piperidine-1-carboxylate To a 25 ml vial were added under an argon atmosphere tert-butyl 4-(4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)piperidine-1-carboxylate (264 mg, 0.511 mmol), 4-bromo-2-methyl-2,7-naphthyridin-1(2H)-one (intermediate 5, 123 mg, 0.511 mmol), K2CO3 (212 mg, 1.532 mmol), ACN (4 ml) and water (1 ml). Solid PdCl2(dppf) (37 mg, 0.051 mmol) was added and the RM was stirred at 100 °C for 1.5 h. The mixture was cooled to RT, filtered through CELITE, the filtrate was concentrated and the residue purified by reversed phase chromatography on a REDISEP Gold HP C18 column (15.5 g) eluting with ACN (from 2 % to 100 %) in an aq. solution of TFA (0.1 %), yielding the title compound as a solid (112 mg). Method D: Rt = 0.49 min; [M+H]+= 336.
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