877399-74-1

Basic information

• Product Name: tert-Butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate
• Synonyms: tert-Butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate;4-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester;1-Piperidinecarboxylic acid, 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]-, 1,1-dimethylethyl ester;1-(1-Boc-4-piperidyl)pyrazole-4-boronic acid pinacol ester;4-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester;4-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl)piperidine-1-carb;tert-butyl 4-(4-(4,4,5,5-tetraMethyl-1,3,2-dioxaborolan-2-yl)-1H;1-Piperidinecarboxylic acid, 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1h-pyrazol-1-yl]-, 196%
• CAS NO: 877399-74-1
• Molecular Formula: C₁₉H₃₂BN₃O₄
• Molecular Weight: 377.29
• EINECS: 1308068-626-2
• Mol File: 877399-74-1.mol
• Article Data: 54

Chemical Properties

• Melting Point: 114.0 to 118.0 °C
• Boiling Point: 492.803 °C at 760 mmHg
• Flash Point: 251.838 °C
• Appearance: /
• Density: 1.14 g/cm³
• Refractive Index: 1.539
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• PKA: 2.89±0.19(Predicted)
• CAS DataBase Reference: tert-Butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: tert-Butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate(877399-74-1)
• EPA Substance Registry System: tert-Butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate(877399-74-1)

Safety Data

• Hazardous Substances Data: 877399-74-1(Hazardous Substances Data)

Usage

General Description

Tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate is a chemical compound with a complex structure. It contains a piperidine-1-carboxylate group attached to a pyrazol-1-yl group, which is further linked to a dioxaborolan-2-yl group. The presence of the tert-butyl group and the tetramethyl groups in the dioxaborolan ring contribute to its sterically hindered nature. tert-Butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate is commonly used in organic synthesis and pharmaceutical research as a reagent or intermediate compound for the production of various pharmaceuticals and other organic molecules. Its unique structure and functional groups make it a valuable building block for synthesizing complex organic compounds.

InChI:InChI=1/C19H32BN3O4/c1-17(2,3)25-16(24)22-10-8-15(9-11-22)23-13-14(12-21-23)20-26-18(4,5)19(6,7)27-20/h12-13,15H,8-11H2,1-7H3

Synthetic route

4-(4-bromo-1H-pyrazol-1-yl)piperidine-1-carboxylic acid tert-butyl ester (877399-50-3) + bis(pinacol)diborane (73183-34-3) → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
With C54H44NO2PPdS; potassium acetate In tetrahydrofuran at 80℃; for 24h; Miyaura Borylation Reaction; Inert atmosphere; Sealed tube;	94%
With isopropylmagnesium chloride In tetrahydrofuran at -10 - 30℃; for 9h; Inert atmosphere; Large scale;	81%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In dimethyl sulfoxide at 80℃; for 0.166667h; Inert atmosphere;	44%

tert-butyl 4-(4-iodo-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-73-0) + bis(pinacol)diborane (73183-34-3) → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; potassium acetate In dimethyl sulfoxide at 80℃; for 2h; Inert atmosphere;	87.9%
With bis-triphenylphosphine-palladium(II) chloride; potassium acetate In dimethyl sulfoxide at 80℃; for 2h; Inert atmosphere;	87.9%
With potassium acetate; tetrakis(triphenylphosphine) palladium(0) In dimethyl sulfoxide at 80℃; for 2h; Inert atmosphere;	83%

tert-butyl 4-(4-iodo-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-73-0) + 2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1195-66-0) → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
Stage #1: tert-butyl 4-(4-iodo-1H-pyrazol-1-yl)piperidine-1-carboxylate With isopropylmagnesium chloride In tetrahydrofuran at -10 - 0℃; for 5.25h; Large scale reaction; Stage #2: 2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane In tetrahydrofuran at 20 - 25℃; for 10.75h; Large scale reaction;	81%
Stage #1: tert-butyl 4-(4-iodo-1H-pyrazol-1-yl)piperidine-1-carboxylate With isopropylmagnesium chloride In tetrahydrofuran at -10 - 20℃; for 2h; Inert atmosphere; Stage #2: 2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane In tetrahydrofuran at 20℃; for 12h; Inert atmosphere;	61.5%
With isopropylmagnesium chloride In tetrahydrofuran at 0 - 30℃;
In tetrahydrofuran

4-(4-bromo-1H-pyrazol-1-yl)piperidine-1-carboxylic acid tert-butyl ester (877399-50-3) + 2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1195-66-0) → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
Stage #1: 4-(4-bromo-1H-pyrazol-1-yl)piperidine-1-carboxylic acid tert-butyl ester With isopropylmagnesium chloride; lithium chloride In tetrahydrofuran at 20 - 30℃; for 12h; Stage #2: 2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane In tetrahydrofuran at 20 - 30℃; for 6h;	80%

4-(4-bromo-1H-pyrazol-1-yl)piperidine-1-carboxylic acid tert-butyl ester (877399-50-3) + dimethylphenyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)silane (185990-03-8) → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
With potassium methanolate In 1,2-dimethoxyethane at 30℃; for 1h;	61%

4-(4-bromo-1H-pyrazol-1-yl)piperidine-1-carboxylic acid tert-butyl ester (877399-50-3) + 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (61676-62-8) → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
Stage #1: 4-(4-bromo-1H-pyrazol-1-yl)piperidine-1-carboxylic acid tert-butyl ester With isopropylmagnesium chloride; lithium chloride In tetrahydrofuran at 20 - 30℃; for 12h; Stage #2: 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane In tetrahydrofuran at 20 - 30℃; for 6h;	60%
With n-butyllithium In tetrahydrofuran; hexane at -70 - 20℃; for 3h;	51%

pyrazole-4-boronic acid pinacol ester (269410-08-4) + 1-(tert-butoxycarbonyl)piperidin-4-yl methanesulfonate (141699-59-4) → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 20 - 100℃; for 18h;	48%
With caesium carbonate In N,N-dimethyl-formamide at 90℃; Inert atmosphere;	44%
With caesium carbonate In N,N-dimethyl-formamide at 100℃; for 24h;	39%

1-(tert-butoxycarbonyl)piperidin-4-yl methanesulfonate (141699-59-4) → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
Stage #1: pyrazole-4-boronic acid pinacol ester With sodium hydride In N,N-dimethyl-formamide at 0℃; for 1h; Stage #2: 1-(tert-butoxycarbonyl)piperidin-4-yl methanesulfonate In N,N-dimethyl-formamide at 100℃;	29%
Multi-step reaction with 2 steps 1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 110 °C / Inert atmosphere; Microwave irradiation 2: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate / dimethyl sulfoxide / 3 h / 80 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 1 h / 4 °C / Inert atmosphere 1.2: 12 h / 100 °C / Inert atmosphere 2.1: bis-triphenylphosphine-palladium(II) chloride; potassium acetate / dimethyl sulfoxide / 2 h / 80 °C / Inert atmosphere View Scheme

pyrazole-4-boronic acid pinacol ester (269410-08-4) + tert-butyl 4-bromo-1-piperidinecarboxylate (180695-79-8) → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
With caesium carbonate In N,N-dimethyl acetamide at 85℃; for 12h; Inert atmosphere;	5%

t-butyl 4-hydroxy piperidine-1-carboxylate (109384-19-2) → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 0 - 20 °C / Inert atmosphere 2: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 110 °C / Inert atmosphere; Microwave irradiation 3: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate / dimethyl sulfoxide / 3 h / 80 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: dmap; triethylamine / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: sodium hydride / N,N-dimethyl-formamide / 1 h / 4 °C / Inert atmosphere 2.2: 12 h / 100 °C / Inert atmosphere 3.1: bis-triphenylphosphine-palladium(II) chloride; potassium acetate / dimethyl sulfoxide / 2 h / 80 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: triethylamine / tert-butyl methyl ether / 1 h / -5 - 22 °C / Inert atmosphere 2.1: caesium carbonate / n-methyl-2-pyrrilidone / 18.5 h / 80 °C 3.1: isopropylmagnesium chloride / tetrahydrofuran / 5.25 h / -10 - 0 °C / Large scale reaction 3.2: 10.75 h / 20 - 25 °C / Large scale reaction View Scheme

4-HYDROXYPIPERIDINE (5382-16-1) → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 1 h / 0 - 20 °C 2: triethylamine / dichloromethane / 3 h / 0 - 20 °C 3: sodium hydride / N,N-dimethyl-formamide / 12 h / 80 °C 4: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane / 12 h / 110 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1: triethylamine 2: triethylamine; dmap / dichloromethane 3: sodium hydride / N,N-dimethyl-formamide 4: tetrahydrofuran View Scheme
Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 1 h / 0 - 20 °C 2: triethylamine / dichloromethane / 3 h / 0 - 20 °C 3: sodium hydride / N,N-dimethyl-formamide; mineral oil / 12 h / 80 °C 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere; Sealed tube View Scheme

di-tert-butyl dicarbonate (24424-99-5) → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 1 h / 0 - 20 °C 2: triethylamine / dichloromethane / 3 h / 0 - 20 °C 3: sodium hydride / N,N-dimethyl-formamide / 12 h / 80 °C 4: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane / 12 h / 110 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 1 h / 0 - 20 °C 2: triethylamine / dichloromethane / 3 h / 0 - 20 °C 3: sodium hydride / N,N-dimethyl-formamide; mineral oil / 12 h / 80 °C 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 12 h / 100 °C / Inert atmosphere; Sealed tube View Scheme

bis(pinacol)diborane (73183-34-3) → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 3,4,7,8-Tetramethyl-o-phenanthrolin / tetrahydrofuran / 21 h / 80 °C / Inert atmosphere; Glovebox 2: caesium carbonate / N,N-dimethyl-formamide / 120 °C / Inert atmosphere View Scheme

2,3-dimethyl-2,3-butane diol (76-09-5) + tetrahydroxydiboron (13675-18-8) + 2-chloromalonaldehyde (36437-19-1) + tert-butyl 4-hydrazino-piperidine-1-carboxylate (1196486-69-7) → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
Stage #1: 2-chloromalonaldehyde; tert-butyl 4-hydrazino-piperidine-1-carboxylate With boron trifluoride diethyl etherate In toluene Reflux; Inert atmosphere; Stage #2: tetrahydroxydiboron With 1,3-bis[(diphenylphosphino)propane]dichloronickel(II); N-ethyl-N,N-diisopropylamine; triphenylphosphine In ethanol at 80℃; for 4h; Inert atmosphere; Stage #3: 2,3-dimethyl-2,3-butane diol Inert atmosphere;	10.1 g

2,3-dimethyl-2,3-butane diol (76-09-5) + tetrahydroxydiboron (13675-18-8) + 2-Bromo-malonaldehyde (2065-75-0) + tert-butyl 4-hydrazino-piperidine-1-carboxylate (1196486-69-7) → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
Stage #1: 2-Bromo-malonaldehyde; tert-butyl 4-hydrazino-piperidine-1-carboxylate With boron trifluoride diethyl etherate In toluene Reflux; Inert atmosphere; Stage #2: tetrahydroxydiboron With 1,3-bis[(diphenylphosphino)propane]dichloronickel(II); N-ethyl-N,N-diisopropylamine; triphenylphosphine In ethanol at 20℃; for 12h; Inert atmosphere; Stage #3: 2,3-dimethyl-2,3-butane diol Inert atmosphere;	8.8 g

N-tert-butyloxycarbonylpiperidin-4-one (79099-07-3) → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydrazine hydrate / ethanol / 0.5 h / 20 °C 1.2: 2 h / 20 °C 2.1: boron trifluoride diethyl etherate / toluene / Reflux; Inert atmosphere 2.2: 12 h / 20 °C / Inert atmosphere 2.3: Inert atmosphere View Scheme

tert-butyl chloroformate (24608-52-4) → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: triethylamine 2: triethylamine; dmap / dichloromethane 3: sodium hydride / N,N-dimethyl-formamide 4: tetrahydrofuran View Scheme

2,3-dimethyl-2,3-butane diol (76-09-5) + tert-butyl 4-(4-iodo-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-73-0) → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
Stage #1: tert-butyl 4-(4-iodo-1H-pyrazol-1-yl)piperidine-1-carboxylate With isopropylmagnesium chloride In tetrahydrofuran at -25 - 20℃; for 2h; Inert atmosphere; Stage #2: With Trimethyl borate In tetrahydrofuran at 5 - 10℃; for 2.5h; Stage #3: 2,3-dimethyl-2,3-butane diol In tetrahydrofuran at 60℃; for 2.5h; Temperature; Concentration;

pyrazole-4-boronic acid pinacol ester (269410-08-4) + N-Boc-piperidine-4-yl halide → tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1)

Conditions	Yield
With potassium carbonate In acetonitrile

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) → 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine hydrochloride (1175273-62-7)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane at 35℃; for 3h;	100%
Stage #1: tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate With trifluoroacetic acid at 0 - 20℃; for 0.166667h; Stage #2: With hydrogenchloride In 1,4-dioxane	100%
With hydrogenchloride In 1,4-dioxane at 35℃; for 3h;
With hydrogenchloride In ethyl acetate at 20℃; for 2h;

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) → 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine hydrochloride

Conditions	Yield
With hydrogenchloride In 1,4-dioxane; ethyl acetate at 20℃;	100%
With hydrogenchloride In 1,4-dioxane at 20℃; for 1h;	100%
With hydrogenchloride In 1,4-dioxane at 20℃; for 16h;
With hydrogenchloride In 1,4-dioxane at 35℃; for 3h;

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + (S)-methyl 6-bromo-2-methyl-5-propoxy-3,4-dihydroquinoline-1(2H)-carboxylate → (S)-methyl 6-(1-(1-(tert-butoxycarbonyl)piperidin-4-yl)-1H-pyrazol-4-yl)-2-methyl-5-propoxy-3,4-dihydroquinoline-1(2H)-carboxylate

Conditions	Yield
With chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); caesium carbonate In 1,4-dioxane; water at 100℃; for 5h; Microwave irradiation;	100%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) → 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)-1H-pyrazol-1-yl)piperidine (1175708-03-8)

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 0 - 20℃; for 4h;	100%
With trifluoroacetic acid In dichloromethane at 20 - 40℃; for 0.25h;	100%
With trifluoroacetic acid In dichloromethane at 20℃; for 1h;

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + 6-bromo-3-chloro-4-methoxypyrazolo[1,5-a]pyridine → tert-butyl 4-(4-(3-chloro-4-methoxypyrazolo[1,5-a]pyridin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 80℃; Inert atmosphere; Sealed tube;	100%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + 3-chloro-N-(3,5-dimethoxyphenyl)quinoxalin-6-amine (1346245-13-3) → tert-butyl 4-(4-(7-((3,5-dimethoxyphenyl)amino)quinoxalin-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium acetate In 1,4-dioxane; water at 80℃; for 16h; Inert atmosphere;	99%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + (S)-2-((4-(5-bromopyrimidine-2-yl)morpholin-2-yl)methyl)-6-(3-fluorophenyl)pyridazine-3(2H)-one → (S)-tert-butyl 4-(4-(2-(2-((3-(3-fluorophenyl)-6-oxopyridazin-1(6H)-yl)methyl)morpholino)pyrimidin-5-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In tetrahydrofuran; water at 80℃; for 2h; Inert atmosphere;	98%
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In tetrahydrofuran at 80℃; for 2h; Inert atmosphere;	86 mg

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + 6-bromo-4-(6-fluoropyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile → tert-butyl 4-(4-(3-cyano-4-(6-fluoropyridin-3-yl)pyrazolo[1,5-a]pyridin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane at 80℃; Inert atmosphere; Sealed tube;	98%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + 5-bromo-3-(1-(3,5-difluorobenzyl)-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine (1450642-85-9) → tert-butyl 4-(4-(3-(1-(3,5-difluorobenzyl)-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (1562305-29-6)

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,2-dimethoxyethane; water at 20℃; for 15h;	96%

5-amino-2-bromopyrazine (59489-71-3) + tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) → tert-butyl 4-(4-(5-aminopyrazin-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane; water at 90℃; for 16h; Suzuki Coupling; Inert atmosphere; Sealed tube;	96%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + 5-bromo-2-methyl-3-nitropyridine (911434-05-4) → tert-butyl 4-[4-(6-methyl-5-nitropyridin-3-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate (1229457-95-7)

Conditions	Yield
Stage #1: 5-bromo-2-methyl-3-nitropyridine; tetrakis(triphenylphosphine) palladium(0) In 1,2-dimethoxyethane at 20℃; for 0.333333h; Stage #2: tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate With potassium carbonate In 1,2-dimethoxyethane; isopropyl alcohol at 20 - 85℃;	95%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + (R)-5-bromo-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-tert-butyloxycarbonylaminopyridine (1569895-70-0) → C31H38Cl2FN5O5 (1569895-72-2)

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In water; N,N-dimethyl-formamide at 60℃; for 6h; Inert atmosphere;	95%
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In water; N,N-dimethyl-formamide at 60℃; for 3h; Suzuki Coupling;	85%

5-bromo-3-[1 (R)-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-2-ylamine + tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) → 4-(4-{6-amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate In 1,2-dimethoxyethane; water at 90℃; for 3h; Suzuki coupling; Inert atmosphere;	94%
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In water; N,N-dimethyl-formamide for 16h; Inert atmosphere;	80%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; tetrabutylammomium bromide; caesium carbonate In water; benzene at 70℃; for 5h; Inert atmosphere;	76%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + 7-bromo-6-methylimidazo[1,2-a]pyridine → tert-butyl 4-(4-(6-methylimidazo[1,2-a]pyridin-7-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride In 1,4-dioxane; water at 50℃; for 1.5h;	93%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + 5-bromo-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-tert-butyloxycarbonylaminopyridine → tert-butyl 4-(4-(6-((tert-butoxycarbonyl)amino)-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In water; N,N-dimethyl-formamide at 60℃; for 6h; Inert atmosphere;	92.3%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + 5-bromo-1H-pyrrolo[2,3-b]pyridine (183208-35-7) → 4-(4-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylic acid tert-butyl ester (1562305-10-5)

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,2-dimethoxyethane; water at 100℃; for 2h; Suzuki-Miyaura Coupling;	92%
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,2-dimethoxyethane; water Inert atmosphere; Reflux;	71%
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,2-dimethoxyethane; water Inert atmosphere; Reflux;	71%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In 1,2-dimethoxyethane; water at 20℃; for 15h;	46.2%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,4-dioxane; water at 100℃; for 1h; Inert atmosphere;

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + 5-bromo-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-benzyloxycarbonylaminopyridine → tert-butyl 4-(4-(6-(((benzyloxy)carbonyl)amino)-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In water; N,N-dimethyl-formamide at 60℃; for 6h; Inert atmosphere;	91.8%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + C13H10BrN3O (1239369-33-5) → C26H30N6O3 (1239369-35-7)

Conditions	Yield
Stage #1: tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate; C13H10BrN3O With bis-triphenylphosphine-palladium(II) chloride In 1,4-dioxane at 20℃; for 0.5h; Suzuki coupling; Stage #2: With sodium carbonate In 1,4-dioxane; water for 3h; Suzuki coupling; Reflux;	91%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + methyl 6-((6-bromo-2-oxobenzo[d]thiazole-3(2H)-yl)methyl)nicotinate → methyl 6-((6-(1-(1-(tert-butoxycarbonyl)piperidine-4-yl)-1H-pyrazole-4-yl)-2-oxobenzo[d]thiazole-3(2H)-yl)methyl)nicotinate

Conditions	Yield
With dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); caesium carbonate In 1,4-dioxane; water at 100℃; for 18h;	90.7%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + 1-((1-(5-bromopyrimidin-2-yl)piperidin-3-yl)methyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-[1 , 2,3]triazolo[4,5-b]pyrazine → tert-butyl 4-(4-(2-(3-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)piperidin-1-yl)pyrimidin-5-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In tetrahydrofuran; water at 80℃; for 2h; Inert atmosphere;	90%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In tetrahydrofuran; water at 80℃; for 12h;	90%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + N-(3-(2-(3-amino-6-bromopyrazin-2-yl)-1H-benzo[d]imidazol-1-yl)phenyl)acetamide → tert-butyl 4-(4-(6-(1-(3-acetamidophenyl)-1H-benzo[d]imidazol-2-yl)-5-aminopyrazin-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Conditions	Yield
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate In 1,4-dioxane; water at 100℃; Suzuki Coupling; Inert atmosphere;	90%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + 3-hydroxy-5-bromo-2-nitropyridine (691872-15-8) → C18H23N5O5

Conditions	Yield
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; potassium carbonate In 1,2-dimethoxyethane; water at 90℃; for 16h; Inert atmosphere; Large scale;	90%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + (R)-5-bromo-N,N-bis-(tert-butoxycarbonyl)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridine-2-amine (877399-47-8) → C36H46Cl2FN5O7

Conditions	Yield
With 5%-palladium/activated carbon; potassium carbonate In water; toluene at 70℃; for 4h; Temperature; Reagent/catalyst; Suzuki Coupling; Inert atmosphere;	90%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + (S)-4-(2-chloro-6-(3,5-dimethylisoxazol-4-yl)quinazolin-4-yl)-3-phenylmorpholine → tert-butyl (S)-4-(4-(6-(3,5-dimethylisoxazol-4-yl)-4-(3-phenylmorpholino)quinazolin-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate In 1,4-dioxane; water at 90℃; for 1.5h; Inert atmosphere;	87%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + (5-bromo-3-(2-methoxybenzoyl)-1H-pyrrolo[2,3-b]pyridin-1-yl)methyl pivalate → tert-butyl 4-(4-(3-(2-methoxybenzoyl)-1-(pivaloyloxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,2-dimethoxyethane; water at 100℃; for 1.5h; Suzuki-Miyaura Coupling;	86%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + (R)-2-bromo-7-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)quinoxaline → tert-butyl (R)-4-(4-(7-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)quinoxalin-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; tetrabutylammomium bromide; caesium carbonate In water; toluene at 80℃; for 5h; Inert atmosphere;	86%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + (5-bromo-3-(2-chloro-4-(phenoxymethyl)benzoyl)-1H-pyrrolo[2,3-b]pyridin-1-yl)methyl pivalate → tert-butyl 4-(4-(3-(2-chloro-4-(phenoxymethyl)benzoyl)-1-((pivaloyloxy)methyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,2-dimethoxyethane; water at 100℃; for 1.5h; Suzuki-Miyaura Coupling;	85%

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (877399-74-1) + 1-[(2S)-6-bromo-5-(2-fluorophenoxy)-2-methyl-1,2,3,4-tetrahydroquinolin-1-yl]ethan-1-one → (S)-tert-butyl 4-(4-(1-acetyl-5-(2-fluorophenoxy)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate In 1,4-dioxane; water at 80℃; for 12h;	85%

Upstream product

• 269410-08-4 pyrazole-4-boronic acid pinacol ester 
• 141699-59-4 1-(tert-butoxycarbonyl)piperidin-4-yl methanesulfonate 
• 877399-50-3 4-(4-bromo-1H-pyrazol-1-yl)piperidine-1-carboxylic acid tert-butyl ester 
• 1195-66-0 2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 
• 73183-34-3 bis(pinacol)diborane 
• 185990-03-8 dimethylphenyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)silane 
• 24608-52-4 tert-butyl chloroformate 
• 180695-79-8 tert-butyl 4-bromo-1-piperidinecarboxylate 
• 76-09-5 2,3-dimethyl-2,3-butane diol 
• 877399-73-0 tert-butyl 4-(4-iodo-1H-pyrazol-1-yl)piperidine-1-carboxylate 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 13675-18-8 tetrahydroxydiboron 
• 2065-75-0 2-Bromo-malonaldehyde 
• 1196486-69-7 tert-butyl 4-hydrazino-piperidine-1-carboxylate 

Downstream Products

• 949559-56-2 tert-butyl 4-(4-(4-(4-amino-2-fluorophenoxy)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate 
• 1175273-62-7 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine hydrochloride 
• 1126403-30-2 tert-butyl 4-{4-[2-(3-hydroxymethylphenyl)pyrimidin-5-yl]-pyrazol-1-yl}piperidine-1-carboxylate 
• 1323919-64-7 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine 
• 1323919-58-9 4-(4-{5-[2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridin-4-yl]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester 
• 877399-52-5 crizotinib 
• 1562305-09-2 tert-butyl 4-(4-(3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-1-yl) piperidine-1-carboxylate 

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