1235865-77-6

Basic information

• Synonyms: 2-[(1H-Pyrrolo[2,3-b]pyridin-5-yl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl]methyl]piperazin-1-yl]benzoic acid;4-[4-[[2-(4-chlorophenyl)-4,4-dimethyl-1-cyclohexen-1-yl]methyl]-1-piperazinyl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzoic acid;2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid;2-((1H-pyrrolo[2,3-b] yridine-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid;4-[4-[[2-(4-chlorophenyl)-4,4-dimethyl-1-cyclohexen-1-yl]methyl]-1-piperazinyl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzoic aci;2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazin-1-yl)benzamide;Benzoic acid, 4-[4-[[2-(4-chlorophenyl)-4,4-dimethyl-1-cyclohexen-1-yl]methyl]-1-piperazinyl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)-
• CAS NO: 1235865-77-6
• Molecular Formula: C₃₃H₃₅ClN₄O₃
• Molecular Weight: 571.109
• EINECS: 1592732-453-0
• Mol File: 1235865-77-6.mol
• Article Data: 20

Chemical Properties

• Appearance: /
• Density: 1.282±0.06 g/cm3(Predicted)
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 4.05±0.36(Predicted)
• CAS DataBase Reference: N/A(CAS DataBase Reference)
• NIST Chemistry Reference: N/A(1235865-77-6)
• EPA Substance Registry System: N/A(1235865-77-6)

Safety Data

• Hazardous Substances Data: 1235865-77-6(Hazardous Substances Data)

Usage

General Description

2-((1H-Pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid is a complex organic compound with a mixture of various chemical functionalities including a pyrrolopyridine ring, benzene carboxylic acid, tetrahydrobiphenyl, a chlorine atom, and a piperazine ring. The structure suggests that this molecule could be a potential drug molecule or a biologically active compound, although without additional information, its exact uses or properties cannot be determined conclusively. Some of the functionalities like piperazine rings are often seen in drug molecules and are known for their biological activity. Similarly, benzoic acid derivatives are another common motif in medicinal chemistry due to their interesting pharmacological properties. However, the specific activities of this particular compound would need to be investigated further.

Synthetic route

2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid methyl ester (1235865-76-5) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
With sodium hydroxide In tetrahydrofuran; methanol; water at 45℃;	96.9%
With water; sodium hydroxide In tetrahydrofuran; ethanol at 20℃;	93%
With water; sodium hydroxide In dimethyl sulfoxide at 20℃; for 3h; Solvent; Reagent/catalyst; Temperature;	92%

tert-butyl 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)-oxy)-4-(4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoate → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
With potassium tert-butylate In 2-methyltetrahydrofuran; water for 2h; Inert atmosphere; Large scale;	88%
With potassium tert-butylate In 2-methyltetrahydrofuran; water at 55℃; Inert atmosphere;	85%
With potassium tert-butylate; water In 2-methyltetrahydrofuran at 50℃; for 5h; Inert atmosphere;	57.6%

C27H33ClN2O3 + 5-bromo-1H-pyrrolo[2,3-b]pyridine (183208-35-7) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Stage #1: C27H33ClN2O3; 5-bromo-1H-pyrrolo[2,3-b]pyridine With copper(l) iodide; caesium carbonate In dimethyl sulfoxide at 80℃; for 3h; Stage #2: With methanol; sodium hydroxide at 65℃; Solvent; Temperature; Reagent/catalyst;	83%

5-bromo-1H-pyrrolo[2,3-b]pyridine (183208-35-7) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.17 h 1.2: 24 h / 20 °C 2.1: n-butyllithium / tetrahydrofuran / 0.03 h / -78 °C 2.2: 1 h / -78 - 20 °C 2.3: 1 h / 0 °C 3.1: potassium phosphate / diethylene glycol dimethyl ether / 24 h / 115 °C 4.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 5.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C 5.2: Cooling View Scheme
Multi-step reaction with 5 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.17 h 1.2: 24 h / 20 °C 2.1: n-butyllithium / tetrahydrofuran / 0.03 h / -78 °C 2.2: 1 h / 20 °C 2.3: 1 h / 0 °C 3.1: potassium phosphate / diethylene glycol dimethyl ether / 24 h / 115 °C 4.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 5.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C View Scheme
Multi-step reaction with 5 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.17 h 1.2: 24 h / 20 °C 2.1: n-butyllithium / tetrahydrofuran; hexane / 0.03 h / -78 °C 2.2: 1 h / -78 - 20 °C 3.1: potassium phosphate / diethylene glycol dimethyl ether / 24 h / 115 °C 4.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 5.1: sodium hydroxide; water / 1,4-dioxane / 24 h / 50 °C View Scheme

5-bromo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (858116-66-2) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran / 0.03 h / -78 °C 1.2: 1 h / -78 - 20 °C 1.3: 1 h / 0 °C 2.1: potassium phosphate / diethylene glycol dimethyl ether / 24 h / 115 °C 3.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 4.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C 4.2: Cooling View Scheme
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran / 0.03 h / -78 °C 1.2: 1 h / 20 °C 1.3: 1 h / 0 °C 2.1: potassium phosphate / diethylene glycol dimethyl ether / 24 h / 115 °C 3.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 4.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C View Scheme
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran; hexane / 0.03 h / -78 °C 1.2: 1 h / -78 - 20 °C 2.1: potassium phosphate / diethylene glycol dimethyl ether / 24 h / 115 °C 3.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 4.1: sodium hydroxide; water / 1,4-dioxane / 24 h / 50 °C View Scheme
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran / 0.03 h / -78 °C 1.2: 1 h / -78 - 20 °C 1.3: 1 h / 0 °C 2.1: potassium phosphate / diethylene glycol dimethyl ether / 24 h / 115 °C 3.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 4.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C View Scheme
Multi-step reaction with 4 steps 1.1: n-butyllithium; Trimethyl borate / tetrahydrofuran / 1 h / -78 - 20 °C 1.2: 1 h / 0 °C 2.1: potassium phosphate / diethylene glycol dimethyl ether / 24 h / 115 °C 3.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 4.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C View Scheme

methyl 4,4-dimethyl-2-oxocyclohexancarboxylate (32767-46-7) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: sodium hydride / dichloromethane / 0.5 h / 0 °C 1.2: 24 h / -78 - 20 °C 2.1: cesium fluoride / tetrakis(triphenylphosphine) palladium(0) / 1,2-dimethoxyethane; methanol / 24 h / 70 °C 3.1: lithium borohydride; methanol / diethyl ether / 24 h / 20 °C 4.1: triethylamine; methanesulfonyl chloride / dichloromethane / 0.02 h / 0 °C 4.2: 24 h / 20 °C 5.1: trifluoroacetic acid; triethylsilane / dichloromethane / 1 h 6.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 7.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C 7.2: Cooling View Scheme
Multi-step reaction with 7 steps 1.1: sodium hydride / dichloromethane / 0.5 h / 0 °C 1.2: -78 - 20 °C 2.1: cesium fluoride / tetrakis(triphenylphosphine) palladium(0) / 1,2-dimethoxyethane; methanol / 24 h / 70 °C 3.1: lithium borohydride; methanol / diethyl ether / 24 h / 20 °C 4.1: triethylamine; methanesulfonyl chloride / dichloromethane / 0.02 h / 0 °C 4.2: 24 h / 20 °C 5.1: trifluoroacetic acid; triethylsilane / dichloromethane / 1 h 6.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 7.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C View Scheme
Multi-step reaction with 7 steps 1.1: sodium hydride / dichloromethane / 0.5 h / 0 °C 1.2: 24 h / -78 - 20 °C 2.1: tetrakis(triphenylphosphine) palladium(0); cesium fluoride / 1,2-dimethoxyethane; methanol / 24 h / 70 °C 3.1: lithium borohydride / methanol / 24 h / 20 °C 4.1: methanesulfonyl chloride; triethylamine / dichloromethane / 0.02 h / 0 °C 4.2: 24 h / 20 °C 5.1: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h 6.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 7.1: sodium hydroxide; water / 1,4-dioxane / 24 h / 50 °C View Scheme

methyl 4,4-dimethyl-2-(((trifluoromethyl)sulfonyl)oxy)cyclohex-1-ene-1-carboxylate (1228780-46-8) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: cesium fluoride / tetrakis(triphenylphosphine) palladium(0) / 1,2-dimethoxyethane; methanol / 24 h / 70 °C 2.1: lithium borohydride; methanol / diethyl ether / 24 h / 20 °C 3.1: triethylamine; methanesulfonyl chloride / dichloromethane / 0.02 h / 0 °C 3.2: 24 h / 20 °C 4.1: trifluoroacetic acid; triethylsilane / dichloromethane / 1 h 5.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 6.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C 6.2: Cooling View Scheme
Multi-step reaction with 6 steps 1.1: cesium fluoride / tetrakis(triphenylphosphine) palladium(0) / 1,2-dimethoxyethane; methanol / 24 h / 70 °C 2.1: lithium borohydride; methanol / diethyl ether / 24 h / 20 °C 3.1: triethylamine; methanesulfonyl chloride / dichloromethane / 0.02 h / 0 °C 3.2: 24 h / 20 °C 4.1: trifluoroacetic acid; triethylsilane / dichloromethane / 1 h 5.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 6.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C View Scheme
Multi-step reaction with 6 steps 1.1: tetrakis(triphenylphosphine) palladium(0); cesium fluoride / 1,2-dimethoxyethane; methanol / 24 h / 70 °C 2.1: lithium borohydride / methanol / 24 h / 20 °C 3.1: methanesulfonyl chloride; triethylamine / dichloromethane / 0.02 h / 0 °C 3.2: 24 h / 20 °C 4.1: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h 5.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 6.1: sodium hydroxide; water / 1,4-dioxane / 24 h / 50 °C View Scheme

4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carboxylic acid methyl ester (1228780-49-1) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: lithium borohydride; methanol / diethyl ether / 24 h / 20 °C 2.1: triethylamine; methanesulfonyl chloride / dichloromethane / 0.02 h / 0 °C 2.2: 24 h / 20 °C 3.1: trifluoroacetic acid; triethylsilane / dichloromethane / 1 h 4.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 5.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C 5.2: Cooling View Scheme
Multi-step reaction with 5 steps 1.1: lithium borohydride; methanol / diethyl ether / 24 h / 20 °C 2.1: triethylamine; methanesulfonyl chloride / dichloromethane / 0.02 h / 0 °C 2.2: 24 h / 20 °C 3.1: trifluoroacetic acid; triethylsilane / dichloromethane / 1 h 4.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 5.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C View Scheme
Multi-step reaction with 5 steps 1.1: lithium borohydride / methanol / 24 h / 20 °C 2.1: methanesulfonyl chloride; triethylamine / dichloromethane / 0.02 h / 0 °C 2.2: 24 h / 20 °C 3.1: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h 4.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 5.1: sodium hydroxide; water / 1,4-dioxane / 24 h / 50 °C View Scheme

(4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methanol (1228780-51-5) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: triethylamine; methanesulfonyl chloride / dichloromethane / 0.02 h / 0 °C 1.2: 24 h / 20 °C 2.1: trifluoroacetic acid; triethylsilane / dichloromethane / 1 h 3.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 4.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C 4.2: Cooling View Scheme
Multi-step reaction with 4 steps 1.1: triethylamine; methanesulfonyl chloride / dichloromethane / 0.02 h / 0 °C 1.2: 24 h / 20 °C 2.1: trifluoroacetic acid; triethylsilane / dichloromethane / 1 h 3.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 4.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C View Scheme
Multi-step reaction with 4 steps 1.1: methanesulfonyl chloride; triethylamine / dichloromethane / 0.02 h / 0 °C 1.2: 24 h / 20 °C 2.1: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h 3.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 4.1: sodium hydroxide; water / 1,4-dioxane / 24 h / 50 °C View Scheme

tert-butyl 4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazine-1-carboxylate (1228780-71-9) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: trifluoroacetic acid; triethylsilane / dichloromethane / 1 h 2.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 3.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C 3.2: Cooling View Scheme
Multi-step reaction with 3 steps 1: trifluoroacetic acid; triethylsilane / dichloromethane / 1 h 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 3: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C View Scheme
Multi-step reaction with 3 steps 1: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 3: sodium hydroxide; water / 1,4-dioxane / 24 h / 50 °C View Scheme

1-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1‘-biphenyl]-2-yl)methyl)piperazine (1228780-72-0) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 2.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C 2.2: Cooling View Scheme
Multi-step reaction with 2 steps 1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 2: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C View Scheme
Multi-step reaction with 2 steps 1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 2: sodium hydroxide; water / 1,4-dioxane / 24 h / 50 °C View Scheme

1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridin-5-ol (685514-01-6) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium phosphate / diethylene glycol dimethyl ether / 24 h / 115 °C 2.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 3.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C 3.2: Cooling View Scheme
Multi-step reaction with 3 steps 1: potassium phosphate / diethylene glycol dimethyl ether / 24 h / 115 °C 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 3: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C View Scheme
Multi-step reaction with 3 steps 1: potassium phosphate / diethylene glycol dimethyl ether / 24 h / 115 °C 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 3: sodium hydroxide; water / 1,4-dioxane / 24 h / 50 °C View Scheme
Multi-step reaction with 3 steps 1: potassium phosphate / diethylene glycol dimethyl ether / 24 h / 115 °C 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 3: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C View Scheme
Multi-step reaction with 3 steps 1: potassium phosphate / diethylene glycol dimethyl ether / 24 h / 115 °C 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 3: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C View Scheme

2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-fluorobenzoic acid methyl ester (1235865-75-4) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 2.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C 2.2: Cooling View Scheme
Multi-step reaction with 2 steps 1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 2: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C View Scheme
Multi-step reaction with 2 steps 1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 2: sodium hydroxide; water / 1,4-dioxane / 24 h / 50 °C View Scheme

2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-bromobenzoic acid tert-butyl ester → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium phosphate / toluene / 0.5 h 1.2: 16 h / 55 °C / Inert atmosphere 2.1: potassium tert-butylate / water; 2-methyltetrahydrofuran / 55 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1.1: tetrahydrofuran / 0 h / 20 - 25 °C 1.2: 60 - 65 °C 2.1: (4-(N,N-dimethylamino)phenyl)-di-tert-butylphosphine; tris-(dibenzylideneacetone)dipalladium(0); lithium hexamethyldisilazane / tetrahydrofuran; toluene / 0.5 h / 55 - 56 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: sodium t-butanolate; tris-(dibenzylideneacetone)dipalladium(0); (4-(N,N-dimethylamino)phenyl)-di-tert-butylphosphine / tetrahydrofuran; toluene / Inert atmosphere; Large scale 2: potassium tert-butylate / water; 2-methyltetrahydrofuran / 2 h / Inert atmosphere; Large scale View Scheme
Multi-step reaction with 2 steps 1.1: sodium t-butanolate / toluene; tetrahydrofuran / 0.75 h / 20 °C / Inert atmosphere 1.2: 18 h / 70 °C / Inert atmosphere 2.1: potassium tert-butylate; water / 2-methyltetrahydrofuran / 5 h / 50 °C / Inert atmosphere View Scheme

3,3-dimethylcyclohexanone (2979-19-3) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: trichlorophosphate / dichloromethane / 1.83 h / -5 - 20 °C 1.2: 21 h / 5 °C / Reflux 2.1: tetrabutylammomium bromide / acetonitrile / 0.08 h / 20 °C 2.2: 0.08 h / 20 °C 2.3: 15 h / 30 - 35 °C / Inert atmosphere 3.1: tetrahydrofuran; toluene / 0.08 h / 20 °C 3.2: 4 h / 25 °C 4.1: hydrogenchloride / water; isopropyl alcohol / 12 h / 65 °C 5.1: potassium phosphate / toluene / 0.5 h 5.2: 16 h / 55 °C / Inert atmosphere 6.1: potassium tert-butylate / water; 2-methyltetrahydrofuran / 55 °C / Inert atmosphere View Scheme
Multi-step reaction with 7 steps 1.1: sodium hydride / tetrahydrofuran / Reflux; Inert atmosphere 1.2: 4 h / Reflux 2.1: sodium hydride / dichloromethane / 0.83 h / 0 °C 2.2: -78 - 20 °C 3.1: tetrakis(triphenylphosphine) palladium(0); potassium fluoride / methanol; 1,2-dimethoxyethane / 16 h / 65 °C / Inert atmosphere 4.1: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / 20 °C / Inert atmosphere 5.1: triethylamine; methanesulfonyl chloride / dichloromethane / 0.05 h / 0 °C 5.2: 24 h / 0 °C 6.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 140 °C / Inert atmosphere 7.1: sodium hydroxide / tetrahydrofuran; methanol; water / 45 °C View Scheme
Multi-step reaction with 6 steps 1.1: trichlorophosphate / dichloromethane / 1 h / 0 - 20 °C 1.2: 0 - 50 °C 2.1: tetrabutylammomium bromide; potassium carbonate; palladium diacetate / tetrahydrofuran; water / 30 - 35 °C / Inert atmosphere 3.1: sodium tetrahydroborate; methanol / 2 h / 0 - 5 °C 4.1: phosphorus tribromide; pyridine / cyclohexane / 2 h / 2 - 5 °C 5.1: triethylamine / tetrahydrofuran / 3 h / 67 °C 6.1: sodium hydroxide; water / dimethyl sulfoxide / 3 h / 20 °C View Scheme

2-chloro-4,4-dimethyl-2-oxocyclohexenecarbaldehyde (1228943-80-3) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: tetrabutylammomium bromide / acetonitrile / 0.08 h / 20 °C 1.2: 0.08 h / 20 °C 1.3: 15 h / 30 - 35 °C / Inert atmosphere 2.1: tetrahydrofuran; toluene / 0.08 h / 20 °C 2.2: 4 h / 25 °C 3.1: hydrogenchloride / water; isopropyl alcohol / 12 h / 65 °C 4.1: potassium phosphate / toluene / 0.5 h 4.2: 16 h / 55 °C / Inert atmosphere 5.1: potassium tert-butylate / water; 2-methyltetrahydrofuran / 55 °C / Inert atmosphere View Scheme
Multi-step reaction with 5 steps 1: tetrabutylammomium bromide; potassium carbonate; palladium diacetate / tetrahydrofuran; water / 30 - 35 °C / Inert atmosphere 2: sodium tetrahydroborate; methanol / 2 h / 0 - 5 °C 3: phosphorus tribromide; pyridine / cyclohexane / 2 h / 2 - 5 °C 4: triethylamine / tetrahydrofuran / 3 h / 67 °C 5: sodium hydroxide; water / dimethyl sulfoxide / 3 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: potassium carbonate; tetrabutylammomium bromide; tetrakis(triphenylphosphine) palladium(0) / water; acetonitrile / 15 h / 60 °C / Inert atmosphere 2.1: sodium tris(acetoxy)borohydride / toluene; tetrahydrofuran / 8 h / 20 °C 2.2: 5 h / 70 °C 3.1: sodium t-butanolate / toluene; tetrahydrofuran / 0.75 h / 20 °C / Inert atmosphere 3.2: 18 h / 70 °C / Inert atmosphere 4.1: potassium tert-butylate; water / 2-methyltetrahydrofuran / 5 h / 50 °C / Inert atmosphere View Scheme

4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbaldehyde (1228837-05-5) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: tetrahydrofuran; toluene / 0.08 h / 20 °C 1.2: 4 h / 25 °C 2.1: hydrogenchloride / water; isopropyl alcohol / 12 h / 65 °C 3.1: potassium phosphate / toluene / 0.5 h 3.2: 16 h / 55 °C / Inert atmosphere 4.1: potassium tert-butylate / water; 2-methyltetrahydrofuran / 55 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1.1: tetrahydrofuran / 0.17 h / 32 °C 1.2: 20 h / 5 °C 2.1: water; lithium hydroxide / tetrahydrofuran / 64 h / 32 - 65 °C View Scheme
Multi-step reaction with 4 steps 1: sodium tetrahydroborate; methanol / 2 h / 0 - 5 °C 2: phosphorus tribromide; pyridine / cyclohexane / 2 h / 2 - 5 °C 3: triethylamine / tetrahydrofuran / 3 h / 67 °C 4: sodium hydroxide; water / dimethyl sulfoxide / 3 h / 20 °C View Scheme
Multi-step reaction with 5 steps 1: sodium tris(acetoxy)borohydride / tetrahydrofuran; toluene / 20 °C / Inert atmosphere; Large scale 2: hydrogenchloride / isopropyl alcohol; water / Inert atmosphere; Large scale 3: potassium phosphate / toluene; water / 0.5 h / 25 °C / Inert atmosphere 4: sodium t-butanolate; tris-(dibenzylideneacetone)dipalladium(0); (4-(N,N-dimethylamino)phenyl)-di-tert-butylphosphine / tetrahydrofuran; toluene / Inert atmosphere; Large scale 5: potassium tert-butylate / water; 2-methyltetrahydrofuran / 2 h / Inert atmosphere; Large scale View Scheme
Multi-step reaction with 3 steps 1.1: sodium tris(acetoxy)borohydride / toluene; tetrahydrofuran / 8 h / 20 °C 1.2: 5 h / 70 °C 2.1: sodium t-butanolate / toluene; tetrahydrofuran / 0.75 h / 20 °C / Inert atmosphere 2.2: 18 h / 70 °C / Inert atmosphere 3.1: potassium tert-butylate; water / 2-methyltetrahydrofuran / 5 h / 50 °C / Inert atmosphere View Scheme

4-bromo-2-fluoro-benzoic acid tert-butyl ester (889858-12-2) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium t-butanolate / N,N-dimethyl-formamide / 0 - 50 °C 2.1: potassium phosphate / toluene / 0.5 h 2.2: 16 h / 55 °C / Inert atmosphere 3.1: potassium tert-butylate / water; 2-methyltetrahydrofuran / 55 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: N,N-dimethyl-formamide; acetonitrile / 0 h / 20 - 25 °C 1.2: 24 h / 20 - 95 °C 2.1: tetrahydrofuran / 0 h / 20 - 25 °C 2.2: 60 - 65 °C 3.1: (4-(N,N-dimethylamino)phenyl)-di-tert-butylphosphine; tris-(dibenzylideneacetone)dipalladium(0); lithium hexamethyldisilazane / tetrahydrofuran; toluene / 0.5 h / 55 - 56 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: potassium tert-butylate / N,N-dimethyl-formamide / 8 h / 0 - 55 °C / Inert atmosphere; Large scale 2: sodium t-butanolate; tris-(dibenzylideneacetone)dipalladium(0); (4-(N,N-dimethylamino)phenyl)-di-tert-butylphosphine / tetrahydrofuran; toluene / Inert atmosphere; Large scale 3: potassium tert-butylate / water; 2-methyltetrahydrofuran / 2 h / Inert atmosphere; Large scale View Scheme
Multi-step reaction with 3 steps 1.1: potassium carbonate / 1-methyl-pyrrolidin-2-one / 10 h / 100 °C 2.1: sodium t-butanolate / toluene; tetrahydrofuran / 0.75 h / 20 °C / Inert atmosphere 2.2: 18 h / 70 °C / Inert atmosphere 3.1: potassium tert-butylate; water / 2-methyltetrahydrofuran / 5 h / 50 °C / Inert atmosphere View Scheme

1-bromo-3-fluoro-4-iodobenzene (105931-73-5) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: isopropylmagnesium chloride / tetrahydrofuran / 1 h / -5 - 0 °C 1.2: 1 h 2.1: sodium t-butanolate / N,N-dimethyl-formamide / 0 - 50 °C 3.1: potassium phosphate / toluene / 0.5 h 3.2: 16 h / 55 °C / Inert atmosphere 4.1: potassium tert-butylate / water; 2-methyltetrahydrofuran / 55 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: isopropylmagnesium chloride / tetrahydrofuran / 1 h / -5 - 0 °C / Inert atmosphere; Large scale 1.2: 1 h / 0 - 5 °C / Inert atmosphere; Large scale 2.1: potassium tert-butylate / N,N-dimethyl-formamide / 8 h / 0 - 55 °C / Inert atmosphere; Large scale 3.1: sodium t-butanolate; tris-(dibenzylideneacetone)dipalladium(0); (4-(N,N-dimethylamino)phenyl)-di-tert-butylphosphine / tetrahydrofuran; toluene / Inert atmosphere; Large scale 4.1: potassium tert-butylate / water; 2-methyltetrahydrofuran / 2 h / Inert atmosphere; Large scale View Scheme
Multi-step reaction with 4 steps 1.1: isopropylmagnesium chloride / tetrahydrofuran / 1 h / -10 - -5 °C 1.2: 1 h / -5 - 0 °C 2.1: potassium carbonate / 1-methyl-pyrrolidin-2-one / 10 h / 100 °C 3.1: sodium t-butanolate / toluene; tetrahydrofuran / 0.75 h / 20 °C / Inert atmosphere 3.2: 18 h / 70 °C / Inert atmosphere 4.1: potassium tert-butylate; water / 2-methyltetrahydrofuran / 5 h / 50 °C / Inert atmosphere View Scheme

4-Chlorophenylboronic acid (1679-18-1) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: cesium fluoride; tetrakis(triphenylphosphine) palladium(0) / methanol; 1,2-dimethoxyethane / 24 h / 70 °C 2.1: lithium borohydride; methanol / diethyl ether / 24 h / 20 °C 3.1: methanesulfonyl chloride; triethylamine / dichloromethane / 0.02 h / 0 °C 3.2: 24 h / 20 °C 4.1: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h 5.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 6.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C View Scheme

C16H21ClO3S → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 50 °C / Inert atmosphere 2: sodium hydroxide; water / tetrahydrofuran; ethanol / 20 °C View Scheme

2-fluoro-4-nitro-benzoic acid methyl ester (392-09-6) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 5 steps 1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 50 °C / Inert atmosphere 2: hydrogen; palladium 10% on activated carbon / methanol / 760.05 Torr 3: potassium carbonate / tert-butyl alcohol / 48 h 4: potassium carbonate / N,N-dimethyl-formamide / 50 °C / Inert atmosphere 5: sodium hydroxide; water / tetrahydrofuran; ethanol / 20 °C View Scheme

C15H11N3O5 → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: hydrogen; palladium 10% on activated carbon / methanol / 760.05 Torr 2: potassium carbonate / tert-butyl alcohol / 48 h 3: potassium carbonate / N,N-dimethyl-formamide / 50 °C / Inert atmosphere 4: sodium hydroxide; water / tetrahydrofuran; ethanol / 20 °C View Scheme

C15H13N3O3 → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / tert-butyl alcohol / 48 h 2: potassium carbonate / N,N-dimethyl-formamide / 50 °C / Inert atmosphere 3: sodium hydroxide; water / tetrahydrofuran; ethanol / 20 °C View Scheme

methyl (2-((1H-pyrrole[2,3-b]pyridin-5-yl)oxy)-4-(piperazin-1-yl))benzoate → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 50 °C / Inert atmosphere 2: sodium hydroxide; water / tetrahydrofuran; ethanol / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: tetrahydrofuran / 0.17 h / 32 °C 1.2: 20 h / 5 °C 2.1: water; lithium hydroxide / tetrahydrofuran / 64 h / 32 - 65 °C View Scheme
Multi-step reaction with 2 steps 1: triethylamine / tetrahydrofuran / 3 h / 67 °C 2: sodium hydroxide; water / dimethyl sulfoxide / 3 h / 20 °C View Scheme

5-hydroxypyrrolo[2,3-b]pyridine (98549-88-3) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 5 steps 1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 50 °C / Inert atmosphere 2: hydrogen; palladium 10% on activated carbon / methanol / 760.05 Torr 3: potassium carbonate / tert-butyl alcohol / 48 h 4: potassium carbonate / N,N-dimethyl-formamide / 50 °C / Inert atmosphere 5: sodium hydroxide; water / tetrahydrofuran; ethanol / 20 °C View Scheme
Multi-step reaction with 3 steps 1: potassium phosphate heptahydrate / diethylene glycol dimethyl ether / 115 °C / Inert atmosphere 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 140 °C / Inert atmosphere 3: sodium hydroxide / tetrahydrofuran; methanol; water / 45 °C View Scheme
Multi-step reaction with 2 steps 1.1: N,N-dimethyl-formamide; acetonitrile / 0 h / 20 - 25 °C 1.2: 26 h / 20 - 95 °C 1.3: 0.5 h / 60 - 95 °C 2.1: (4-(N,N-dimethylamino)phenyl)-di-tert-butylphosphine; tris-(dibenzylideneacetone)dipalladium(0); lithium hexamethyldisilazane / tetrahydrofuran; toluene / 0.5 h / 55 - 56 °C / Inert atmosphere View Scheme

methyl 2,4-difluorobenzoate (106614-28-2) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium phosphate heptahydrate / diethylene glycol dimethyl ether / 115 °C / Inert atmosphere 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 140 °C / Inert atmosphere 3: sodium hydroxide / tetrahydrofuran; methanol; water / 45 °C View Scheme
Multi-step reaction with 3 steps 1.1: potassium phosphate / 1,4-dioxane / 47 h / 34 - 90 °C 2.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 0.08 h / 29 °C / Inert atmosphere 2.2: 24.08 h / 29 - 120 °C 3.1: water; lithium hydroxide / tetrahydrofuran / 64 h / 32 - 65 °C View Scheme
Multi-step reaction with 4 steps 1: potassium phosphate / diethylene glycol dimethyl ether / 110 °C 2: dimethyl sulfoxide / 2 h / 90 °C 3: triethylamine / tetrahydrofuran / 3 h / 67 °C 4: sodium hydroxide; water / dimethyl sulfoxide / 3 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: potassium phosphate / diethylene glycol dimethyl ether / 10 h / 115 °C / Inert atmosphere 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 12 h / 140 °C / Inert atmosphere 3: sodium hydroxide; water / tetrahydrofuran; methanol / 10 h / 45 °C View Scheme

1-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1‘-biphenyl]-2-yl)methyl)piperazine (1228780-72-0) + 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-bromobenzoic acid → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); (4-(N,N-dimethylamino)phenyl)-di-tert-butylphosphine; lithium hexamethyldisilazane In tetrahydrofuran; toluene at 55 - 56℃; for 0.5h; Inert atmosphere;

1-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl) piperazine dihydrochloride → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium phosphate / toluene; water / 0 h / 20 - 25 °C 2: (4-(N,N-dimethylamino)phenyl)-di-tert-butylphosphine; tris-(dibenzylideneacetone)dipalladium(0); lithium hexamethyldisilazane / tetrahydrofuran; toluene / 0.5 h / 55 - 56 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: potassium phosphate / toluene; water / 0.5 h / 25 °C / Inert atmosphere 2: sodium t-butanolate; tris-(dibenzylideneacetone)dipalladium(0); (4-(N,N-dimethylamino)phenyl)-di-tert-butylphosphine / tetrahydrofuran; toluene / Inert atmosphere; Large scale 3: potassium tert-butylate / water; 2-methyltetrahydrofuran / 2 h / Inert atmosphere; Large scale View Scheme

methyl 4-bromo-2-fluorobenzoate (179232-29-2) → [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: N,N-dimethyl-formamide; acetonitrile / 0 h / 20 - 25 °C 1.2: 26 h / 20 - 95 °C 1.3: 0.5 h / 60 - 95 °C 2.1: (4-(N,N-dimethylamino)phenyl)-di-tert-butylphosphine; tris-(dibenzylideneacetone)dipalladium(0); lithium hexamethyldisilazane / tetrahydrofuran; toluene / 0.5 h / 55 - 56 °C / Inert atmosphere View Scheme

4-fluoro-3-nitrobenzenesulfonamide (406233-31-6) + [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) → 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-fluoro-3-nitrophenyl)sulfonyl)benzamide

Conditions	Yield
With trichlorophosphate at 85℃; for 5h;	100%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20 - 30℃; for 16h; Solvent; Temperature; Reagent/catalyst;	96.3%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + 4-Chloro-3-nitrobenzenesulfonamide (97-09-6) → 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-[(3-nitro-4-chlorophenyl)sulfonyl]-2-{1H-pyrrolo[2,3-b]pyridin-5-yloxy}benzamide (1257044-99-7)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20 - 30℃; for 16h;	96.8%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) → 2-[(1H-pyrrolo[2,3-b]pyridine-5-yl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl]methyl]piperazin-1-yl]benzoic acid sulfate

Conditions	Yield
With sulfuric acid In tetrahydrofuran at 50 - 55℃; for 0.5h;	92%

3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)benzenesulfonamide (1228779-96-1) + [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) → 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide (1257044-40-8)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 3h; Reagent/catalyst; Temperature;	91.4%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 25℃; for 12h; Inert atmosphere; Large scale;	86%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 25℃;	84%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + toluene-4-sulfonic acid (104-15-4) → 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro[1,1‘-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid p-toluenesulfonic acid salt

Conditions	Yield
In acetone at 20 - 30℃;	86.92%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + trifluoroacetic acid (76-05-1) → 2-[(1H-pyrrolo[2,3-b]pyridine-5-yl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl]methyl]piperazin-1-yl]benzoic acid trifluoroacetic acid salt

Conditions	Yield
In tetrahydrofuran at 50 - 55℃; for 0.5h;	85%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + 8-(2-nitro-4-aminosulfonylphenylamino)octanoic acid ethyl ester → ethyl 8-((4-(N-(2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)amino)octanoate

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h;	85%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h;	85%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + C17H26N4O6S → tert-butyl 4-((4-(N-(2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenylamino)methyl)piperidine-1-carboxylate

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃;	79%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + 6-(2-nitro-4-sulfamoylphenoxy)-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester → 6-(4-(N-(2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenoxy)-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 16h;	77.07%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + 3-nitro-4-((((2R,3R,4R,5R)-3,4,5-tris((trimethylsilyl)oxy)tetrahydrofuran-2-yl)methyl)amino)benzenesulfonamide → C44H48ClN7O10S

Conditions

Yield

Stage #1: [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid]; 3-nitro-4-((((2R,3R,4R,5R)-3,4,5-tris((trimethylsilyl)oxy)tetrahydrofuran-2-yl)methyl)amino)benzenesulfonamide With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; Stage #2: With acetic acid; N,N`-dimethylethylenediamine In dichloromethane at 55℃;

63%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + N-cyclohexyl-cyclohexanamine (101-83-7) → 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro[1,1‘-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid dicyclohexylamine salt

Conditions	Yield
In methanol; acetone at 20 - 30℃;	60.6%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + C32H46N4O12S → C65H79ClN8O14S

Conditions	Yield
Stage #1: [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] With 4-pyrrolidin-1-ylpyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane for 0.5h; Cooling with ice; Stage #2: C32H46N4O12S In dichloromethane at 20℃; for 24h;	58.1%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) → sodium 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4-chloro-5,5-dimethyl-3,4,5,6-tetrahydro[1,1‘-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoate

Conditions	Yield
With sodium 2-ethylhexenoate In ethyl acetate at 20 - 30℃; for 16h;	57.08%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + 2-nitro-4-sulfamoylphenyl trifluoromethanesulfonate → 4-(N-(2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl trifluoromethanesulfonate

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 3h;	53.9%

3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)benzenesulfonamide (1228779-96-1) + [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) → venetoclax sodium

Conditions	Yield
Stage #1: 3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)benzenesulfonamide; [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; Stage #2: With sodium hydroxide In methanol at 55 - 60℃; for 2h;	53%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + 4-(2-(4-oxaspiro[2.4]heptan-6-yloxy)ethoxy)-3-nitrobenzenesulfonamide → 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-N-((4-(2-(4-oxaspiro[2.4]heptan-6-yloxy)ethoxy)-3-nitrophenyl)sulfonyl)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-yl)benzamide

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃;	49%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + C27H38N4O11S → C60H71ClN8O13S

Conditions	Yield
Stage #1: [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] With 4-pyrrolidin-1-ylpyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane for 0.5h; Cooling with ice; Stage #2: C27H38N4O11S In dichloromethane at 20℃; for 24h;	47.8%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + (2-nitro-4-sulfamoylphenyl)glycine methyl ester → (4-(N-(2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyltetrahydro-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-nitrophenyl)glycine ethyl ester

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 12h;	47.4%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + C33H46N4O14S → C66H79ClN8O16S

Conditions	Yield
Stage #1: [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] With 4-pyrrolidin-1-ylpyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane for 0.5h; Cooling with ice; Stage #2: C33H46N4O14S In dichloromethane at 20℃; for 24h;	40.4%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + 4-((4-oxaspiro[2.4]heptan-6-yl)oxy)-3-nitrobenzenesulfonamide → 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-N-((4-(4-oxaspiro[2.4]heptan-6-yloxy)3-nitrophenyl)sulfonyl)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-yl)benzamide

Conditions	Yield
With dmap In dichloromethane at 0 - 20℃;	35%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + C12H15(2)H2N3O5S → C45H48(2)H2ClN7O7S

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 10h;	33%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + C19H31N5O6S → C52H64ClN9O8S

Conditions	Yield
Stage #1: [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #2: C19H31N5O6S In dichloromethane at 0 - 20℃; Inert atmosphere;	11%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + C19H26N6O4S → C52H59ClN10O6S

Conditions	Yield
Stage #1: [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #2: C19H26N6O4S In dichloromethane at 0 - 20℃; Inert atmosphere;	10%

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + (R)-3-nitro-4-(1-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-ylamino)benzenesulfonamide (1257046-28-8) → 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-[(3-nitro-4-{[(3R)-1-tetrahydro-2H-pyran-4-ylpyrrolidin-3-yl]amino}phenyl)sulfonyl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide (1257046-27-7)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane; N,N-dimethyl-formamide for 18h;
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane; N,N-dimethyl-formamide for 18h;

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + 5-chloro-6-((4-fluoro-1-(oxetan-3-yl)piperidin-4-yl)methoxy)pyridine-3-sulfonamide (1256546-39-0) → N-[(5-chloro-6-{[4-fluoro-1-(oxetan-3-yl)piperidin-4-yl]methoxy}pyridin-3-yl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide (1257049-26-5)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + (S)-3-nitro-4-((tetrahydro-2H-pyran-3-yl)methylamino)benzenesulfonamide (1228836-22-3) → 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-[(3-nitro-4-{[(3S)-tetrahydro-2H-pyran-3-ylmethyl]amino}phenyl)sulfonyl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide (1257044-51-1)

Conditions	Yield
Stage #1: [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid]; (S)-3-nitro-4-((tetrahydro-2H-pyran-3-yl)methylamino)benzenesulfonamide With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; Stage #2: With trifluoroacetic acid In water; acetonitrile Stage #3: With sodium hydrogencarbonate In dichloromethane; water
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;

[2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] (1235865-77-6) + 4-((((1r,4r)-4-hydroxy-4-methylcyclohexyl)methyl)amino)-3-nitrobenzenesulfonamide → 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-[(4-{[(trans-4-hydroxy-4-methylcyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane

Upstream product

• 183208-35-7 5-bromo-1H-pyrrolo[2,3-b]pyridine 
• 637-87-6 1-Chloro-4-iodobenzene 
• 195062-61-4 4-chlorophenylboronic acid pinacol ester 
• 1583-58-0 2,4-difluoro-benzoic acid 
• 183208-36-8 5-methoxy-1H-pyrrolo[2,3-b]pyridine 
• 1228837-05-5 4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbaldehyde 
• 105942-08-3 4-bromo-6-fluorobenzonitrile 
• 98549-88-3 5-hydroxypyrrolo[2,3-b]pyridine 
• 1228780-72-0 1-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1‘-biphenyl]-2-yl)methyl)piperazine 
• 179232-29-2 methyl 4-bromo-2-fluorobenzoate 
• 1628047-87-9 1-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl) piperazine dihydrochloride 
• 106614-28-2 methyl 2,4-difluorobenzoate 
• 1257044-57-7 methyl (2-((1H-pyrrole[2,3-b]pyridin-5-yl)oxy)-4-(piperazin-1-yl))benzoate 

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