571188-59-5

Basic information

• Product Name: OTAVA-BB 1207229
• Synonyms: 1-BOC-4-(6-AMINOPYRIDIN-3-YL)PIPERAZINE;OTAVA-BB 1207229;4-(6-Aminopyridin-3-yl)piperazine-1-carboxylic acid tert-butyl ester;1-Piperazinecarboxylic acid, 4-(6-aMino-3-pyridinyl)-, 1,1-diMethylethyl ester;tert-butyl 4-(6-aMinopyri;4-(6-aMinopyridin-3-yl)piperazine-1-carboxylic;4-(6-AMinopyridin-3-yl)-1-Boc-piperazine;tert-butyl 4-(6-amino-3-pyridyl)piperazine-1-carboxylate
• CAS NO: 571188-59-5
• Molecular Formula: C₁₄H₂₂N₄O₂
• Molecular Weight: 278.35008
• EINECS: 1592732-453-0
• Product Categories: PD 0332991;Palbociclib;Anticancer
• Mol File: 571188-59-5.mol
• Article Data: 76

Chemical Properties

• Melting Point: 130-132℃
• Boiling Point: 454.066°C at 760 mmHg
• Flash Point: 228.411°C
• Appearance: /
• Density: 1.182
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.569
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• Solubility: DMSO (Slightly), Methanol (Very Slightly)
• PKA: 7.36±0.26(Predicted)
• Sensitive: Air Sensitive
• CAS DataBase Reference: OTAVA-BB 1207229(CAS DataBase Reference)
• NIST Chemistry Reference: OTAVA-BB 1207229(571188-59-5)
• EPA Substance Registry System: OTAVA-BB 1207229(571188-59-5)

Safety Data

• Hazardous Substances Data: 571188-59-5(Hazardous Substances Data)

Usage

Physical Form

Solid

Uses

4-(6-Amino-3-pyridyl)-1-Boc-piperazine is used as an organic chemical synthesis intermediate.

InChI:InChI=1/C14H22N4O2/c1-14(2,3)20-13(19)18-8-6-17(7-9-18)11-4-5-12(15)16-10-11/h4-5,10H,6-9H2,1-3H3,(H2,15,16)

Synthetic route

4-(6-nitropyridin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (571189-16-7) → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethanol; water for 2h;	100%
With palladium on activated charcoal; hydrogen In ethanol for 3h;	100%
With palladium 10% on activated carbon; hydrogen In methanol at 25℃; under 2250.23 Torr; for 4h; Autoclave;	99.1%

1-(5-nitro-2Z,4Z-pentadienenitrile-4-yl)-4-tert-butoxycarbonylpiperazine → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
With 5%-palladium/activated carbon; hydrogen; ammonium chloride In methanol at 40 - 45℃; under 1500.15 - 2250.23 Torr; Temperature; Reagent/catalyst; Pressure; Solvent; Autoclave;	95.3%

2-aminopyridine (504-29-0) + 1-t-Butoxycarbonylpiperazine (57260-71-6) → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; oxygen In 1,2-dichloro-ethane for 10h; Reagent/catalyst; Irradiation;	95%

di-tert-butyl dicarbonate (24424-99-5) + 5-(piperazin-1-yl)pyridin-2-amine → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
In methanol; water at 20℃; Solvent; Inert atmosphere;	94%

2-amino-5-iodopyridine (20511-12-0) + 1-t-Butoxycarbonylpiperazine (57260-71-6) → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
With potassium phosphate; copper(l) iodide; ethylene glycol In isopropyl alcohol at 110℃; for 10h; Ullmann Condensation; Sealed tube;	85%

1-(6-nitropyridin-3-yl)piperazine (775288-71-6) → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 190.93 g / aq. NaHCO3 / tetrahydrofuran / 3 h 2: 83 percent / H2 / Raney Nickel / methanol / 5 h / 2585.74 Torr View Scheme
Multi-step reaction with 2 steps 1: triethylamine / tetrahydrofuran / 50 °C 2: 10% palladium on activated carbon; hydrogen / methanol View Scheme
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / water; tetrahydrofuran / 3 h / 20 °C 2: hydrogen / water; methanol / 5 h / 2585.81 Torr View Scheme
Multi-step reaction with 2 steps 1: dmap; triethylamine / dichloromethane / 8 h / 20 °C 2: hydrogen; palladium 10% on activated carbon / methanol / 20 °C View Scheme

5-bromo2-nitropyridine (39856-50-3) → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: tetra-n-butylammonium iodide; K2CO3 / dimethylsulfoxide / 80 - 100 °C 2: 190.93 g / aq. NaHCO3 / tetrahydrofuran / 3 h 3: 83 percent / H2 / Raney Nickel / methanol / 5 h / 2585.74 Torr View Scheme
Multi-step reaction with 3 steps 1: tetra-(n-butyl)ammonium iodide; potassium carbonate / dimethyl sulfoxide / 80 °C 2: triethylamine / tetrahydrofuran / 50 °C 3: 10% palladium on activated carbon; hydrogen / methanol View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / dimethyl sulfoxide / 65 °C 2: hydrogen / palladium 10% on activated carbon / ethanol / 16 h / 20 °C / Inert atmosphere View Scheme

4-(6-nitropyridin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (571189-16-7) + aluminum nickel → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
In methanol; n-heptane; water; hydrogen

1-t-Butoxycarbonylpiperazine (57260-71-6) → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / dimethyl sulfoxide / 65 °C 2: hydrogen / palladium 10% on activated carbon / ethanol / 16 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / dimethyl sulfoxide / 65 °C 2: palladium 10% on activated carbon; hydrogen / ethanol / 16 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: 1-methyl-pyrrolidin-2-one / 3 h / 120 °C 2: hydrogen; palladium 10% on activated carbon / ethanol / 2 h View Scheme

di-tert-butyl dicarbonate (24424-99-5) → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / water; tetrahydrofuran / 1.5 h / 5 - 28 °C / Inert atmosphere 2: hydrogen / palladium 10% on activated carbon / water; methanol / 0.25 h / 19 - 54 °C / 1551.49 - 2327.23 Torr / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide 2: hydrogen; palladium 10% on activated carbon / methanol View Scheme
Multi-step reaction with 2 steps 1.1: N,N-dimethyl-formamide; isopropyl alcohol / 20 - 60 °C 1.2: 20 °C 2.1: zinc; acetic acid / water / 2 h / 10 - 20 °C View Scheme

2-amino-5-fluoropyridine (21717-96-4) → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: sulfuric acid; dihydrogen peroxide / water / 16 h / 0 - 20 °C 2: triethylamine / toluene / 16 h / 100 °C 3: hydrogen / Raney-Nickel / methanol / 4 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: copper(l) iodide; potassium carbonate; ethyl 2-oxocyclohexane carboxylate / N,N-dimethyl-formamide / 130 °C / Inert atmosphere 2: methanol; water / 20 °C / Inert atmosphere View Scheme

5-fluoro-2-nitro-pyridine (779345-37-8) → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / toluene / 16 h / 100 °C 2: hydrogen / Raney-Nickel / methanol / 4 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / ethanol / 36 h / 60 °C 2: acetic acid; palladium on activated charcoal; hydrogen / methanol / 4 h / 25 °C View Scheme
Multi-step reaction with 2 steps 1.1: potassium carbonate / dimethyl sulfoxide / 0.5 h / 20 °C 1.2: 5 h / 70 °C 2.1: FeO(OH)/C; hydrazine hydrate / ethanol / Reflux View Scheme

5-chloro-2-nitropyridine (52092-47-4) → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / dimethyl sulfoxide / 100 - 110 °C / Microwave irradiation 2: palladium 10% on activated carbon; hydrogen / methanol / 4 h / 20 °C View Scheme

4-(6-nitropyridin-3-yl)piperazin-1-ium bromide → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine; dmap / dichloromethane / 8 h / 20 °C 2: palladium 10% on activated carbon; hydrogen / methanol / 20 °C View Scheme

5-bromo-2-pyridylamine (1072-97-5) + 1-t-Butoxycarbonylpiperazine (57260-71-6) → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
With potassium phosphate; copper(l) iodide; ethylene glycol In isopropyl alcohol at 110℃; for 24h; Ullmann Condensation; Sealed tube;

5-bromo2-nitropyridine (39856-50-3) + 1-t-Butoxycarbonylpiperazine (57260-71-6) → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine; lithium chloride / dimethyl sulfoxide / 12 h / 60 - 65 °C 2: hydrogen / methanol / 4 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 50 °C 2: hydrogen; palladium on activated charcoal / methanol / 20 °C View Scheme
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / ethanol / 20 h / 25 °C / Inert atmosphere 2: hydrogen; palladium on activated charcoal / ethanol / 3 h / 25 °C View Scheme
Multi-step reaction with 2 steps 1: triethylamine / dimethyl sulfoxide / 18 h / 60 °C 2: iron; ammonium chloride / ethanol / 6 h / 70 °C View Scheme

piperazine (110-85-0) + 5-chloro-2-pyridylamine (1072-98-6) + di-tert-butyl dicarbonate (24424-99-5) → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
Stage #1: piperazine; di-tert-butyl dicarbonate In dichloromethane at 0 - 20℃; for 2h; Stage #2: 5-chloro-2-pyridylamine In water; N,N-dimethyl-formamide at 100℃; for 8h;
Stage #1: piperazine; di-tert-butyl dicarbonate In dichloromethane at 0 - 20℃; for 2h; Stage #2: 5-chloro-2-pyridylamine In water; N,N-dimethyl-formamide at 100℃; for 8h;
Stage #1: piperazine; di-tert-butyl dicarbonate In dichloromethane at 0 - 20℃; for 2h; Stage #2: 5-chloro-2-pyridylamine In water; N,N-dimethyl-formamide at 100℃; for 8h;
Stage #1: piperazine; di-tert-butyl dicarbonate In dichloromethane at 0 - 20℃; for 2h; Stage #2: 5-chloro-2-pyridylamine In water; N,N-dimethyl-formamide at 100℃; for 8h;

5-bromo-2-pyridylamine (1072-97-5) → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: dihydrogen peroxide; sulfuric acid / water / 5 - 15 °C 2: lithium chloride; triethylamine / acetonitrile / 32 h / 70 - 73 °C / Inert atmosphere 3: palladium 10% on activated carbon; hydrogen / methanol / 12 h / 20 °C / 2250.23 Torr View Scheme

5-fluoro-2-nitro-pyridine (779345-37-8) + 1-t-Butoxycarbonylpiperazine (57260-71-6) → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium carbonate / tetrahydrofuran / 1 h / 20 °C 1.2: 8 h / 50 °C 2.1: palladium 10% on activated carbon / methanol / 10 h / 20 °C View Scheme

5-bromo2-nitropyridine (39856-50-3) + di-tert-butyl dicarbonate (24424-99-5) → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: tetra-(n-butyl)ammonium iodide; potassium carbonate / dimethyl sulfoxide / 80 °C 1.2: 3 h / 20 °C 2.1: hydrogen / water; methanol / 2585.81 Torr View Scheme

C5H5N3O2 → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide / 5 h / 20 - 85 °C 2: 5%-palladium/activated carbon; ammonium chloride; hydrogen / methanol / 40 - 45 °C / 1500.15 - 2250.23 Torr / Autoclave View Scheme

2-amino-5-iodopyridine (20511-12-0) → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: CVT-2537; sodium carbonate; copper(l) iodide / N,N-dimethyl-formamide / 98 °C / Inert atmosphere 2: methanol; water / 20 °C / Inert atmosphere View Scheme

5-chloro-2-pyridylamine (1072-98-6) → tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: copper(l) iodide; rac-Pro-OH; potassium carbonate / butan-1-ol / 120 °C / Inert atmosphere 2: methanol; water / 20 °C / Inert atmosphere View Scheme

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + 2-chloroethanal (107-20-0) → tert-butyl 4-(imidazo[1,2-a]pyridin-6-yl)piperazine-1-carboxylate (684223-68-5)

Conditions	Yield
In ethanol; water for 15h; Heating;	100%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + C15H17ClN2OS → tert-butyl 4-(6-((3-cyclopentyl-2-(dimethylcarbamoyl)thieno[2,3-c]pyridin-5-yl)amino)pyridin-3-yl)piperazine-1-carboxylate

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In 1,4-dioxane for 12h; Inert atmosphere; Reflux;	100%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + C26H35ClN4O3Si → C40H56N8O5Si

Conditions	Yield
With palladium diacetate; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In 1,4-dioxane at 100℃; for 1.5h;	100%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + 2-chloro-5-methyl-6-bromo-8-cyclopentylpyridine[2,3-d]pyrimidin-8-hydro-7-one → tert‑butyl 4‑(6‑((6‑bromo‑8‑cyclopentyl‑5‑methyl‑7‑oxo‑7,8‑dihydropyrido[2,3‑d]pyrimidin‑2‑yl)amino)pyridin‑3‑yl)piperazine‑1‑carboxylate (571188-82-4)

Conditions	Yield
Stage #1: tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate With isopropyl chloride In tetrahydrofuran at 20℃; for 1h; Inert atmosphere; Large scale; Stage #2: 2-chloro-5-methyl-6-bromo-8-cyclopentylpyridine[2,3-d]pyrimidin-8-hydro-7-one With isopropylmagnesium chloride In tetrahydrofuran at 70℃; Temperature; Large scale;	99.9%
With isopropylmagnesium chloride In tetrahydrofuran at 20 - 60℃; Inert atmosphere;	93%
With lithium hexamethyldisilazane In tetrahydrofuran; N,N-dimethyl-formamide at 0 - 25℃;	92%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) → 5-piperazin-1-ylpyridin-2-ylamine dihydrochloride

Conditions	Yield
With hydrogenchloride In 1,4-dioxane; dichloromethane at 20℃; for 16h;	99%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + 1-(2-chloro-8-cyclopentyl-5-methyl-7-oxo-1,3,8-triaza-8H-naphth-6-yl)-1-ethanone → 4-[6-(6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)pyridine-3-yl]piperazine-1-carboxylic acid tert-butyl ester

Conditions	Yield
Stage #1: tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate With lithium hexamethyldisilazane In tetrahydrofuran at 10 - 20℃; for 1h; Inert atmosphere; Stage #2: 1-(2-chloro-8-cyclopentyl-5-methyl-7-oxo-1,3,8-triaza-8H-naphth-6-yl)-1-ethanone In tetrahydrofuran at 20℃; for 15h; Inert atmosphere;	93.7%
With lithium hexamethyldisilazane In N,N-dimethyl-formamide at 0 - 25℃;	79%
With potassium carbonate In N,N-dimethyl-formamide at 80 - 85℃; for 4h;	70%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (1211443-61-6) → N,N‐dimethyl‐7‐cyclopentyl‐2‐{[5‐(4-tert-butoxycarbonylpiperazin‐1‐yl)pyridin‐2‐yl]amino}‐7H‐pyrrolo[2,3‐d]pyrimidine‐6‐carboxamide (1374639-78-7)

Conditions	Yield
With palladium diacetate; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl at 90 - 100℃; for 3h; Inert atmosphere;	92.2%
Stage #1: 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide With potassium carbonate In dichloromethane at 60℃; for 0.5h; Stage #2: tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate In dichloromethane at 60℃; for 1h; Reagent/catalyst; Temperature;	86%
Stage #1: tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate With lithium hexamethyldisilazane In tetrahydrofuran; toluene at -5 - 35℃; Inert atmosphere; Stage #2: 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide In tetrahydrofuran; toluene at -5 - 35℃;	86.6%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + C17H20ClN3O3 → C31H41N7O5

Conditions	Yield
Stage #1: tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate With lithium hexamethyldisilazane In tetrahydrofuran; toluene at 20℃; for 0.5h; Inert atmosphere; Stage #2: C17H20ClN3O3 In tetrahydrofuran; toluene at 20℃; for 1h; Inert atmosphere;	92%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + N-formylbenzotriazole (72773-04-7) → tert-butyl 4-(6-formamidopyridin-3-yl)piperazine-1-carboxylate

Conditions	Yield
In tetrahydrofuran Heating / reflux;	91.2%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + 7-chloro-1-cyclopentyl-3-(1-ethoxyvinyl)-4,8-dimethyl-1,6-naphthyridin-2(1H)-one → 4-(6-((1-cyclopentyl-3-(1-ethoxyvinyl)-4,8-dimethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-7-yl)amino)pyridin-3-yl)piperazine-1-carboxylic acid tert-butyl ester

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In toluene Inert atmosphere; Reflux;	90.8%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + mercaptoacetic acid (68-11-1) + tert-butyl 4-(hydroxymethyl)piperidin-1-carboxylate (123855-51-6) → tert-butyl 4-(6-(2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-oxothiazolidin-3-yl)pyridin-3-yl)piperazine-1-carboxylate (1402049-32-4)

Conditions	Yield
Stage #1: tert-butyl 4-(hydroxymethyl)piperidin-1-carboxylate With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide In dimethyl sulfoxide; ethyl acetate at 0 - 25℃; Inert atmosphere; Stage #2: tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate; mercaptoacetic acid In dimethyl sulfoxide; ethyl acetate at 25℃; Inert atmosphere;	90%
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide In dimethyl sulfoxide; ethyl acetate at 0 - 20℃;

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + tert-butyl 7-benzyl-2-(methylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate → tert-butyl 7-benzyl-2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate

Conditions	Yield
Stage #1: tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate With sodium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: tert-butyl 7-benzyl-2-(methylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate In tetrahydrofuran at -70℃; for 0.5h; Inert atmosphere;	89.1%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + 2-methoxy-4-(hydroxymethyl)-3-methoxybenzoate (79236-96-7) + mercaptoacetic acid (68-11-1) → tert-butyl 4-(6-(2-(2-methoxy-4-(methoxycarbonyl)phenyl)-4-oxothiazolidin-3-yl)pyridin-3-yl)piperazine-1-carboxylate (1402049-25-5)

Conditions	Yield
Stage #1: 2-methoxy-4-(hydroxymethyl)-3-methoxybenzoate With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide In dimethyl sulfoxide; ethyl acetate at 0 - 25℃; Inert atmosphere; Stage #2: tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate; mercaptoacetic acid In dimethyl sulfoxide; ethyl acetate at 25℃; Inert atmosphere;	89%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + 5-(2-chloro-5-fluoropyrimidin-4-yl)-2-methyl-3-isopropenyl-2H-indazole → tert-butyl 4-[6-({5-fluoro-4-[2-methyl-3-(prop-1-en-2-yl)-2H-indazol-5-yl]pyrimidin-2-yl}amino)pyridin-3-yl]piperazine-1-carboxylate

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In 1,4-dioxane at 110℃; for 16h; Inert atmosphere;	88.94%
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In 1,4-dioxane at 110℃; for 16h; Inert atmosphere;	88.94%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + C16H18ClN3O3 → 8-cyclopentyl-2-[[5-[4-[(1,1-dimethylethoxy)carbonyl]-1-piperazinyl]-2-pyridinyl]amino]-7,8-dihydro-5-methyl-7-oxo-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (571189-03-2)

Conditions	Yield
With lithium hexamethyldisilazane In toluene at -10 - 0℃; for 0.5h;	88.2%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + Ethoxycarbonyl isothiocyanate (16182-04-0) → tert-butyl 4-(6-{[(ethoxycarbonyl)carbamothioyl]amino}pyridin-3-yl)piperazine-1-carboxylate

Conditions	Yield
In 1,4-dioxane at 20℃; for 3h;	88%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + 2-chloro-8-cyclopentyl-6-iodo-5-methylpyrido[2,3-d]pyrimidin-7(8H)-one → tert-butyl 4-(6-(8-cyclopentyl-6-iodo-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)pyridin-3-yl)piperazine-1-carboxylate (571189-22-5)

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran; N,N-dimethyl-formamide at 0 - 25℃;	87%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + 1-(2-chloro-8-cyclopentyl-5-methyl-7-oxo-1,3,8-triaza-8H-naphth-6-yl)-1-ethanone → PD 0332991 (571190-30-2)

Conditions	Yield
Stage #1: tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate With lithium hexamethyldisilazane In tetrahydrofuran; tert-butyl methyl ether for 0.5h; Stage #2: 1-(2-chloro-8-cyclopentyl-5-methyl-7-oxo-1,3,8-triaza-8H-naphth-6-yl)-1-ethanone In tetrahydrofuran; tert-butyl methyl ether at 20℃; for 1h; Solvent; Reagent/catalyst;	86.6%
Stage #1: tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate; 1-(2-chloro-8-cyclopentyl-5-methyl-7-oxo-1,3,8-triaza-8H-naphth-6-yl)-1-ethanone With lithium hexamethyldisilazane In toluene at 50 - 55℃; Inert atmosphere; Stage #2: With hydrogenchloride In dichloromethane; water at 20℃; for 12h; Inert atmosphere;	82.6%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + 2-methylisothiourea sulphate (14527-26-5, 867-44-7) → N-(5-(4-N-tert-butoxycarbonyl-1-N-hexahydro-pyrazinyl)2-pyridyl)guanidine sulphate

Conditions	Yield
In water at 20 - 25℃; for 6h;	86.5%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + C14H17FN4O → N,N‐dimethyl‐7‐cyclopentyl‐2‐{[5‐(4-tert-butoxycarbonylpiperazin‐1‐yl)pyridin‐2‐yl]amino}‐7H‐pyrrolo[2,3‐d]pyrimidine‐6‐carboxamide (1374639-78-7)

Conditions	Yield
Stage #1: tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate With lithium hexamethyldisilazane In tetrahydrofuran; toluene at 0 - 10℃; for 1h; Stage #2: C14H17FN4O In tetrahydrofuran; toluene at 0 - 20℃; for 2.5h;	86%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + 5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) → tert-butyl 4-(6-{[5-bromo-4-(cyclopentylamino)pyrimidin-2-yl]amino}pyridin-3-yl)piperazine-1-carboxylate (733038-80-7)

Conditions	Yield
Stage #1: 5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine With potassium carbonate In dichloromethane at 60℃; for 0.5h; Stage #2: tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate In dichloromethane at 20 - 60℃; for 1h;	85%
Stage #1: tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate; 5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine In xylene; butan-1-ol at 100 - 140℃; Stage #2: With sodium hydroxide In water; ethyl acetate; xylene; butan-1-ol

6-acetyl-8-cyclopentyl-5-methyl-2-(methylsulfinyl)pyrido[2,3-d]pyrimidin-7(8H)-one (850628-86-3) + tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) → PD 0332991 (571190-30-2)

Conditions	Yield
Stage #1: 6-acetyl-8-cyclopentyl-5-methyl-2-(methylsulfinyl)pyrido[2,3-d]pyrimidin-7(8H)-one; tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate With lithium hexamethyldisilazane In toluene at 70 - 75℃; Inert atmosphere; Stage #2: With hydrogenchloride In dichloromethane; water at 20℃; for 12h; Inert atmosphere;	85%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + tert-butyl 7-bromo-4-chloro-1-oxoisoindoline-2-carboxylate → tert-butyl 4-chloro-7-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)-1-oxoisoindoline-2-carboxylate

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 110℃; for 6h; Inert atmosphere;	79%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + 6-chloro-8-bromoimidazo[1,2-a]pyridine (957187-27-8) → tert-butyl 4-(6-(6-chloroimidazo[1,2-a]pyridin-8-ylamino)pyridine-3-yl)piperazine-1-carboxylate (1433821-24-9)

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In 1,4-dioxane at 100℃; for 5h; Inert atmosphere;	78%

tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) + 6-(2-chloro-5-fluoropyrimidin-4-yl)-1-isopropyl-4-methoxy-2-methylimidazo[4,5-c]pyridine → tert-butyl 4-[6-[[5-fluoro-4-(1-isopropyl-4-methoxy-2-methylimidazo[4,5-c]pyridin-6-yl)pyrimidin-2-yl]amino]-3-pyridyl]piperazine-1-carboxylate

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In 1,4-dioxane at 110℃; for 16h;	76%

Upstream product

• 571189-16-7 4-(6-nitropyridin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester 
• 20511-12-0 2-amino-5-iodopyridine 
• 57260-71-6 1-t-Butoxycarbonylpiperazine 
• 1072-97-5 5-bromo-2-pyridylamine 
• 39856-50-3 5-bromo2-nitropyridine 
• 504-29-0 2-aminopyridine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 110-85-0 piperazine 
• 1072-98-6 5-chloro-2-pyridylamine 
• 52092-47-4 5-chloro-2-nitropyridine 
• 779345-37-8 5-fluoro-2-nitro-pyridine 
• 21717-96-4 2-amino-5-fluoropyridine 
• 775288-71-6 1-(6-nitropyridin-3-yl)piperazine 

Downstream Products

• 571189-41-8 4-[6-(8-cyclopropyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)pyridin-3-yl]piperazine-1-carboxylic acid tert-butyl ester 
• 571189-39-4 4-[6-(8-cyclohexyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)pyridin-3-yl]piperazine-1-carboxylic acid tert-butyl ester 
• 571188-82-4 tert?butyl 4?(6?((6?bromo?8?cyclopentyl?5?methyl?7?oxo?7,8?dihydropyrido[2,3?d]pyrimidin?2?yl)amino)pyridin?3?yl)piperazine?1?carboxylate 
• 571188-92-6 4-[6-[[8-cyclopentyl-7,8-dihydro-7-oxo-6-(phenylmethyl)pyrido[2,3-d]pyrimidin-2-yl]amino]-3-pyridinyl]-1-piperazinecarboxylic acid 1,1-dimethylethyl ester 
• 571189-65-6 4-[6-(8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)pyridin-3-yl]piperazine-1-carboxylic acid tert-butyl ester 
• 1243244-51-0 tert-butyl 4-(6-(2-(4-(2-methylpyridin-4-yl)phenyl)acetamido)pyridin-3-yl)piperazine-1-carboxylate 
• 1374639-75-4 7-cyclopentyl-N,N-dimethyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide succinate 
• 1374639-78-7 N,N‐dimethyl‐7‐cyclopentyl‐2‐{[5‐(4-tert-butoxycarbonylpiperazin‐1‐yl)pyridin‐2‐yl]amino}‐7H‐pyrrolo[2,3‐d]pyrimidine‐6‐carboxamide 
• 571190-30-2 PD 0332991 
• 866084-31-3 tert?butyl 4?(6?((6?(1?butoxyvinyl)?8?cyclopentyl?5?methyl?7?oxo?7,8?dihydropyrido[2,3?d]pyrimidin?2?yl)amino)pyridin?3?yl)piperazine?1?carboxylate 
• 827022-33-3 6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one isethionate 
• 827022-32-2 6-acetyl-8-cyclopentyl-5-methyl-2-{[5-(piperazin-1-yl)pyridin-2yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one hydrochloride 

Relevant articles and documents

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