1235865-76-5

Basic information

• Product Name: Methyl 2-[(1H-pyrrolo[2,3-b]pyridin-5-yl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl]methyl]piperazin-1-yl]benzoate
• Synonyms: Methyl 2-[(1H-pyrrolo[2,3-b]pyridin-5-yl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl]methyl]piperazin-1-yl]benzoate;Venetoclax highstage intermediate;methyl 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
• CAS NO: 1235865-76-5
• Molecular Formula: C₃₄H₃₇ClN₄O₃
• Molecular Weight: 585.13558
• Mol File: 1235865-76-5.mol
• Article Data: 17

Chemical Properties

• Appearance: /
• Density: 1.242±0.06 g/cm3(Predicted)
• PKA: 13.26±0.40(Predicted)
• CAS DataBase Reference: Methyl 2-[(1H-pyrrolo[2,3-b]pyridin-5-yl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl]methyl]piperazin-1-yl]benzoate(CAS DataBase Reference)
• NIST Chemistry Reference: Methyl 2-[(1H-pyrrolo[2,3-b]pyridin-5-yl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl]methyl]piperazin-1-yl]benzoate(1235865-76-5)
• EPA Substance Registry System: Methyl 2-[(1H-pyrrolo[2,3-b]pyridin-5-yl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl]methyl]piperazin-1-yl]benzoate(1235865-76-5)

Safety Data

• Hazardous Substances Data: 1235865-76-5(Hazardous Substances Data)

Usage

General Description

Methyl 2-[(1H-pyrrolo[2,3-b]pyridin-5-yl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl]methyl]piperazin-1-yl]benzoate is a chemical compound with a complex structure. It contains a pyrrolopyridine ring and a benzene ring, as well as a piperazine ring and a methyl ester group. The compound also includes a chlorophenyl group and a cyclohexenyl group. This chemical is likely to have pharmaceutical applications due to the presence of the piperazine moiety, which is a common structural feature in many drug molecules. The compound's unique structure may also make it suitable for use in medicinal chemistry or as a reference compound in chemical analysis.

Synthetic route

methyl (2-((1H-pyrrole[2,3-b]pyridin-5-yl)oxy)-4-(piperazin-1-yl))benzoate + 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 methyl ester (1235865-76-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 50℃; Inert atmosphere;	88%

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-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 methyl ester (1235865-76-5)

Conditions	Yield
With dipotassium hydrogenphosphate In dimethyl sulfoxide at 140℃; for 12h; Inert atmosphere;	76%
With dipotassium hydrogenphosphate In dimethyl sulfoxide at 140℃; Inert atmosphere;	51%
With dipotassium hydrogenphosphate In dimethyl sulfoxide at 135℃; for 24h;

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 methyl ester (1235865-76-5)

Conditions	Yield
With copper(l) iodide; t-butyl malonate; caesium carbonate In dimethyl sulfoxide at 120℃; for 12h; Solvent; Reagent/catalyst; Inert atmosphere;	75%

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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 4 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 View Scheme
Multi-step reaction with 4 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 View Scheme
Multi-step reaction with 4 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 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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 3 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 View Scheme
Multi-step reaction with 3 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 View Scheme
Multi-step reaction with 3 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 View Scheme
Multi-step reaction with 3 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 View Scheme
Multi-step reaction with 3 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 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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 6 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 View Scheme
Multi-step reaction with 6 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 View Scheme
Multi-step reaction with 6 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 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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 5 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 View Scheme
Multi-step reaction with 5 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 View Scheme
Multi-step reaction with 5 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 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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 4 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 View Scheme
Multi-step reaction with 4 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 View Scheme
Multi-step reaction with 4 steps 1.1: lithium borohydride; methanol / diethyl ether / 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 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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 3 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 View Scheme
Multi-step reaction with 3 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 View Scheme
Multi-step reaction with 3 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 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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: trifluoroacetic acid; triethylsilane / dichloromethane / 1 h 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C View Scheme
Multi-step reaction with 2 steps 1: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C View Scheme
Multi-step reaction with 2 steps 1: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C View Scheme
Multi-step reaction with 2 steps 1: hydrogenchloride / ethyl acetate; dichloromethane / 3 h / 0 - 20 °C 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 12 h / 140 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: trifluoroacetic acid; triethylsilane / dichloromethane / 1 h 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium phosphate / diethylene glycol dimethyl ether / 24 h / 115 °C 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C View Scheme
Multi-step reaction with 2 steps 1: potassium phosphate / diethylene glycol dimethyl ether / 24 h / 115 °C 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C View Scheme
Multi-step reaction with 2 steps 1: potassium phosphate / diethylene glycol dimethyl ether / 24 h / 115 °C 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 24 h / 135 °C 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 methyl ester (1235865-76-5)

Conditions

Yield

Multi-step reaction with 5 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 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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 4 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 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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 3 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 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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / tert-butyl alcohol / 48 h 2: potassium carbonate / N,N-dimethyl-formamide / 50 °C / Inert atmosphere 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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 4 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 View Scheme
Multi-step reaction with 2 steps 1: potassium phosphate heptahydrate / diethylene glycol dimethyl ether / 115 °C / Inert atmosphere 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 140 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 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 View Scheme
Multi-step reaction with 3 steps 1: potassium phosphate / diethylene glycol dimethyl ether / 110 °C 2: dimethyl sulfoxide / 2 h / 90 °C 3: triethylamine / tetrahydrofuran / 3 h / 67 °C View Scheme
Multi-step reaction with 2 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 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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium phosphate heptahydrate / diethylene glycol dimethyl ether / 115 °C / Inert atmosphere 2: dipotassium hydrogenphosphate / dimethyl sulfoxide / 140 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 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 View Scheme
Multi-step reaction with 3 steps 1: potassium phosphate / diethylene glycol dimethyl ether / 110 °C 2: dimethyl sulfoxide / 2 h / 90 °C 3: triethylamine / tetrahydrofuran / 3 h / 67 °C View Scheme
Multi-step reaction with 2 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 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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 6 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 View Scheme
Multi-step reaction with 5 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 View Scheme
Multi-step reaction with 8 steps 1.1: sodium hydride / tetrahydrofuran / 4 h / Inert atmosphere; Reflux 2.1: sodium hydride / dichloromethane / 0.5 h / 0 °C 2.2: -25 - 20 °C 3.1: tetrakis(triphenylphosphine) palladium(0); potassium fluoride / dichloromethane; methanol / 6 h / 65 °C / Inert atmosphere 4.1: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 0 °C 5.1: 1H-imidazole; triphenylphosphine; iodine / acetonitrile; diethyl ether / 1 h / -5 °C 6.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 80 °C 7.1: hydrogenchloride / ethyl acetate; dichloromethane / 3 h / 0 - 20 °C 8.1: dipotassium hydrogenphosphate / dimethyl sulfoxide / 12 h / 140 °C / Inert atmosphere View Scheme

2,4-difluoro-benzoic acid (1583-58-0) → 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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: sodium hydroxide / dimethyl sulfoxide / 8 h / 130 °C 2: thionyl chloride / 5 h / 60 °C 3: dimethyl sulfoxide / 5 h / 20 °C 4: sodium tris(acetoxy)borohydride / dichloromethane / 5 h / 30 °C 5: caesium carbonate; copper(l) iodide; t-butyl malonate / dimethyl sulfoxide / 12 h / 120 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1: sulfuric acid / 8 h / 60 °C 2: potassium phosphate / diethylene glycol dimethyl ether / 110 °C 3: dimethyl sulfoxide / 2 h / 90 °C 4: triethylamine / tetrahydrofuran / 3 h / 67 °C View Scheme

4-fluorosalicylic acid (345-29-9) → 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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: thionyl chloride / 5 h / 60 °C 2: dimethyl sulfoxide / 5 h / 20 °C 3: sodium tris(acetoxy)borohydride / dichloromethane / 5 h / 30 °C 4: caesium carbonate; copper(l) iodide; t-butyl malonate / dimethyl sulfoxide / 12 h / 120 °C / Inert atmosphere View Scheme

methyl 4-fluoro-2-hydroxybenzoate (392-04-1) → 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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: dimethyl sulfoxide / 5 h / 20 °C 2: sodium tris(acetoxy)borohydride / dichloromethane / 5 h / 30 °C 3: caesium carbonate; copper(l) iodide; t-butyl malonate / dimethyl sulfoxide / 12 h / 120 °C / Inert atmosphere View Scheme

4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbaldehyde (1228837-05-5) + 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 methyl ester (1235865-76-5)

Conditions	Yield
Stage #1: 4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbaldehyde; methyl 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(piperazin-1-yl)benzoate In tetrahydrofuran at 32℃; for 0.166667h; Stage #2: With sodium tris(acetoxy)borohydride In tetrahydrofuran at 5℃; for 20h;	48.2 mg

5-methoxy-1H-pyrrolo[2,3-b]pyridine (183208-36-8) → 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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: boron tribromide / dichloromethane / 4 h / 0 - 27 °C 2: potassium phosphate / diethylene glycol dimethyl ether / 110 °C 3: dimethyl sulfoxide / 2 h / 90 °C 4: triethylamine / tetrahydrofuran / 3 h / 67 °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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: dimethyl sulfoxide / 2 h / 90 °C 2: triethylamine / tetrahydrofuran / 3 h / 67 °C View Scheme

methyl (2-((1H-pyrrole[2,3-b]pyridin-5-yl)oxy)-4-(piperazin-1-yl))benzoate + 1-(2-(bromomethyl)-5,5-dimethylcyclohex-1-enyl)-4-chlorobenzene → 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)

Conditions	Yield
With triethylamine In tetrahydrofuran at 67℃; for 3h;	127 g

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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 4 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 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 methyl ester (1235865-76-5)

Conditions	Yield
Multi-step reaction with 3 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 View Scheme

4-chlorophenylboronic acid pinacol ester (195062-61-4) → 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 methyl ester (1235865-76-5)

Conditions

Yield

Multi-step reaction with 6 steps 1: tetrakis(triphenylphosphine) palladium(0); potassium fluoride / dichloromethane; methanol / 6 h / 65 °C / Inert atmosphere 2: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 0 °C 3: 1H-imidazole; triphenylphosphine; iodine / acetonitrile; diethyl ether / 1 h / -5 °C 4: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 80 °C 5: hydrogenchloride / ethyl acetate; dichloromethane / 3 h / 0 - 20 °C 6: dipotassium hydrogenphosphate / dimethyl sulfoxide / 12 h / 140 °C / Inert atmosphere View Scheme

4'-chloro-6-(iodomethyl)-3,3-dimethyl-2,3,4,5-tetrahydro-1,1'-biphenyl → 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)

Conditions	Yield
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 80 °C 2: hydrogenchloride / ethyl acetate; dichloromethane / 3 h / 0 - 20 °C 3: dipotassium hydrogenphosphate / dimethyl sulfoxide / 12 h / 140 °C / Inert atmosphere View Scheme

1-Chloro-4-iodobenzene (637-87-6) → 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 methyl ester (1235865-76-5)

Conditions

Yield

Multi-step reaction with 7 steps 1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate / dimethyl sulfoxide / 10 h / 95 °C / Inert atmosphere 2: tetrakis(triphenylphosphine) palladium(0); potassium fluoride / dichloromethane; methanol / 6 h / 65 °C / Inert atmosphere 3: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 0 °C 4: 1H-imidazole; triphenylphosphine; iodine / acetonitrile; diethyl ether / 1 h / -5 °C 5: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 80 °C 6: hydrogenchloride / ethyl acetate; dichloromethane / 3 h / 0 - 20 °C 7: dipotassium hydrogenphosphate / dimethyl sulfoxide / 12 h / 140 °C / Inert atmosphere View Scheme

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%

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)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide (1257044-40-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C 1.2: Cooling 2.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 24 h View Scheme
Multi-step reaction with 2 steps 1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C 2: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 20 °C View Scheme
Multi-step reaction with 2 steps 1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C 2: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 24 h View Scheme

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) → trans-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-[(4-{[(4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C 1.2: Cooling 2.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane View Scheme

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) → {5-[5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-{[(4-{[(trans-4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]carbamoyl}phenoxy]-7H-pyrrolo[2,3-b]pyridin-7-yl}methyl dihydrogen phosphate trifluoroacetate

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C 1.2: Cooling 2.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane 3.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 1.5 h / 80 °C / microwave irradiation 4.1: dichloromethane / 1 h View Scheme

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) → C56H73ClN7O11PS

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C 1.2: Cooling 2.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane 3.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 1.5 h / 80 °C / microwave irradiation View Scheme

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) → 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide hydrochloride

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C 2: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 20 °C 3: hydrogenchloride / acetonitrile; water View Scheme

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) → 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide sulfate (1379647-80-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide / 1,4-dioxane / 24 h / 50 °C 2: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 20 °C 3: sulfuric acid / isopropyl alcohol / 70 °C View Scheme

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) → 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-[(4-{[(2R)-1,4-dioxan-2-ylmethyl]amino}-3-nitrophenyl)sulfonyl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydroxide; water / 1,4-dioxane / 24 h / 50 °C 2.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane 2.2: 1.5 h View Scheme

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)piperazine-1-yl)-N-((3-nitro-4-(3-((tetrahydro-2H-pyran-4-yl)oxy)prop-1-yn-1-yl)phenyl)sulfonyl)benzamide

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide / tetrahydrofuran; methanol; water / 45 °C 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane / 3 h / 20 °C 3: triethylamine; bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide / N,N-dimethyl-formamide / 60 °C View Scheme

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)-N-((3-nitro-4-((2-(tetrahydro-2H-pyran-4-yl)-2-azaspiro[3.3]heptan-6-yl)oxy)phenyl)sulfonyl)benzamide

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium hydroxide / tetrahydrofuran; methanol; water / 45 °C 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane / 16 h / 20 °C 3: trifluoroacetic acid / dichloromethane / 3 h / 20 °C 4: sodium tris(acetoxy)borohydride / methanol; dichloromethane / 0.25 h / 20 °C View Scheme

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) → C50H57ClN8O7S

Conditions	Yield
Multi-step reaction with 5 steps 1: sodium hydroxide / tetrahydrofuran; methanol; water / 45 °C 2: trichlorophosphate / 5 h / 85 °C 3: triethylamine / tetrahydrofuran / 20 °C 4: trifluoroacetic acid / dichloromethane / 20 °C 5: sodium tris(acetoxy)borohydride; sodium acetate / methanol; dichloromethane / 20 °C View Scheme

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) → 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
Multi-step reaction with 2 steps 1: sodium hydroxide / tetrahydrofuran; methanol; water / 45 °C 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane / 16 h / 20 °C View Scheme

Upstream product

• 183208-35-7 5-bromo-1H-pyrrolo[2,3-b]pyridine 
• 858116-66-2 5-bromo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine 
• 32767-46-7 methyl 4,4-dimethyl-2-oxocyclohexancarboxylate 
• 179232-29-2 methyl 4-bromo-2-fluorobenzoate 
• 1235865-75-4 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-fluorobenzoic acid methyl ester 
• 1628047-87-9 1-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl) piperazine dihydrochloride 
• 1228780-72-0 1-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1‘-biphenyl]-2-yl)methyl)piperazine 
• 637-87-6 1-Chloro-4-iodobenzene 
• 195062-61-4 4-chlorophenylboronic acid pinacol ester 
• 1228837-05-5 4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbaldehyde 
• 1228943-80-3 2-chloro-4,4-dimethyl-2-oxocyclohexenecarbaldehyde 
• 1257044-57-7 methyl (2-((1H-pyrrole[2,3-b]pyridin-5-yl)oxy)-4-(piperazin-1-yl))benzoate 
• 183208-36-8 5-methoxy-1H-pyrrolo[2,3-b]pyridine 
• 392-04-1 methyl 4-fluoro-2-hydroxybenzoate 

Downstream Products

• 1257044-40-8 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)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide 

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