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[ CAS No. 89488-25-5 ] {[proInfo.proName]}

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Chemical Structure| 89488-25-5
Chemical Structure| 89488-25-5
Structure of 89488-25-5 * Storage: {[proInfo.prStorage]}
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Product Details of [ 89488-25-5 ]

CAS No. :89488-25-5 MDL No. :MFCD06659863
Formula : C6H6BClO3 Boiling Point : -
Linear Structure Formula :- InChI Key :GGZASRFCRAZNPO-UHFFFAOYSA-N
M.W : 172.37 Pubchem ID :23005362
Synonyms :

Calculated chemistry of [ 89488-25-5 ]

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.0
Num. rotatable bonds : 1
Num. H-bond acceptors : 3.0
Num. H-bond donors : 3.0
Molar Refractivity : 43.3
TPSA : 60.69 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -6.18 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.0
Log Po/w (XLOGP3) : 1.65
Log Po/w (WLOGP) : -0.27
Log Po/w (MLOGP) : 0.27
Log Po/w (SILICOS-IT) : -0.55
Consensus Log Po/w : 0.22

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.29
Solubility : 0.893 mg/ml ; 0.00518 mol/l
Class : Soluble
Log S (Ali) : -2.54
Solubility : 0.5 mg/ml ; 0.0029 mol/l
Class : Soluble
Log S (SILICOS-IT) : -1.32
Solubility : 8.16 mg/ml ; 0.0473 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.72

Safety of [ 89488-25-5 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H312-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 89488-25-5 ]

* 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 [ 89488-25-5 ]

[ 89488-25-5 ] Synthesis Path-Downstream   1~85

  • 1
  • [ 89466-08-0 ]
  • [ 89488-25-5 ]
YieldReaction ConditionsOperation in experiment
With chlorine In acetic acid
  • 2
  • [ 89488-25-5 ]
  • [ 78607-36-0 ]
  • [ 1018687-75-6 ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate In water; acetonitrile at 20 - 80℃; The title compound was prepared using methods analogous to those in Representative Procedure A. 1H NMR (500 MHz, CDCl3, δ): 8.41 (dd, J=4.8, 1.9 Hz, 1H), 7.73 (dd, J=7.5, 1.9 Hz, 1H), 7.35 (dd, J=7.5, 4.8 Hz, 1H), 7.29 (dd, J=8.7, 2.6 Hz, 1H), 7.19 (d, J=2.6 Hz, 1H), 6.95 (d, J=8.7 Hz, 1H), 6.05 (br s, 1H); 13C NMR (126 MHz, CDCl3, δ): 157.8, 150.7, 149.1, 140.9, 132.4, 130.4, 130.1, 125.8, 125.74, 122.6, 117.7; HRMS (ESI+): calculated for C11H8Cl2NO [M+H+], 239.9977; m/z found, 239.9976.
  • 3
  • [ 89488-25-5 ]
  • [ 703-61-7 ]
  • [ 956125-03-4 ]
YieldReaction ConditionsOperation in experiment
22% With sodium carbonate In water; toluene for 15h; Reflux; Inert atmosphere; 37 4-Chloro-2-(4-chloro-quinolin-2-yl)-phenol 2,4-Dichloroquinoline (0.29 g, 1.5 mmol), 2-hydroxy-5-chloro boronic acid (0.24 g, 1.44 mmol), sodium carbonate (0.31 g, 3 mmol) and palladium tetrakistriphenylphosphine (0.086 g, 0.075 mmol) were suspended in a previously degassed mixture of toluene (3 mL) and water (1 mL). The reaction mixture was refluxed under nitrogen for 15 hours and allowed to cool to room temperature. The contents of the flask were dissolved in ethyl acetate (100 mL) and water (100 mL) and the layers were separated. The aqueous layer was extracted with another portion of ethyl acetate (100 mL), the organics were combined, washed with water (100 mL) and brine (100 mL), dried with magnesium sulfate, filtered, and evaporated to give a pale red solid. The solid was triturated with ethyl acetate to give a yellow solid. Yield: 100 mg, 22%. Analytical LCMS method 2 retention time 7.91 min, M+H=290.
  • 4
  • [ 956124-96-2 ]
  • [ 89488-25-5 ]
  • [ 956124-97-3 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate In water; toluene; butan-1-ol for 48h; Heating; 27 {(R)-2-[2-(5-Chloro-2-hydroxy-phenyl)-pyrimidin-4-ylamino]-1-methyl-ethyl}-carbamic acid benzyl ester (5-Chloro-2-hydroxyphenyl)boronic acid (0.6 mmol, 0.1 g) and palladium tetrakistriphenylphosphine (0.01 mmol, 0.011 g) were weighed into a tube and placed under a nitrogen atmosphere. A previously de-gassed sodium carbonate solution (2 M, 1 mL) was added. (R)-2-(2-Chloro-pyrimidin-4-ylamino)-1-methyl-ethyl]-carbamic acid benzyl ester (0.2 mmol, 0.06 g) was dissolved in a de-gassed mixture of toluene (1 mL) and butanol (1 mL) and added to the other reagents. The reaction mixture was heated to 10° C. for 48 hours. The reaction mixture was allowed to cool to room temperature, water was added in a test tube, a small amount of ethyl acetate was added, and the organic layer was decanted off and filtered through a plug of silica and eluted with ethyl acetate. The solvent was removed under reduced pressure to yield the crude material. Analytical LCMS method 1, retention time 5.01 min, M+H=413. The product was used in the next step without further purification.
  • 5
  • [ 35450-36-3 ]
  • [ 89488-25-5 ]
  • [ 1238196-95-6 ]
YieldReaction ConditionsOperation in experiment
89% With tetrakis(triphenylphosphine) palladium(0); water; caesium carbonate In 1,2-dimethoxyethane at 125℃; for 0.25h; Inert atmosphere; Microwave irradiation; Combinatorial reaction / High throughput screening (HTS);
  • 6
  • [ 89488-25-5 ]
  • [ 1354787-45-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 18 h / 70 °C / Inert atmosphere 2.1: potassium carbonate / N,N-dimethyl-formamide / 0.17 h / 20 °C / Inert atmosphere 2.2: 18 h / 60 °C 3.1: potassium carbonate; tetra(n-butyl)ammonium hydroxide / tri tert-butylphosphoniumtetrafluoroborate; bis({5-chloro-2-[(4-chlorophenyl)(hydroxyimino)methyl]phenyl})cyclodipalladachl-orane-1,3,4-tris(ylium)-2-uide / N,N-dimethyl-formamide; methanol / 3 h / 130 °C / Microwave irradiation; Sealed tube 4.1: hydrogen / 10 wt% Pd(OH)2 on carbon / ethanol / 18 h / 60 °C / 2585.81 Torr 5.1: potassium carbonate / dimethyl sulfoxide / 18 h / 20 °C
  • 7
  • [ 89488-25-5 ]
  • [ 1354786-47-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 18 h / 70 °C / Inert atmosphere 2.1: potassium carbonate / N,N-dimethyl-formamide / 0.17 h / 20 °C / Inert atmosphere 2.2: 18 h / 60 °C 3.1: potassium carbonate; tetra(n-butyl)ammonium hydroxide / tri tert-butylphosphoniumtetrafluoroborate; bis({5-chloro-2-[(4-chlorophenyl)(hydroxyimino)methyl]phenyl})cyclodipalladachl-orane-1,3,4-tris(ylium)-2-uide / N,N-dimethyl-formamide; methanol / 3 h / 130 °C / Microwave irradiation; Sealed tube 4.1: hydrogen / 10 wt% Pd(OH)2 on carbon / ethanol / 18 h / 60 °C / 2585.81 Torr 5.1: potassium carbonate / dimethyl sulfoxide / 2 h / 20 °C 6.1: hydrogenchloride / 1,4-dioxane; methanol / 3 h / 20 °C
  • 8
  • [ 89488-25-5 ]
  • [ 1354787-42-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 18 h / 70 °C / Inert atmosphere 2.1: potassium carbonate / N,N-dimethyl-formamide / 0.17 h / 20 °C / Inert atmosphere 2.2: 18 h / 60 °C 3.1: potassium carbonate; tetra(n-butyl)ammonium hydroxide / tri tert-butylphosphoniumtetrafluoroborate; bis({5-chloro-2-[(4-chlorophenyl)(hydroxyimino)methyl]phenyl})cyclodipalladachl-orane-1,3,4-tris(ylium)-2-uide / N,N-dimethyl-formamide; methanol / 3 h / 130 °C / Microwave irradiation; Sealed tube 4.1: hydrogen / 10 wt% Pd(OH)2 on carbon / ethanol / 18 h / 60 °C / 2585.81 Torr 5.1: potassium carbonate / dimethyl sulfoxide / 2 h / 20 °C
  • 9
  • [ 89488-25-5 ]
  • [ 1354786-52-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 18 h / 70 °C / Inert atmosphere 2.1: potassium carbonate / N,N-dimethyl-formamide / 0.17 h / 20 °C / Inert atmosphere 2.2: 18 h / 60 °C 3.1: potassium carbonate; tetra(n-butyl)ammonium hydroxide / tri tert-butylphosphoniumtetrafluoroborate; bis({5-chloro-2-[(4-chlorophenyl)(hydroxyimino)methyl]phenyl})cyclodipalladachl-orane-1,3,4-tris(ylium)-2-uide / N,N-dimethyl-formamide; methanol / 3 h / 130 °C / Microwave irradiation; Sealed tube 4.1: hydrogen / 10 wt% Pd(OH)2 on carbon / ethanol / 18 h / 60 °C / 2585.81 Torr 5.1: potassium carbonate / dimethyl sulfoxide / 20 h / 20 °C 6.1: hydrogenchloride / 1,4-dioxane / 20 h / 20 °C
  • 10
  • [ 89488-25-5 ]
  • [ 1354787-52-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 18 h / 70 °C / Inert atmosphere 2.1: potassium carbonate / N,N-dimethyl-formamide / 0.17 h / 20 °C / Inert atmosphere 2.2: 18 h / 60 °C 3.1: potassium carbonate; tetra(n-butyl)ammonium hydroxide / tri tert-butylphosphoniumtetrafluoroborate; bis({5-chloro-2-[(4-chlorophenyl)(hydroxyimino)methyl]phenyl})cyclodipalladachl-orane-1,3,4-tris(ylium)-2-uide / N,N-dimethyl-formamide; methanol / 3 h / 130 °C / Microwave irradiation; Sealed tube 4.1: hydrogen / 10 wt% Pd(OH)2 on carbon / ethanol / 18 h / 60 °C / 2585.81 Torr 5.1: potassium carbonate / dimethyl sulfoxide / 20 h / 20 °C
  • 11
  • [ 89488-25-5 ]
  • [ 1354787-46-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 18 h / 70 °C / Inert atmosphere 2.1: potassium carbonate / N,N-dimethyl-formamide / 0.17 h / 20 °C / Inert atmosphere 2.2: 18 h / 60 °C 3.1: potassium carbonate; tetra(n-butyl)ammonium hydroxide / tri tert-butylphosphoniumtetrafluoroborate; bis({5-chloro-2-[(4-chlorophenyl)(hydroxyimino)methyl]phenyl})cyclodipalladachl-orane-1,3,4-tris(ylium)-2-uide / N,N-dimethyl-formamide; methanol / 3 h / 130 °C / Microwave irradiation; Sealed tube 4.1: hydrogen / 10 wt% Pd(OH)2 on carbon / ethanol / 18 h / 60 °C / 2585.81 Torr
  • 12
  • [ 89488-25-5 ]
  • [ 1354787-47-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 18 h / 70 °C / Inert atmosphere 2.1: potassium carbonate / N,N-dimethyl-formamide / 0.17 h / 20 °C / Inert atmosphere 2.2: 18 h / 60 °C 3.1: potassium carbonate; tetra(n-butyl)ammonium hydroxide / tri tert-butylphosphoniumtetrafluoroborate; bis({5-chloro-2-[(4-chlorophenyl)(hydroxyimino)methyl]phenyl})cyclodipalladachl-orane-1,3,4-tris(ylium)-2-uide / N,N-dimethyl-formamide; methanol / 3 h / 130 °C / Microwave irradiation; Sealed tube
  • 13
  • [ 89488-25-5 ]
  • [ 1354787-48-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 18 h / 70 °C / Inert atmosphere 2.1: potassium carbonate / N,N-dimethyl-formamide / 0.17 h / 20 °C / Inert atmosphere 2.2: 18 h / 60 °C
  • 14
  • [ 1197294-80-6 ]
  • [ 89488-25-5 ]
  • [ 1235407-20-1 ]
YieldReaction ConditionsOperation in experiment
66% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 70℃; for 18h;Inert atmosphere; <strong>[1197294-80-6]tert-Butyl 4-(4-bromopyridin-2-yl)piperazine-1-carboxylate</strong> (1.00 g, 2.66 mmol), 5-chloro-2-hydroxyphenylboronic acid (458 mg, 2.66 mmol) and sodium carbonate (1.13 g, 10.64 mmol) were combined and dissolved in a mixture of dioxane/water (14 mL/4 mL). The reaction mixture was degassed for 20 min with nitrogen and then tetrakistriphenylphosphinepalladium (0) (153 mg, 0.133 mmol) was added. The reaction mixture was heated at 70 C. for 18 hours and then partitioned between ethyl acetate (20 mL) and water (10 mL). The organic layer was separated, washed with brine (10 mL), dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was purified on silica gel by Biotage (10% to 60% ethyl acetate in heptane over 20 CV) to give the title compound (700 mg, 66%) as a white solid.1H NMR (400 MHz, CD3OD): delta 1.40 (s, 9H), 3.50 (s, 8H), 6.80-6.90 (m, 2H), 6.95 (s, 1H), 7.15 (d, 1H), 7.30 (s, 1H), 8.05 (d, 1H).LCMS Rt=2.48 minutes MS m/z 388 [M-H]-.
  • 15
  • [ 3934-20-1 ]
  • [ 89488-25-5 ]
  • [ 1207535-01-0 ]
YieldReaction ConditionsOperation in experiment
7% With sodium carbonate In 1,2-dimethoxyethane; water at 85℃; for 4h; Inert atmosphere; 1 A mixture of 2,4-dichloropyrimidine (0.765 g, 5.03 mmol), (5-chloro-2- hydroxyphenyl)boronic acid (0.568 g, 3.30 mmol), 2.0 M aqueous sodium carbonate (2.82 mL, 5.64 mmol), and 1 ,2-dimethoxyethane (8 mL) was sparged for 10 minutes with argon. Tetrakis(triphenylphosphine)palladium(0) (0.217 g, 0.19 mmol) was added, and the resultant mixture was heated for 4 hours at 85 °C. The reaction mixture mixture was cooled to 0 °C, quenched with saturated aqueous ammonium chloride solution, and extracted with dichloromethane (x 3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by automated silica gel flash chromatography (hexanes to ethyl acetate gradient elution) to afford the title compound as a yellow solid (61 .5 mg, 7%). 1 HNMR (de-DMSO): δ 7.06 (d, 1 H), 7.45 (m, 1 H), 8.00 (d, 1 H), 8.28 (d, 1 H), 8.81 (d, 1 H), 1 1 .21 (s, 1 H).LCMS Rt = 1 .74 min MS m/z 241 [MH]+
  • 16
  • [ 19798-80-2 ]
  • [ 89488-25-5 ]
  • [ 1235406-61-7 ]
YieldReaction ConditionsOperation in experiment
82% With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,2-dimethoxyethane; ethanol; water at 100℃; for 14h; Inert atmosphere; 22 2-(2-aminopyridin-4-yl)-4-chlorophenol EXAMPLE 22 Preparation of (S)-6-((l -amino- l-oxopropan-2-yl)amino)-2-(2-(2- aminopyridin-4-yl)-4-chlorophenoxy)pyrimidine-4-carboxamide (Cpd No. 67) Scheme 47 2-(2-aminopyridin-4-yl)-4-chlorophenol: A mixture of 4-chloro-2-aminopyridine (1.28 g, 10 mmol), boronic acid (1.72 g, 10 mmol), Na2C03 (3.18g, 30mmol) and Pd(PPh3)2Cl2 in DME/EtOH/H20 (4mL/2mL/4mL) was purged with Ar for one minute, then stirred at 100°C for 14 hrs. The reaction mixture was cooled to 0°C, its pH was adjusted to 5 using 6N HC1, and diluted with EtOAc. The organic layer was isolated, dried over MgS04, and concentrated under vacuum. The residue was subjected to silica gel flash chromatography using dichloromethane/methanol as the eluent to give 2-(2- aminopyridin-4-yl)-4-chlorophenol as a yellowish solid (1.8 g, yield 82%). LC/MS: m/z= 221 [M+H]+, {m/z + H) 221.
82% With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,2-dimethoxyethane; ethanol; water at 100℃; for 14h; Inert atmosphere; 22.47 2-(2-aminopyridin-4-yl)-4-chlorophenol: A mixture of 4-chloro-2-aminopyridine (1.28 g, 10 mmol), boronic acid (1.72 g, 10 mmol), Na2CO3 (3.18g, 30mmol) and Pd(PPh3)2Cl2 in DME/EtOH/H2O (4mL/2mL/4mL) was purged with Ar for one minute, then stirred at 100°C for 14 hrs. The reaction mixture was cooled to 0°C, its pH was adjusted to 5 using 6N HCl, and diluted with EtOAc. The organic layer was isolated, dried over MgSO4, and concentrated under vacuum. The residue was subjected to silica gel flash chromatography using dichloromethane/methanol as the eluent to give 2-(2-aminopyridin-4-yl)-4-chlorophenol as a yellowish solid (1.8 g, yield 82%). LC/MS: m/z= 221 [M+H]+, (m/z + H) 221.
With sodium carbonate In 1,4-dioxane; water at 90℃; for 4h; Inert atmosphere; 13 A suspension of 2-amino-4-chloropyhdine (13 g, 101 mmol), (5-chloro-2- hydroxy)benzeneboronic acid (20.9 g, 121 mmol), tetrakis triphenylphosphine palladium ( 1 1 .7 g, 10.1 mmol) and sodium carbonate (42.9 g, 404 mmol) in water (120 mL) and 1 ,4-dioxane (360 mL) was heated to 90 °C under nitrogen for 24 hours. The reaction mixture was cooled, concentrated in vacuo and the residue extracted into ethyl acetate (500 mL) before filtration. The filtrate was washed with 2N aqueous hydrogen chloride solution (500 mL) and water (700 mL). The combined aqueous layer was basified with saturated aqueous sodium bicarbonate solution (1500 mL) before extracting with ethyl acetate (2 x 800 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (2% to 12% methanol in dichloromethane gradient elution) to afford the title compound as a yellow solid (1 1 .13 g).1HNMR (400 MHz, d6-DMSO): δ 5.80 (br s, 2H), 6.60 (m, 2H), 6.95 (m, 1 H), 7.20 (m, 1 H), 7.90 (m, 1 H), 9.95 (m, 1 H).LCMS Rt = 1 .58 min MS m/z 221 [MH]+
  • 17
  • [ 89488-25-5 ]
  • [ 1354819-18-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 4 h / 90 °C / Inert atmosphere 2: potassium carbonate / dimethyl sulfoxide / 19 h / 50 °C
  • 18
  • [ 89488-25-5 ]
  • [ 1235407-36-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,2-dimethoxyethane; water / 4 h / 85 °C / Inert atmosphere 2: triethylamine / isopropyl alcohol / 18 h / 20 °C
  • 19
  • [ 89488-25-5 ]
  • 4-[2-(2-aminopyridin-4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-(5-fluoropyrimidin-2-yl)benzenesulfonamide dihydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 4 h / 90 °C / Inert atmosphere 2: potassium carbonate / dimethyl sulfoxide / 19 h / 50 °C 3: hydrogenchloride / water; methanol / 6 h / 60 °C
  • 20
  • [ 89488-25-5 ]
  • [ 1354819-10-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 4 h / 90 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 4 h / 65 °C
  • 21
  • [ 89488-25-5 ]
  • [ 1354818-89-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 4 h / 90 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 4 h / 65 °C 3: dichloromethane / 1 h / 20 °C
  • 22
  • [ 89488-25-5 ]
  • [ 1354819-12-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 4 h / 90 °C / Inert atmosphere 2: potassium carbonate / dimethyl sulfoxide / 24 h / 20 °C
  • 23
  • [ 89488-25-5 ]
  • [ 1354818-90-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 4 h / 90 °C / Inert atmosphere 2: potassium carbonate / dimethyl sulfoxide / 24 h / 20 °C 3: hydrogenchloride / 1,4-dioxane; methanol / 3 h / 65 °C
  • 24
  • [ 89488-25-5 ]
  • [ 1354819-01-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,2-dimethoxyethane; water / 4 h / 85 °C / Inert atmosphere 2.1: triethylamine / isopropyl alcohol / 18 h / 20 °C 3.1: potassium carbonate / dimethyl sulfoxide / 18 h / 20 °C 3.2: 2 h
  • 25
  • [ 89488-25-5 ]
  • [ 1354818-76-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,2-dimethoxyethane; water / 4 h / 85 °C / Inert atmosphere 2.1: triethylamine / isopropyl alcohol / 18 h / 20 °C 3.1: potassium carbonate / dimethyl sulfoxide / 18 h / 20 °C 3.2: 2 h
  • 26
  • [ 89488-25-5 ]
  • [ 1354818-78-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,2-dimethoxyethane; water / 4 h / 85 °C / Inert atmosphere 2.1: triethylamine / isopropyl alcohol / 18 h / 20 °C 3.1: potassium carbonate / dimethyl sulfoxide / 18 h / 20 °C 3.2: 2 h
  • 27
  • [ 45644-21-1 ]
  • [ 89488-25-5 ]
  • [ 1432912-46-3 ]
YieldReaction ConditionsOperation in experiment
56% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 85℃; for 16h; To a stirred mixture of <strong>[45644-21-1]2-amino-6-chloropyridine</strong> (0.26 g, 2.0 mmol ), (5-chloro- 2-hydroxy)benzene boronic acid (0.35 g, 2.0 mmol) and 2 M aqueous sodium carbonate (3 mL, 6 mmol) in p-dioxane (6 ml_) was added iefra/ /s(triphenylphosphine)palladium(0) (0.10 g, 0.086 mmol). The mixture was heated at 85 C for 16 h, allowed to cool to ambient temperature and diluted with ethyl acetate (50 mL) and water (20 mL). The organic layer was separated, washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography eluting with a gradient of 25-50% ethyl acetate in hexanes to afford 2-(6-aminopyridin-2-yl)-4-chlorophenol as a yellow solid in 56% yield (0.25 g): 1H NMR (300 MHz, CDCI3) £7.67 (d, J = 2.4 Hz, 1 H), 7.57 (dd, J = 7.8, 7.8 Hz, 1 H), 7.22-7.13 (m, 2H), 6.89 (d, J = 8.7 Hz, 1 H), 6.46 (d, J = 8.4 Hz, 1 H), 4.53 (s, 2H).
  • 28
  • [ 89488-25-5 ]
  • C30H22ClF2N5O5S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium carbonate; tetrakis(triphenylphosphine) palladium(0) / water; 1,4-dioxane / 16 h / 85 °C 2: potassium carbonate / dimethyl sulfoxide / 16 h / 20 °C 3: sodium hydrogencarbonate / water; ethanol / 16 h / Reflux
Multi-step reaction with 3 steps 1: sodium carbonate; tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 16 h / Reflux 2: potassium carbonate / dimethyl sulfoxide / 16 h / 20 °C 3: sodium hydrogencarbonate / water; ethanol / 16 h / Reflux
  • 29
  • [ 89488-25-5 ]
  • [ 1432912-68-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium carbonate; tetrakis(triphenylphosphine) palladium(0) / water; 1,4-dioxane / 16 h / 85 °C 2: potassium carbonate / dimethyl sulfoxide / 16 h / 20 °C
Multi-step reaction with 2 steps 1: sodium carbonate; tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 16 h / Reflux 2: potassium carbonate / dimethyl sulfoxide / 16 h / 20 °C
  • 30
  • [ 89488-25-5 ]
  • [ 1432912-85-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: sodium carbonate; tetrakis(triphenylphosphine) palladium(0) / water; 1,4-dioxane / 16 h / 85 °C 2: potassium carbonate / dimethyl sulfoxide / 16 h / 20 °C 3: sodium hydrogencarbonate / water; ethanol / 16 h / Reflux 4: trifluoroacetic acid / dichloromethane / 5 h / 20 °C
Multi-step reaction with 4 steps 1: sodium carbonate; tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 16 h / Reflux 2: potassium carbonate / dimethyl sulfoxide / 16 h / 20 °C 3: sodium hydrogencarbonate / water; ethanol / 16 h / Reflux 4: trifluoroacetic acid / dichloromethane / 5 h / 20 °C / Reflux
  • 31
  • [ 849200-65-3 ]
  • [ 89488-25-5 ]
  • [ 1432912-52-1 ]
YieldReaction ConditionsOperation in experiment
66% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane; water at 120℃; for 20h; 4 EXAMPLE 4 Synthesis of 5-(5-chloro-2-hydroxyphenyl)-7-(4-methoxybenzyl)imidazo[1 ,5-a]pyrazin- 8(7H)-one To a mixture of 5-bromo-7-(4-methoxybenzyl)imidazo[1 ,5-a]pyrazin-8(7 V)-one (0.167 g, 0.5 mmol (prepared according to Mukaiyama, H. er a/., Bioorg. Med. Chem. 2007, 15, 868-885)), fefra/c/'s(triphenylphosphine)palladium (0.06 g, 0.05 mmol) and (5- chloro-2-hydroxyphenyl)boronic acid in dioxane (3 mL) was added 2 M aqueous sodium carbonate (0.75 mL, 1.5 mmol). The reaction mixture was heated at 120 °C for 20 h and was allowed to cool to ambient temperature. The mixture was diluted with ethyl acetate (20 mL), filtered through a pad of sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography eluting with a 0-100% gradient of ethyl acetate in hexanes to afford 5-(5-chloro-2-hydroxyphenyl)-7-(4- methoxybenzyl)imidazo[1 ,5-a]pyrazin-8(7H)-one as an off-white solid in 66% yield (0.126 g): 1H NMR (300 MHz, acetone-cfe) £9.26 (br s, 1 H), 7.78 (s, 1 H), 7.70 (s, 1 H), 7.39 (m, 4H), 7.05 (dd, J = 7.7, 1.5 Hz, 1 H), 6.92 (s, 1 H), 6.87 (d, J = 8.6 Hz, 2H), 5.05 (s, 2H), 3.74 (s, 3H); MS (ES+) m/z 382.0 (M + 1), 383.9 (M + 1).
  • 32
  • [ 89488-25-5 ]
  • [ 120-73-0 ]
  • [ 1432912-63-4 ]
YieldReaction ConditionsOperation in experiment
20% With N,N,N,N,-tetramethylethylenediamine; copper diacetate; In methanol; water; at 20℃; for 2h; To a mixture of <strong>[120-73-0]purine</strong> (0.24 g, 2.0 mmol), copper(ll) acetate (0.36 g, 2.0 mmol) and A/,A/,A^AMetramethylethylenediamine (0.6 mL, 4 mmol) in a mixture of methanol (160 mL) and water (40 mL) was added (5-chloro-2-hydroxyphenyl)boronic acid (0.69 g, 4.0 mmol). The reaction mixture was stirred vigorously open to the atmosphere at ambient temperature for 2 h. The mixture was filtered over a pad of diatomaceous earth and the pad was washed with a mixture of dichloromethane (50 mL) and methanol (50 mL). The filtrate was concentrated in vacuo. The residue was purified by column chromatography eluting with a 0-10% gradient of methanol in dichloromethane, followed by trituration in a mixture of ethyl acetate and hexanes, to afford 4-chloro-2-(9H-purin-9-yl)phenol as a tan solid in 20% yield (0.098 g): 1H NMR (300 MHz, DMSO-de) delta 10.65 (s, 1 H), 9.26 (s, 1 H), 8.95 (s, 1 H), 8.76 (s, 1H), 7.73-7.67 (m, 1 H), 7.49-7.41 (m, 1 H), 7.17-7.09 (m, 1 H); MS (ES+) m/z 247.0 (M + 1), 248.9 (M + 1).
  • 33
  • [ 897955-34-9 ]
  • [ 89488-25-5 ]
  • [ 1432912-65-6 ]
YieldReaction ConditionsOperation in experiment
63% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water for 5h; Reflux; 12.B B. To a solution of di-terf-butyl (5-bromo-1 ,2-benzoxazol-3- yl)imidodicarbonate (3.9 g, 9.3 mmol) in dimethoxyethane (100 mL) was added (5- chloro-2-hydroxyphenyl)boronic acid (1.6 g, 9.3 mmol), tefra c/s(triphenylphosphine)palladium (1.1 g, 0.9 mmol) and 2 M aqueous sodium carbonate (9.3 mL, 18.6 mmol). The mixture was heated at reflux for 5 h, allowed to cool to ambient temperature and concentrated in vacuo. The residue was diluted with ethyl acetate (75 mL), washed with water (2 x 40 mL), dried over anhydrous sodium sulfate, filtered and concentrated/n vacuo. The residue was purified by column chromatography eluting with a 10-50% gradient of ethyl acetate in hexanes to afford di- fe/f-butyl [5-(5-chloro-2-hydroxyphenyl)-1 ,2-benzoxazol-3-yl]imidodicarbonate as a colorless solid in 63% yield (2.69 g): 1H NMR (300 MHz, DMSO-d6) £7.66 (m, 2H), 7.47-7.45 (s, 1 H), 7.22-7.19 (m, 3H), 6.90-6.87 (m, 1 H), 1.41 (s, 18H); MS (ES+) m/z 460.9 (M + 1), 462.9 (M + 1).
63% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water for 5h; Reflux;
  • 34
  • [ 1093307-36-8 ]
  • [ 89488-25-5 ]
  • [ 1432912-66-7 ]
YieldReaction ConditionsOperation in experiment
84% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water for 5h; Reflux; 13.B B. To a solution of terf-butyl 3-[bis(ieri-butoxycarbonyl)amino]-5-bromo-1 H- indazole-1 -carboxylate (2.97 g, 5.81 mmol) in dimethoxyethane (25 mL) was added (5- chloro-2-hydroxyphenyl)boronic acid (1.00 g, 5.81 mmol), tefra f s(triphenylphosphine)palladium (0.67 g, 0.58 mmol) and 2 M aqueous sodium carbonate (5.8 mL, 11.6 mmol). The mixture was heated at refluxed for 5 h, allowed to cool to ambient temperature and concentrated in vacuo. The residue was diluted with ethyl acetate (50 mL), washed with water (2 x 20 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with a 30-60% gradient of ethyl acetate in hexanes to afford ferf-butyl 3-[bis(tert-butoxycarbonyl)amino]-5-(5-chloro-2-hydroxyphenyl)-1H-indazole- 1-carboxylate as a colorless solid in 84% yield (2.57 g): H NMR (300 MHz, DMSO-d6) £8.21 (d, J = 7.8 Hz, 1 H), 7.62-7.59 (m, 2H), 7.46 (s, 1 H), 6.90-6.86 (m, 2H), 5.33 (br s, 1H), 1.72 (s, 9H), 1.42 (s, 18H); MS (ES+) mlz 560.0 (M + 1), 562.0 (M + 1).
80% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water at 120℃; for 16h;
  • 35
  • [ 1220039-64-4 ]
  • [ 89488-25-5 ]
  • [ 1354786-58-5 ]
YieldReaction ConditionsOperation in experiment
74% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In ethanol; toluene at 110℃; for 3h; Inert atmosphere; 24 Preparation 24 2-pyridazin-4-yl-4-chlorophenol To a degassed solution of (5-chloro-2-hydroxyphenyl)boronic acid (254 mg, 1 .47 mmol) in toluene (4 mL) and EtOH (0.5 mL), was added 4-bromopyridazine hydrobromide (WO2010079443, 354 mg, 1 .47 mmol) and tetrakis(triphenylphospine) palladium (86 mg, 0.074 mmol). A degassed 2M aqueous solution of Na2CO3 (624 mg, 5.89 mmol, 2.94 mL) was then added. The reaction mixture was heated to 1 10 °C under nitrogen for 3 hours. The reaction was cooled, filtered through celite, washing with EtOAc. The filtrate was concentrated in vacuo to a afford a solid, which was slurried in EtOAc, filtered, washed with EtOAc and dried to afford the title compound as a white solid (225 mg, 74%). 1H NMR (500MHz, MeOD): δ ppm 6.97 (d, 1 H), 7.35 - 7.28 (m, 1 H), 7.52 (d, 1 H), 7.98 (dd, 1 H), 9.18 (dd, 1 H), 9.52 - 9.47 (m, 1 H).
  • 36
  • [ 1432504-89-6 ]
  • [ 89488-25-5 ]
  • [ 1445881-70-8 ]
YieldReaction ConditionsOperation in experiment
68% With tetrakis(triphenylphosphine) palladium(0); copper(I) thiophene-2-carboxylate In 1,4-dioxane for 16h; Inert atmosphere; Reflux;
  • 37
  • [ 1432505-00-4 ]
  • [ 89488-25-5 ]
  • [ 21523-51-3 ]
YieldReaction ConditionsOperation in experiment
65% With tetrakis(triphenylphosphine) palladium(0); copper(I) thiophene-2-carboxylate In 1,4-dioxane for 16h; Inert atmosphere; Reflux;
  • 38
  • [ 76-09-5 ]
  • [ 89488-25-5 ]
  • [ 779331-28-1 ]
YieldReaction ConditionsOperation in experiment
2.06 g In diethyl ether at 20℃; Inert atmosphere;
In diethyl ether at 20℃; for 18h; Inert atmosphere; Sealed tube; Aryl Boronic Acid Pinacol Esters; General Procedure General procedure: A non-flame-dried round-bottom flask was charged with boronic acid, pinacol (2 equiv), and Et2O (0.1 M) and the mixture allowed to stir at r.t. for 18 h. The solvent was removed in vacuo and the crude was filtered through a plug of silica eluting with Et2O.
  • 39
  • [ 89694-48-4 ]
  • [ 89488-25-5 ]
YieldReaction ConditionsOperation in experiment
97% With boron tribromide; In dichloromethane; at 5 - 20℃; for 1h; A solution of 5-chloro-2-methoxyphenylboronic acid (10. Og, 53.6 mmol) in dichloromethan (100ml) was cooled to temperature between 5-10 C. To the above mixture, 100ml 1M solution of borontribromide in DCM was added drop wise using a pressure equalizing dropping funnel, over a period of 30 minutes. The resulting reaction mixture was then stirred room temperature for 30 minutes. After completion of reaction, the mixture was poured drop wise on to an ice cold saturated sodium bicarbonate solution (600ml). The resulting mixture was allowed to stir at room temperature for 1 hr. The DCM layer was separated out and the aqueous layer thus collected was cooled to temperature between 10-15 C. IN solution of dilute hydrochloric acid was then added to the above cooled aqueous layer and this resulted in precipitate formation. The solid was filtered off under vacuo and dried to afford 9 g (yield: 97%) of product. LC-MS: m/z = 170.9 (M+H).
97% With boron tribromide; In dichloromethane; at 5 - 20℃; for 1h; [00341] Step 1 : Preparation of (5-chloro-2-hvdroxyphenyl)boronic acid. [00342] A solution of 5-chloro-2-methoxyphenylboronic acid (10. Og, 53.6 mmol) in dichloromethan (100ml) was cooled to temperature between 5-10 C. To the above mixture, 100ml 1M solution of borontribromide in DCM was added drop wise using a pressure equalizing dropping funnel, over a period of 30 minutes. The resulting reaction mixture was then stirred at room temperature for 30 minutes. After completion of reaction, the mixture was poured drop wise on to an ice cold saturated sodium bicarbonate solution (600ml). The resulting mixture was allowed to stir at room temperature for 1 hr. The DCM layer was separated out and the aqueous layer thus collected was cooled to temperature between 10-15 C. IN solution of dilute hydrochloric acid was then added to the above cooled aqueous layer and this resulted in precipitate formation. The solid was filtered off under vacuo and dried to afford 9 g (yield: 97%) of product. LC-MS: m/z = 170.9 (M+H).
97% With boron tribromide; In dichloromethane; at 5 - 20℃; for 1h; A solution of 5-chloro-2-methoxyphenylboronic acid (10.0 g, 53.6 mmol) in dichloromethan (100 ml) was cooled to temperature between 5-10C. To the above mixture, 100 ml 1 M solution of borontribromide in DCM was added drop wise using a pressure equalizing dropping thnnel, over a period of3O minutes. The resulting reaction mixture was then stirred at room temperature for 30 minutes. After completion of reaction, the mixture was poured drop wise on to an ice cold saturated sodium bicarbonate solution (600 ml). The resulting mixture was allowed to stir at room temperature for 1 hr. The DCM layer was separated out and the aqueous layer thus collected was cooled to temperature between 10-15 C. iN solution of dilute hydrochloric acid was then added to the above cooled aqueous layer and this resulted in precipitate formation. The solid was filtered off under vacuo and dried to afford 9 g (yield: 97%) of product. LC-MS: mlz=170.9 (M+H).
  • 40
  • [ 89488-25-5 ]
  • [ 106-48-9 ]
YieldReaction ConditionsOperation in experiment
95% In dimethyl sulfoxide at 120℃; for 18h;
  • 41
  • [ 1567216-39-0 ]
  • [ 89488-25-5 ]
  • [ 1567216-51-6 ]
YieldReaction ConditionsOperation in experiment
74% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 90℃; for 3h; Microwave irradiation; 103 (S,E)-methyl 2-(7-(4-(buta-1,3-dien-1-yl)-4-methylpiperidin-1-yl)-2-(5‘-chloro-2‘-hydroxy-[1,1‘-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate To a microwave tube was added (S,E)-methyl 2-(2-(3-bromophenyl)-7-(4-(buta- 1,3 -dien- 1 -yl)-4-methylpiperidin- 1 -yl)-5- methylpyrazolo[ 1,5 -a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (100 mg, 0.172 mmol),(5-chloro-2-hydroxyphenyl)boronic acid (44.5 mg, 0.258 mmol), and 2.0 M aqueous K2CO3 (0.086 mL, 0.172 mmol) in dioxane (2 mL) and water (0.5 mL). The reaction was sparged with nitrogen for 1 minutes, treated Pd(PPh3)4 (19.87 mg, 0.0 17 mmol) then sparged for 1 mm. The reaction tube was sealed and then heated at 90 °C in a microwave tube for 1 h. LCMS analysis showed 40% completion. Additional 10 mgof Pd(PPh3)4 added and heated at 90 °C for another 2 h. The reaction was concentrated, diluted with water (15 mL) and extracted wtih EtOAc. The EtOAc layer was washed with brine, then dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by biotage (0% - 40% EtOAc in hexanes) to isolate 80 mg (74%) of the product as off-white foam. ‘H NMR (500 MHz,CDC13) 8.09 (br. s., 1H), 8.06 (d, J=7.9 Hz, 1H), 7.60 (t, J=7.5 Hz, 1H), 7.50 - 7.45(m, 1H), 7.34 (d, J=2.5 Hz, 1H), 6.99 (d, J=8.7 Hz, 1H), 6.85 (s, 1H), 6.39 (dt,J=16.9, 10.2 Hz, 1H), 6.17 (dd, J=15.4, 10.4 Hz, 1H), 6.07 (s, 1H), 5.88 (d, J=15.3Hz, 1H), 5.33 (br. s., 1H), 5.19 (d, J=17.2 Hz, 1H), 5.04 (d, J9.6 Hz, 1H), 4.50-2.50(m, 4 H), 3.75 (s, 3H), 2.64 (s, 3H), 1.93 (d, J=12.9 Hz, 1H), 1.87 - 1.73 (m, 2H),1.67 (br. s., 1H), 1.29 - 1.24 (m, 12H). LCMS (M+1) = 629.08.
  • 42
  • [ 4408-64-4 ]
  • [ 89488-25-5 ]
  • [ 1613586-37-0 ]
YieldReaction ConditionsOperation in experiment
96% In N,N-dimethyl-formamide at 120℃; for 3h; Inert atmosphere; Molecular sieve;
  • 43
  • [ 89488-25-5 ]
  • 4-(5-chloro-2-hydroxyphenyl)picolinic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / isopropyl alcohol; toluene / 20 h / 100 °C / Inert atmosphere 2: water; potassium hydroxide / tetrahydrofuran / 5 h / 100 °C
Multi-step reaction with 2 steps 1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / isopropyl alcohol; toluene / 20 h / 100 °C / Inert atmosphere 2: potassium hydroxide; water / tetrahydrofuran / 5 h / 100 °C
Multi-step reaction with 2 steps 1: potassium carbonate / isopropyl alcohol; toluene / 20 h / 100 °C / Inert atmosphere 2: water; potassium hydroxide / tetrahydrofuran / 5 h / 100 °C
  • 44
  • [ 89488-25-5 ]
  • methyl 3-(4-(5-chloro-2-hydroxyphenyl)-picolinamido)propanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / isopropyl alcohol; toluene / 20 h / 100 °C / Inert atmosphere 2.1: water; potassium hydroxide / tetrahydrofuran / 5 h / 100 °C 3.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / tetrahydrofuran / 0.5 h / 0 °C 3.2: 20 h / 0 - 20 °C
Multi-step reaction with 3 steps 1.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / isopropyl alcohol; toluene / 20 h / 100 °C / Inert atmosphere 2.1: potassium hydroxide; water / tetrahydrofuran / 5 h / 100 °C 3.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / tetrahydrofuran / 0.5 h / 0 °C 3.2: 20 h / 0 - 20 °C
Multi-step reaction with 3 steps 1.1: potassium carbonate / isopropyl alcohol; toluene / 20 h / 100 °C / Inert atmosphere 2.1: water; potassium hydroxide / tetrahydrofuran / 5 h / 100 °C 3.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran / 0.5 h / 0 °C 3.2: 20 h / 0 - 20 °C
  • 45
  • [ 89488-25-5 ]
  • methyl 3-(4-(5-chloro-2-(2-chloro-4-(N-(2,4-dimethoxybenzyl)-Ν-(1,2,4-thiadiazol-5-yl)sulfamoyl)-5-fluorophenoxy)phenyl)picolinamido)propanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / isopropyl alcohol; toluene / 20 h / 100 °C / Inert atmosphere 2.1: water; potassium hydroxide / tetrahydrofuran / 5 h / 100 °C 3.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / tetrahydrofuran / 0.5 h / 0 °C 3.2: 20 h / 0 - 20 °C 4.1: potassium carbonate / N,N-dimethyl-formamide / 3 h / 20 °C / Inert atmosphere
Multi-step reaction with 4 steps 1.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / isopropyl alcohol; toluene / 20 h / 100 °C / Inert atmosphere 2.1: potassium hydroxide; water / tetrahydrofuran / 5 h / 100 °C 3.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / tetrahydrofuran / 0.5 h / 0 °C 3.2: 20 h / 0 - 20 °C 4.1: potassium carbonate / N,N-dimethyl-formamide / 0.25 h / 20 °C / Inert atmosphere 4.2: 3 h / 20 °C / Inert atmosphere
Multi-step reaction with 4 steps 1.1: potassium carbonate / isopropyl alcohol; toluene / 20 h / 100 °C / Inert atmosphere 2.1: water; potassium hydroxide / tetrahydrofuran / 5 h / 100 °C 3.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran / 0.5 h / 0 °C 3.2: 20 h / 0 - 20 °C 4.1: potassium carbonate / N,N-dimethyl-formamide / 0.25 h / 20 °C / Inert atmosphere 4.2: 3 h / 20 °C
  • 46
  • [ 89488-25-5 ]
  • 3-(4-(5-chloro-2-(2-chloro-4-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-5-fluorophenoxy)phenyl)picolinamido)propanoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / isopropyl alcohol; toluene / 20 h / 100 °C / Inert atmosphere 2.1: water; potassium hydroxide / tetrahydrofuran / 5 h / 100 °C 3.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / tetrahydrofuran / 0.5 h / 0 °C 3.2: 20 h / 0 - 20 °C 4.1: potassium carbonate / N,N-dimethyl-formamide / 3 h / 20 °C / Inert atmosphere 5.1: water; lithium hydroxide monohydrate / tetrahydrofuran / 3 h / 20 °C
Multi-step reaction with 5 steps 1.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / isopropyl alcohol; toluene / 20 h / 100 °C / Inert atmosphere 2.1: potassium hydroxide; water / tetrahydrofuran / 5 h / 100 °C 3.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / tetrahydrofuran / 0.5 h / 0 °C 3.2: 20 h / 0 - 20 °C 4.1: potassium carbonate / N,N-dimethyl-formamide / 0.25 h / 20 °C / Inert atmosphere 4.2: 3 h / 20 °C / Inert atmosphere 5.1: water; lithium hydroxide monohydrate / tetrahydrofuran / 3 h / 20 °C
  • 47
  • [ 89488-25-5 ]
  • 3-(4-(2-(4-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2-chloro-5-fluorophenoxy)-5-chlorophenyl)picolinamido)propanoic acid hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / isopropyl alcohol; toluene / 20 h / 100 °C / Inert atmosphere 2.1: water; potassium hydroxide / tetrahydrofuran / 5 h / 100 °C 3.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / tetrahydrofuran / 0.5 h / 0 °C 3.2: 20 h / 0 - 20 °C 4.1: potassium carbonate / N,N-dimethyl-formamide / 3 h / 20 °C / Inert atmosphere 5.1: water; lithium hydroxide monohydrate / tetrahydrofuran / 3 h / 20 °C 6.1: hydrogenchloride / dichloromethane; ethyl acetate / 2 h / 20 °C
Multi-step reaction with 6 steps 1.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / isopropyl alcohol; toluene / 20 h / 100 °C / Inert atmosphere 2.1: potassium hydroxide; water / tetrahydrofuran / 5 h / 100 °C 3.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / tetrahydrofuran / 0.5 h / 0 °C 3.2: 20 h / 0 - 20 °C 4.1: potassium carbonate / N,N-dimethyl-formamide / 0.25 h / 20 °C / Inert atmosphere 4.2: 3 h / 20 °C / Inert atmosphere 5.1: water; lithium hydroxide monohydrate / tetrahydrofuran / 3 h / 20 °C 6.1: hydrogenchloride / dichloromethane; ethyl acetate / 2 h / 20 °C
Multi-step reaction with 6 steps 1.1: potassium carbonate / isopropyl alcohol; toluene / 20 h / 100 °C / Inert atmosphere 2.1: water; potassium hydroxide / tetrahydrofuran / 5 h / 100 °C 3.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran / 0.5 h / 0 °C 3.2: 20 h / 0 - 20 °C 4.1: potassium carbonate / N,N-dimethyl-formamide / 0.25 h / 20 °C / Inert atmosphere 4.2: 3 h / 20 °C 5.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 3 h / 20 °C 6.1: hydrogenchloride / dichloromethane; ethyl acetate / 2 h / 20 °C
  • 48
  • [ 19235-89-3 ]
  • [ 89488-25-5 ]
  • 4-(5-chloro-2-hydroxyphenyl)picolinonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In isopropyl alcohol; toluene at 100℃; for 20h; Inert atmosphere; 1.2 Preparation of 4-(5-chloro-2-hydroxyphenyl)picolinonitrile To a solution of 4-Chloropicolinonitrile (l .Og, 7.2 mmol) in IPA:toluene(7ml:7ml) were sequentially added (5-chloro-2-hydroxyphenyl)boronic acid (1.49g, 8.65 mmol) and potassium carbonate (3.99g, 21.64 mmol) at room temperature. The resulting reaction mixture was degassed for 15 minutes by purging with nitrogen. Thereafter calculated quantity of Tetrakis (0.416g, 0.36 mmol) was added to the reaction mixture, nitrogen purging was further continued for next 20 minutes. The resulting reaction mixture was then refluxed at 100 C for 20 hours. After completion of the reaction, the mixture was concentrated under vacuo. To the resulting crude mass water (50ml) was added and the mixture was extracted with ethyl acetate (3 x 25ml). The combined organic extract was washed with water (20ml), brine (20ml), dried over sodium sulfate and concentrated under vacuo to get the desired crude product. The crude product was purified by column chromatography using normal phase silica gel. The desired product eluted at around 20-30% ethyl acetate in hexane. Evaporation of the product fractions gave 0.8g (yield, 48%) of desired product as a solid. LC-MS: m/z = 231.1 (M+H).
48% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In isopropyl alcohol; toluene at 100℃; for 20h; Inert atmosphere; 1.2 Step 2: Preparation of 4-(5-chloro-2-hydroxyphenyl)picolinonitrile [00343] Step 2: Preparation of 4-(5-chloro-2-hydroxyphenyl)picolinonitrile [00344] To a solution of 4-Chloropicolinonitrile (l .Og, 7.2 mmol) in IPA:toluene(7ml:7ml) were sequentially added (5-chloro-2-hydroxyphenyl)boronic acid (1.49g, 8.65 mmol) and potassium carbonate (3.99g, 21.64 mmol) at room temperature. The resulting reaction mixture was degassed for 15 minutes by purging with nitrogen. Thereafter calculated quantity of Tetrakis (0.416g, 0.36 mmol) was added to the reaction mixture and nitrogen purging was further continued for next 20 minutes. The resulting reaction mixture was then refluxed at 100 C for 20 hours. After completion of the reaction, the mixture was concentrated under vacuo. To the resulting crude mass water (50ml) was added and the mixture was extracted with ethyl acetate (3 x 25ml). The combined organic extract was washed with water (20ml), brine (20ml), dried over sodium sulfate and concentrated under vacuo to get the desired crude product. The crude product was purified by column chromatography using normal phase silica gel. The desired product eluted at around 20-30% ethyl acetate in hexane. Evaporation of the product fractions gave 0.8g (yield, 48%) of desired product as a solid. LC-MS: m/z = 231.1 (M+H).
48% With potassium carbonate In isopropyl alcohol; toluene at 100℃; for 20h; Inert atmosphere; 1.2 Step 2: Preparation of4-(5-chloro-2-hydroxyphenyl)picolinonitrile To a solution of 4-Chloropicolinonitrile (1.0 g, 7.2 mmol) in IPA:toluene (7 ml:7 ml) were sequentially added (5-chloro-2-hydroxyphenyl)boronic acid (1.49 g, 8.65 mmol) and potassium carbonate (3.99 g, 21.64 mmol) at room temperature. The resulting reaction mixture was degassed for 15 minutes by purging with nitrogen. Thereafier calculated quantity of Tetrakis (0.416 g, 0.36 mmol) was added to the reaction mixture and nitrogen purging was further continued for next 20 minutes. The resulting reaction mixture was then refluxed at 100° C. for 20 hours. Afier completion of the reaction, the mixture was concentrated under vacuo. To the resulting crude mass water (50 ml) was added and the mixture was extracted with ethyl acetate (3x25 ml). The combined organic extract was washed with water (20 ml), brine (20 ml), dried over sodium sulfate and concentrated under vacuo to get the desired crude product. The crude product was purified by column chromatography using normal phase silica gel. The desired product eluted at around 20-30% ethyl acetate in hexane. Evaporation of the product fractions gave 0.8 g (yield, 48%) of desired product as a solid. LC-MS: mlz=23 1.1 (M+H).
  • 49
  • [ 89488-25-5 ]
  • [ 30766-03-1 ]
  • 4-(5-chloro-2-hydroxyphenyl)picolinic acid hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane; water for 18h; Inert atmosphere; Reflux; 43 Preparation 43
4-(5-chloro-2-hydroxyphenyl)picolinic acid hydrochloride Preparation 43 4-(5-chloro-2-hydroxyphenyl)picolinic acid hydrochloride A solution of (5-chloro-2-hydroxyphenyl)boronic acid (16.85 g, 97.7 mmol), 4- bromopicolinic acid (19.74 g, 97.7 mmol) and sodium carbonate (41.43 g, 39.1 mmol) in dioxane (300 mL) and water (120 mL) was degassed with nitrogen before the addition of tetrakistriphenylphosphine palladium (0) (11.3 g, 9.77 mmol) and the reaction was heated to reflux for 18 hours. The reaction was cooled and quenched by the addition of 2M NaOH (aq) until pH>10. The reaction was filtered through Celite and extracted with TBME (2 x 250 mL). The aqueous layer was acidified to pH=7 using 3M HCI (aq) and the resulting precipitate was collected by filtration. The solid was suspended in water (200 mL), treated with 2M HCI (aq) (250 mL) and stirred for 30 minutes. The precipitate was collected and dried in vacuo azeotroping with MeOH and MeCN to afford the title compound. (0831) 1 H NMR (400MHz, DMSO-d6): δ ppm 7.00 (d, 1 H), 7.30 (m, 1 H), 7.45 (m, 1 H), 7.80 (m, 1 H), 8.25 (m, 1 H), 8.70 (d, 1 H), 10.40 (br s, 1 H). (0832) MS m/z 250 [M+H]+
  • 54
  • [ 89488-25-5 ]
  • 4-(4-chloro-2-(5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3-yl)phenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide*2,2,2-trifluoroacetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium carbonate; tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 16 h / Reflux 2: potassium carbonate / dimethyl sulfoxide / 16 h / 20 °C 3: dichloromethane / 4 h / 20 °C
  • 55
  • [ 89488-25-5 ]
  • [ 1432913-70-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium carbonate; tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 16 h / Reflux 2: potassium carbonate / dimethyl sulfoxide / 16 h / 20 °C 3: trifluoroacetic acid / dichloromethane / 4 h / 20 °C
  • 56
  • [ 89488-25-5 ]
  • 4-(2-(1H-benzo[d]imidazol-5-yl)-4-chlorophenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide*2,2,2-trifluoroacetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium carbonate; tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 16 h / Reflux 2: potassium carbonate / dimethyl sulfoxide / 16 h / 20 °C 3: dichloromethane / 4 h / 20 °C
  • 57
  • [ 89488-25-5 ]
  • [ 1432913-51-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium carbonate; tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 16 h / Reflux 2: potassium carbonate / dimethyl sulfoxide / 16 h / 20 °C 3: trifluoroacetic acid / dichloromethane / 4 h / 20 °C
  • 58
  • [ 949922-61-6 ]
  • [ 89488-25-5 ]
  • [ 1432912-49-6 ]
  • 59
  • [ 50998-17-9 ]
  • [ 89488-25-5 ]
  • [ 1432913-71-7 ]
  • 60
  • [ 89488-25-5 ]
  • [ 4887-88-1 ]
  • [ 1432913-98-8 ]
  • 62
  • [ 39513-26-3 ]
  • [ 89488-25-5 ]
  • [ 1432912-78-1 ]
  • 63
  • cis-tert-butyl 2-(3-(4-bromophenyl)cyclobutoxy)acetate [ No CAS ]
  • [ 89488-25-5 ]
  • cis-tert-butyl 2-(3-(5'-chloro-2'-hydroxy-[1,1'-biphenyl]-4-yl)cyclobutoxy)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; for 8h; Inert atmosphere; 24.24A 24A. Cis-tert-butyl 2-( -(5'-chloro-2'-hydroxy-[l, -biphenyl]-4-yl)cyclobutoxy)acetate 24A. Cis-tert-butyl 2-( -(5'-chloro-2'-hydroxy-[l, -biphenyl]-4-yl)cyclobutoxy)acetate [00175] A mixture of cis-tert-butyl 2-(3-(4-bromophenyl)cyclobutoxy)acetate (60 mg, 0.18 mmol), (5-chloro-2-hydroxyphenyl)boronic acid (36 mg, 0.21 mmol), (Ph3P)4Pd (20 mg, 0.02 mmol) and K2CO3 (73 mg, 0.53 mmol) in THF (2 mL) and water (0.7 mL) was heated at 80 °C for 8 h under Ar, then was cooled to rt. The reaction was acidified with IN aq. HC1 to pH = 2~3, and extracted with EtOAc (4 x 10 mL). The combined organic extracts were dried (MgS04) and concentrated in vacuo to afford the crude product, which was chromatographed (S1O2; 12 g; eluted with EtOAc/Hexanes 0% to 30% over 20 min) to give the title compound (42 mg, 0.11 mmol, 61% yield) as a beige solid. LCMS, [M+Na]+ = 410.9. H MR (500 MHz, CDC13) δ 7.41 - 7.35 (m, 4H), 7.22 - 7.18 (m, 2H), 6.94 - 6.90 (m, 1H), 4.17 - 4.05 (m, 1H), 3.96 (s, 2H), 3.10 - 2.99 (m, 1H), 2.82 - 2.69 (m, 2H), 2.24 - 2.12 (m, 2H), 1.51 (s, 9H).
  • 64
  • 3,5-dichloro-2-vinylpyrazine [ No CAS ]
  • [ 89488-25-5 ]
  • potassium phenyltrifluoborate [ No CAS ]
  • 8-chloro-3-phenyl-10,11-dihydrobenzo[6,7]oxepino[2,3-b]pyrazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With [Rh(OH)(cod)]2; cesiumhydroxide monohydrate; palladium diacetate; tricyclohexylphosphine tetrafluoroborate In 1,4-dioxane; water at 20 - 100℃; for 18.5h; Inert atmosphere; Sealed tube; (MC)2R of Dichlorovinylpyrazine; General Procedure General procedure: A 2-dram vial was charged with aryl trifluoroborate (2 or 3 equiv), hydroxy(cyclooctadiene)rhodium(I) dimer (2 mol%), palladium(II) acetate (2.5 mol%), tricyclohexylphosphonium tetrafluoroborate (5 mol%), and cesium hydroxide monohydrate (6 equiv), then purged with argon. Another 2-dram vial was charged with compound 3 (1equiv) and boronic acid pinacol ester (2 equiv) and purged with argon. Dioxane (1 mL) was used to transfer the vinyl pyrazine and boronic acid pinacol ester to the vial with the remaining reagents, rinsing with additional dioxane (2*500 μL). Following the addition of H2O (200 μL), the vial was sealed with a Teflon cap and the contents allowed to stir at r.t. for 30 min before being heated to 100 °C for 18 h. After cooling to r.t., the mixture was passed through a silica plug (EtOAc) and concentrated in vacuo. Silica flash column chromatography (hexane/EtOAc, 9:1) gave the pure products.
  • 65
  • [ 121-43-7 ]
  • [ 826-26-6 ]
  • [ 7732-18-5 ]
  • [ 89488-25-5 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 1-chloro-4-(methoxymethoxy)benzene With n-butyllithium In tetrahydrofuran; hexane at 0 - 20℃; for 2h; Stage #2: Trimethyl borate In tetrahydrofuran; hexane at 0 - 20℃; for 1h; Stage #3: water With hydrogenchloride at 0 - 20℃; for 24h;
  • 66
  • [ 1344713-92-3 ]
  • [ 89488-25-5 ]
  • [ 401-86-5 ]
  • (S)-5-chloro-2'-(((3-hydroxy-5-(trifluoromethyl)phenyl)amino)methyl)-6'-methyl-[1,1'-biphenyl]-2-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% Stage #1: (2-formylphenyl)-6-methyl trifluoromethanesulfonate; (5‐chloro‐2‐hydroxyphenyl)boronic acid With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water for 12h; Reflux; Stage #2: 3-amino-5-(1,1,1-trilfluoromethyl)phenol With (R)-3,3'-di(anthracen-9-yl)-5,5',6,6',7,7',8,8'-octahydro-[1,1'-binaphthalene]-2,2'-diyl hydrogen phosphate; di-isopropyl 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate In toluene at 20℃; for 24h; Molecular sieve; enantioselective reaction;
  • 67
  • [ 1344713-92-3 ]
  • [ 89488-25-5 ]
  • [ 454-82-0 ]
  • (R)-5-chloro-2'-(((2-hydroxy-4-(trifluoromethyl)phenyl)amino)methyl)-6'-methyl-[1,1'-biphenyl]-2-ol [ No CAS ]
  • 68
  • [ 89488-25-5 ]
  • C21H19ClN4 [ No CAS ]
  • (S)-4-chloro-2-(3-(3-methyl-1H-indazol-5-yl)-5-(1-phenylethylamino)pyridin-2-yl)phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
52% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 120℃; for 2h; Microwave irradiation; Inert atmosphere;
  • 69
  • [ 89488-25-5 ]
  • C21H19ClN4O [ No CAS ]
  • (R)-4-chloro-2-(5-(2-hydroxy-2-phenylethylamino)-3-(3-methyl-1H-indazol-5-yl)pyridin-2-yl)phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
44% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 120℃; for 2h; Microwave irradiation; Inert atmosphere;
  • 70
  • [ 89488-25-5 ]
  • (R)-2-(6-chloro-5-(3-methyl-1H-indazol-5-yl)pyridin-3-ylamino)-2-phenylethanol [ No CAS ]
  • (R)-4-chloro-2-[5-(2-hydroxy-1-phenylethylamino)-3-(3-methyl-1H-indazol-5-yl)pyridin-2-yl]phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
47% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 120℃; for 2h; Microwave irradiation; Inert atmosphere;
  • 71
  • [ 89488-25-5 ]
  • (R)-2-(6-chloro-5-(3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ylamino)-2-phenylethanol [ No CAS ]
  • (R)-4-chloro-2-(5-(2-hydroxy-1-phenylethylamino)-3-(3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-2-yl)phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 120℃; for 2h; Microwave irradiation; Inert atmosphere;
  • 72
  • [ 89488-25-5 ]
  • (R)-2-(6-chloro-5-(isoquinolin-6-yl)pyridin-3-ylamino)-2-phenylethanol [ No CAS ]
  • (R)-4-chloro-2-(5-(2-hydroxy-1-phenylethylamino)-3-(isoquinolin-6-yl)pyridin-2-yl)phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 120℃; for 2h; Microwave irradiation; Inert atmosphere;
  • 73
  • [ 89488-25-5 ]
  • (R)-5-(2-chloro-5-(2-hydroxy-1-phenylethylamino)pyridin-3-yl)-indolin-2-one [ No CAS ]
  • (R)-5-(2-(5-chloro-2-hydroxyphenyl)-5-(2-hydroxy-1-phenylethylamino)pyridin-3-yl)indolin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
46% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 120℃; for 2h; Microwave irradiation; Inert atmosphere;
  • 74
  • [ 89488-25-5 ]
  • (R)-N-(4-(2-chloro-5-(2-hydroxy-1-phenylethylamino)pyridin-3-yl)phenyl)acetamide [ No CAS ]
  • (R)-N-(4-(2-(5-chloro-2-hydroxyphenyl)-5-(2-hydroxy-1-phenylethylamino)pyridin-3-yl)phenyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 120℃; for 2h; Microwave irradiation; Inert atmosphere;
  • 75
  • [ 89488-25-5 ]
  • (R)-2-(6-chloro-5-(1H-indol-5-yl)pyridin-3-ylamino)-2-phenylethanol [ No CAS ]
  • (R)-4-chloro-2-(5-(2-hydroxy-1-phenylethylamino)-3-(1H-indol-5-yl)pyridin-2-yl)phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 120℃; for 2h; Microwave irradiation; Inert atmosphere;
  • 76
  • [ 89488-25-5 ]
  • (S)-2-(6-chloro-5-(3-methyl-1H-indazol-5-yl)pyridin-3-ylamino)-2-phenylethanol [ No CAS ]
  • (S)-4-chloro-2-(5-(2-hydroxy-1-phenylethylamino)-3-(3-methyl-1H-indazol-5-yl)pyridin-2-yl)phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
46% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 120℃; for 2h; Microwave irradiation; Inert atmosphere;
  • 77
  • [ 6287-82-7 ]
  • [ 89488-25-5 ]
  • 2-(3-bromobenzo(b)thiophen-2-yl)-4-chlorophenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃; for 6h;Schlenk technique; 1) accurate weighing 2, 3 - b bromophenylacetic and [b] Thiophene (300 mg, 1.0 mmol), 5 - chloro -2 - hydroxy phenyl boronic acid (300 mg, 1.6 mmol), and in turn to 25 ml of in shu Lunke bottle, adding potassium carbonate (414 mg, 3 mmol), four (triphenylphosphine) palladium (0.05 equivalent), 1, 4 - dioxane/water (volume ratio 4:1), is 90 C reaction in oil bath 6 hours. After the reaction, the solvent is removed under reduced pressure, the use of silica gel column separation, petroleum ether/ethyl acetate as eluant, to obtain 2 - (3 - bromophenylacetic and [b] Thiophene -2 - yl) -4 - chlorophenol 3j, the yield is 82%
  • 78
  • [ 32969-25-8 ]
  • [ 89488-25-5 ]
  • 2-(3-bromo-5-chlorobenzo(b)thiophen-2-yl)-4-chlorophenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 90℃; for 6h; Schlenk technique; 12.1 1) accurate weighing 2, 3 - dibromo -5 - chlorobenzene and [b] Thiophene (330 mg, 1.0 mmol), 5 - chloro -2 - hydroxy phenyl boronic acid (220 mg, 1.5 mmol), and in turn to 25 ml of in shu Lunke bottle, adding potassium carbonate (552 mg, 4.0 mmol), four (triphenylphosphine) palladium (0.05 equivalent), 1, 4 - dioxane/water (volume ratio 4:1), is 90 °C reaction in oil bath 6 hours. After the reaction, the solvent is removed under reduced pressure, the use of silica gel column separation, petroleum ether/ethyl acetate as eluant, to obtain 2 - (3 - bromo -5 - chlorobenzene and [b] Thiophene -2 - yl) -4 - chlorophenol 3l, the yield is 64%.1
64% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 90℃; Schlenk technique; Inert atmosphere; Darkness; regioselective reaction;
  • 80
  • (1R,2R)-ethyl-2-(4-bromophenethyl)cyclopropanecarboxylate [ No CAS ]
  • [ 89488-25-5 ]
  • trans-ethyl 2-(2-(5’-chloro-2’-hydroxy-[1,1’-biphenyl]-4-yl)ethyl)cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; for 0.333333h; Microwave irradiation; Inert atmosphere; 26E 26E. Trans-ethyl 2-(2-(5′-chloro-2′-hydroxy-[1,1′-biphenyl]-4-yl)ethyl) cyclopropanecarboxylate (Enantiomer 1; absolute stereochemistry shown is arbitrary) A mixture of 26D (70 mg, 0.236 mmol), (5-chloro-2-hydroxyphenyl)boronic acid (49 mg, 0.283 mmol), Pd(PPh3)4(27 mg, 0.024 mmol) and K2CO3 (98 mg, 0.707 mmol) in THF (3 mL) and water (1 mL) was heated in a microwave reactor at 80° C. for 20 min. under Ar, then was cooled to rt. The reaction was acidified with 1N aq. HCl to pH=2-3, and extracted with EtOAc (4×20 mL). The combined organic extracts were dried over MgSO4, and concentrated in vacuo. The residue was chromatographed (SiO2; 12 g; gradient of EtOAc/Hexane from 0% to 20% over 20 min) to give the title compound (60 mg, 0.174 mmol, 74% yield) as a colorless oil. LCMS, [M-H]+=343.2.
  • 81
  • [ 89488-25-5 ]
  • [ 30766-03-1 ]
  • 4-(5-chloro-2-hydroxyphenyl)picolinic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% With sodium carbonate In 1,4-dioxane; water at 87 - 88℃; for 29h; Inert atmosphere; 4-(5-Chloro-2-hydroxyphenyl)picolinic acid A mixture of 5-chloro-2-hydroxyphenylboronic acid (20) (171.5 g, 995 mmol), 4-bromopicolinic acid (201.5 g, 998 mmol), sodium carbonate (424 g, 4.0 Mole), dioxane (3 L) and water (1 L) was de-gassed with 5 x vac/N2 cycles. Palladium acetate (7.5 g, 33.4 mmol) and triphenylphosphine (27.5 g, 105 mmol) were added and the mixture was de-gassed again with 2 x vac/N2 cycles. The mixture was heated to 87-88 °C (reflux) for 29 hours then cooled to room temperature overnight. 4M NaOH (250 mL, 1 mole) was added and the mixture filtered through a plug of celite, washing with 1M NaOH (1.5 L). The filtrate was diluted with water (1 L) and extracted with MTBE (2 L then 2 x 1 L). The organic layers were sequentially re-extracted with water (500 mL). The combined aqueous layers were acidified to pH 4-5 with 6M HCl (1.28 L) [added slowly to control CO2 evolution and temperature - kept 15-23 °C]. The slurry was filtered, washed with water (1 L) and dried under vacuum to afford the title compound as a beige solid 248 g. Assume 100% yield. 1H NMR (500 MHz, DMSO-d6) d 11.03 (br s, 1H), 8.54 (d, J = 4.9 Hz, 1H), 8.21 (s, 1H), 7.61 (d, J = 4.9 Hz, 1H), 7.38 (d, J = 2.4 Hz, 1H), 7.28 (dd, J = 8.8, 2.4 Hz, 1H), 7.11 (d, J = 8.8 Hz, 1H).
  • 82
  • [ 89488-25-5 ]
  • N‐(3,4‐dichlorobenzyl)‐2,2,2,‐trifluoroacetamide [ No CAS ]
  • N‐((5',6‐dichloro‐2'‐hydroxy‐[1,1'‐biphenyl]‐3‐yl)methyl)‐1,1,1‐trifluoromethanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With sodium 2'‐(dicyclohexylphosphaneyl)‐2,6‐diisopropyl‐[1,1'‐biphenyl]‐3‐sulfonate; potassium phosphate; palladium diacetate In tetrahydrofuran; water at 60℃; for 16h; Inert atmosphere;
  • 83
  • [ 89488-25-5 ]
  • (S)-4-(7-chloro-6-fluoro-1-(2-isopropyl-6-methylphenyl)-2-oxo-1,2-dihydropyrido[2,3-d]pyrimidin-4-yl)-3-methylpiperazin-1-carboxylic acid tert-butyl ester [ No CAS ]
  • (S)-tert-butyl 4-(7-(5-chloro-2-hydroxyphenyl)-6-fluoro-1-(2-isopropyl-6-methylphenyl)-2-oxo-1,2-dihydropyrido[2,3-d]pyrimidin-4-yl)-3-methylpiperazine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In 1,4-dioxane; water at 90℃; Inert atmosphere; 113.2 [0456] Step 2: (S)-tert-Butyl 4-(7-(5-chloro-2-hydroxyphenyl)-6-fluoro-1-(2-isopropyl- 6-methylphenyl)-2-oxo-1,2-dihydropyrido[2,3-d]pyrimidin-4-yl)-3-methylpiperazine-1- carboxylate. A reaction mixture of (S)-tert-butyl 4-(7-chloro-6-fluoro-1-(2-isopropyl-6- methylphenyl)-2-oxo-1,2-dihydropyrido[2,3-d]pyrimidin-4-yl)-3-methylpiperazine-1- carboxylate (Intermediate 113A, 400 mg, 0.76 mmol), 5-chloro-2-hydroxyphenylboronic acid (195 mg, 1.13 mmol, CombiPhos Catalyst, Trenton, NJ), Pd(dppf)Cl2 (62 mg, 0.075 mmol), potassium acetate (370 mg, 3.8 mmol) in 1,4-dioxane (3.7 mL), and water (0.1 mL) was purged with nitrogen for 10 min. The reaction mixture was heated 90 °C for 90 min, and was then partitioned between water (50 mL) and EtOAc (50 mL). The aqueous phase was extracted with EtOAc. The combined organic layers were dried over MgSO4 and concentrated in vacuo to give (S)-tert-butyl 4-(7-(5-chloro-2-hydroxyphenyl)-6-fluoro-1-(2-isopropyl-6- methylphenyl)-2-oxo-1,2-dihydropyrido[2,3-d]pyrimidin-4-yl)-3-methylpiperazine-1- carboxylate which was used without further purification in the following step. m/z (ESI, +ve ion): 622.2 (M+H)+.
  • 84
  • [ 5471-63-6 ]
  • [ 89488-25-5 ]
  • 2-chloro-9,10-diphenyl-9,10-dihydro-9,10-epoxyanthracene [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: (5‐chloro‐2‐hydroxyphenyl)boronic acid With 2,2-Dimethyl-1,3-propanediol In dichloromethane at 20℃; for 3h; Schlenk technique; Inert atmosphere; Stage #2: With toluene Inert atmosphere; Stage #3: 1,3-diphenylisobenzofuran With Nonafluorobutanesulfonyl fluoride; sodium hydride; caesium carbonate In tetrahydrofuran; paraffin oil at 60℃; for 24h; Schlenk technique; Inert atmosphere;
  • 85
  • [ 42925-43-9 ]
  • [ 89488-25-5 ]
  • C18H19ClO2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
96 % ee With C46H48Cl2O4Rh2; potassium hydroxide In ethanol; water at 60℃; for 12h; Schlenk technique; Inert atmosphere; enantioselective reaction;
Same Skeleton Products
Historical Records

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