733039-20-8

Basic information

• Product Name: 5-broMo-2-chloro-N-cyclopentylpyriMidin-4-aMine
• Synonyms: 5-broMo-2-chloro-N-cyclopentylpyriMidin-4-aMine;4-PyriMidinaMine, 5-broMo-2-chloro-N-cyclopentyl-;5-Bromo-2-chloro-4-(cyclopentylamino)pyrimidine;N-(5-Bromo-2-chloropyrimidin-4-yl)(cyclopentyl)amine;(5-Bromo-2-chloro-pyrimidin-4-yl)-cyclopentyl-amine
• CAS NO: 733039-20-8
• Molecular Formula: C9H11BrClN3
• Molecular Weight: 276.56074
• EINECS: 200-258-5
• Product Categories: Anticancer
• Mol File: 733039-20-8.mol
• Article Data: 31

Chemical Properties

• Boiling Point: 424°C at 760 mmHg
• Flash Point: 210.2°C
• Appearance: /
• Density: 1.643g/cm³
• Vapor Pressure: 2.14E-07mmHg at 25°C
• Refractive Index: 1.645
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: 1.22±0.10(Predicted)
• CAS DataBase Reference: 5-broMo-2-chloro-N-cyclopentylpyriMidin-4-aMine(CAS DataBase Reference)
• NIST Chemistry Reference: 5-broMo-2-chloro-N-cyclopentylpyriMidin-4-aMine(733039-20-8)
• EPA Substance Registry System: 5-broMo-2-chloro-N-cyclopentylpyriMidin-4-aMine(733039-20-8)

Safety Data

• Hazard Codes: T
• Statements: 25
• Safety Statements: 45
• Hazardous Substances Data: 733039-20-8(Hazardous Substances Data)

Usage

Uses

5-Bromo-2-chloro-N-cyclopentyl-4-pyrimidinamine is an intermediate in the preparation of 2-aminopyridines as cdk4 inhibitors for treating cell proliferative disorders.

InChI:InChI=1/C9H11BrClN3/c10-7-5-12-9(11)14-8(7)13-6-3-1-2-4-6/h5-6H,1-4H2,(H,12,13,14)

Synthetic route

+ Cyclopentamine → 5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8)

Conditions	Yield
In 1,4-dioxane at 20℃; for 6h;	100%
With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 20℃; for 6h; Inert atmosphere;	100%
With sodium hydrogencarbonate In dichloromethane at 20℃; for 13h; Reagent/catalyst; Solvent;	97.5%

cyclopentyl chloride (930-28-9) + 4-amino-5-bromo-2-chloropyrimidine (205672-25-9) → 5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8)

Conditions	Yield
With triethylamine In methanol at 20℃;	92.74%
With copper diacetate; sodium hydroxide In dichloromethane at 80℃; for 10h;	77%

Cyclopentyl bromide (137-43-9) + 4-amino-5-bromo-2-chloropyrimidine (205672-25-9) → 5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8)

Conditions	Yield
With copper(II) trifluoroacetate; sodium hydroxide In 1,4-dioxane at 80℃; for 6h; Reagent/catalyst; Solvent; Temperature;	90%

2,4-dichloro-5-bromopyrimidine (36082-50-5) + Cyclopentamine (1003-03-8) → 5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + 5-bromo-4-chloro-N-cyclopentyl-2-pyrimidinamine

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0) In 1,4-dioxane at 20℃; Reagent/catalyst;

2-butenoic acid (3724-65-0) + 5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) → 2-chloro-5-methyl-8-cyclopentylpyridin[2,3-d]pyrimidin-8-hydro-7-one (1013916-37-4)

Conditions	Yield
With triethylamine; palladium dichloride In 1-methyl-pyrrolidin-2-one at 20 - 75℃; for 6h; Temperature; Solvent; Reagent/catalyst; Inert atmosphere;	94.8%
Stage #1: 5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine With triethylamine; palladium dichloride In tetrahydrofuran at 60℃; for 5h; Stage #2: 2-butenoic acid In tetrahydrofuran for 2h; Temperature; Reagent/catalyst; Solvent;	89.08%
Stage #1: 2-butenoic acid; 5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine With bis(benzonitrile)palladium(II) dichloride; N-ethyl-N,N-diisopropylamine; tris-(o-tolyl)phosphine In tetrahydrofuran at 75℃; for 20h; Heck Reaction; Inert atmosphere; Stage #2: In acetic anhydride at 75℃; for 2h; Temperature; Reagent/catalyst; Solvent;	80%
With triethylamine; palladium dichloride In 1-methyl-pyrrolidin-2-one at 75℃; for 6h; Temperature; Inert atmosphere;

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

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + prop-1-yne (74-99-7) → 2-chloro-4-cyclopentylamino-5-(propynyl)pyrimidine

Conditions	Yield
With triphenylphosphine; palladium dichloride In N,N-dimethyl-formamide at 50℃; for 20h; Reagent/catalyst; Solvent; Temperature;	85%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + methyl iodide (74-88-4) → (5-bromo-2-chloropyrimidin-4-yl)cyclopentylmethylamine

Conditions	Yield
With sodium hydride In tetrahydrofuran for 1.5h;	84%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + (E)-but-2-enoic acid (107-93-7) → 2-chloro-5-methyl-8-cyclopentylpyridin[2,3-d]pyrimidin-8-hydro-7-one (1013916-37-4)

Conditions	Yield
Stage #1: 5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine; (E)-but-2-enoic acid With palladium diacetate; triethylamine In 1-methyl-pyrrolidin-2-one at 65℃; Inert atmosphere; Stage #2: With acetic anhydride In 1-methyl-pyrrolidin-2-one at 65℃; Inert atmosphere;	81%
Stage #1: 5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine; (E)-but-2-enoic acid With N-ethyl-N,N-diisopropylamine; palladium(II) chloride benzonitrile complex; tris-(o-tolyl)phosphine In tetrahydrofuran at 70℃; for 16h; Stage #2: With acetic anhydride In tetrahydrofuran for 1.5h;	68%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + propargyl alcohol (107-19-7) → 3-(2-chloro-4-(cyclopentylamino)pyrimidin-5-yl)prop-2-yn-1-ol (1374639-76-5)

Conditions	Yield
Stage #1: 5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine With copper(l) iodide; palladium on activated charcoal; N-ethyl-N,N-diisopropylamine; bis[2-(diphenylphosphino)phenyl] ether In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Stage #2: propargyl alcohol In tetrahydrofuran for 5.5h; Reflux; Stage #3: With bis[2-(diphenylphosphino)phenyl] ether for 4h; Reflux;	74.5%
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; N-butylamine In tetrahydrofuran at 29℃; for 20h; Sonogashira Cross-Coupling; Inert atmosphere; Reflux;	62%
Stage #1: 5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine; propargyl alcohol With tetrabutyl ammonium fluoride; bis-triphenylphosphine-palladium(II) chloride In tetrahydrofuran; water at 25 - 67℃; for 2h; Inert atmosphere; Stage #2: With sodium hydrogencarbonate In ethyl acetate	47.4%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 2-chloro-4-cyclopentylaminopyrimidine-5-aldehyde

Conditions	Yield
Stage #1: 5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine With isopropylmagnesium chloride In tetrahydrofuran at 0 - 5℃; Inert atmosphere; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran at 20℃; Inert atmosphere;	74%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + acrylic acid (79-10-7) → C12H14ClN3O2

Conditions	Yield
With copper(l) iodide; N-ethyl-N,N-diisopropylamine; triphenylphosphine; nickel dichloride In ethanol at 65℃; for 8h; Inert atmosphere;	73.1%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + propynoic acid ethyl ester (623-47-2) → C14H16ClN3O2

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane; bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide In acetonitrile at 0 - 60℃; Inert atmosphere;	73%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + N,N-dimethylpropynamide (2682-34-0) → 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (1211443-61-6)

Conditions	Yield
With N,N'-Diphenyloxamid; potassium carbonate; copper(l) chloride In dimethyl sulfoxide at 90 - 100℃; for 12h; Reagent/catalyst;	73%
With N,N,N,N,-tetramethylethylenediamine; potassium carbonate; copper(l) chloride In dimethyl sulfoxide at 90 - 100℃; for 12h; Reagent/catalyst;	71%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + sodium thiomethoxide (5188-07-8) → 5‑bromo‑N‑cyclopentyl‑2‑(methylthio)pyrimidin‑4‑amine (733039-23-1)

Conditions	Yield
In dimethyl sulfoxide	72%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + (2-tert-butoxy-2-oxoethyl)zinc(II) bromide (51656-70-3) → tert-butyl 2-(2-chloro-4-(cyclopentylamino)pyrimidin-5-yl)acetate

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); monophosphine 1,2,3,4,5-pentaphenyl-1'-(di-tert-butylphosphino)ferrocene In tetrahydrofuran; 1,4-dioxane at 20℃; for 1h; Inert atmosphere;	67%
With tris-(dibenzylideneacetone)dipalladium(0); monophosphine 1,2,3,4,5-pentaphenyl-1'-(di-tert-butylphosphino)ferrocene In tetrahydrofuran; 1,4-dioxane at 20℃; for 1h; Inert atmosphere;	67%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) → 5-bromo-N4-cyclopentylpyrimidine-2,4-diamine (1169698-46-7)

Conditions	Yield
With ammonia In water; isopropyl alcohol at 120℃; for 22h;	66%
With ammonium hydroxide In isopropyl alcohol at 120℃; for 22h; Sealed tube; Inert atmosphere;	66%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + hydroxy-1-propyne (6175-54-8) → 3-(2-chloro-4-(cyclopentylamino)pyrimidin-5-yl)prop-2-yn-1-ol (1374639-76-5)

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; tetrabutyl ammonium fluoride In tetrahydrofuran at 70℃; for 5h;	65.9%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + 4-amino-N-(1-methylpiperidin-4-yl)benzamide (50534-11-7) → C22H29BrN6O

Conditions	Yield
With hydrogenchloride In water; isopropyl alcohol at 80℃; for 18h;	63%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + Propiolaldehyde diethyl acetal (10160-87-9) → [2-chloro-5-(3,3-diethoxy-prop-1-ynyl)-pyrimidin-4-yl]-cyclopentyl amine (1211442-87-3)

Conditions	Yield
Stage #1: 5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine; Propiolaldehyde diethyl acetal With triethylamine; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Stage #2: copper(l) iodide In tetrahydrofuran at 60℃; for 48h; Product distribution / selectivity; Inert atmosphere;	54%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; Sonogashira coupling;	41%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + trimethylsilylacetylene (1066-54-2) → 2-chloro-N-cyclopentyl-5-((trimethylsilyl)ethynyl)pyrimidin -4-amine (1383481-56-8)

Conditions	Yield
With 1-methyl-pyrrolidin-2-one; bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; for 8h; Inert atmosphere;	53.1%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + 4-(5-aminopyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (119285-07-3) → 4-[5-(5-BROMO-4-CYCLOPENTYLAMINOPYRIMIDIN-2-YLAMINO)-PYNIDIN-2-YL]-PIPERAZINE-1-CARBOXYLIC acid tert-butyl ester (733039-28-6)

Conditions	Yield
With sodium t-butanolate In toluene at 115℃; for 48h;	45%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + 4-amino-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide (876126-60-2) → C23H31BrN6O2

Conditions	Yield
With hydrogenchloride In water; isopropyl alcohol at 80℃; for 18h;	31%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + Methyl 2-butynoate (23326-27-4) → 2-chloro-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl ester (959799-27-0)

Conditions	Yield
With potassium carbonate; lithium chloride; palladium diacetate In N,N-dimethyl-formamide at 120℃; for 5h;	25%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) + Pent-3-yn-2-ol (57984-70-0, 58072-60-9, 90242-65-2, 27301-54-8) → 1-(2-Chloro-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-ethanol (959799-21-4)

Conditions	Yield
With potassium acetate; lithium chloride; palladium diacetate In N,N-dimethyl-formamide at 120℃; for 5h;	14.8%

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) → 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (1211443-61-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: tetrabutyl ammonium fluoride / bis-triphenylphosphine-palladium(II) chloride / water; tetrahydrofuran / 2 h / 25 - 67 °C / Inert atmosphere 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.67 h / 25 - 60 °C / Inert atmosphere 3: sodium cyanide / N,N-dimethyl-formamide; tetrahydrofuran / 4.25 h / 17 - 23 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1: 1,4-diaza-bicyclo[2.2.2]octane; copper(l) iodide; bis-triphenylphosphine-palladium(II) chloride / acetonitrile / 0 - 60 °C / Inert atmosphere 2: copper(l) chloride; 1,8-diazabicyclo[5.4.0]undec-7-ene / N,N-dimethyl-formamide / 85 - 90 °C / Inert atmosphere 3: sodium hydroxide / methanol; water / 10 - 25 °C 4: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / N,N-dimethyl-formamide; tetrahydrofuran / 0 - 25 °C View Scheme
Multi-step reaction with 3 steps 1.1: triphenylphosphine; palladium dichloride / N,N-dimethyl-formamide / 20 h / 50 °C 2.1: tetrabutyl ammonium fluoride / ethanol / 16 h / 60 °C 3.1: N-Bromosuccinimide / 1,2-dichloro-ethane / 3 h / 20 °C / Sealed tube 3.2: 24 h / 100 °C / Sealed tube View Scheme

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) → (7-cyclopentyl-Ν,Ν-dimethyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrrolo [2,3-d]pyrimidine-6-carboxamide) (1211441-98-3)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: tetrabutyl ammonium fluoride / bis-triphenylphosphine-palladium(II) chloride / water; tetrahydrofuran / 2 h / 25 - 67 °C / Inert atmosphere 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.67 h / 25 - 60 °C / Inert atmosphere 3.1: sodium cyanide / N,N-dimethyl-formamide; tetrahydrofuran / 4.25 h / 17 - 23 °C / Inert atmosphere 4.1: caesium carbonate / palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl / 4-methyl-2-pentanone / 3.25 h / 37 - 103 °C / Inert atmosphere 5.1: hydrogenchloride; water / toluene / 1.08 h / 9 - 28 °C / Inert atmosphere 5.2: Si-thiol functionalized silica gel / 6 h / 30 - 53 °C / pH 2.9 - 3.5 View Scheme
Multi-step reaction with 5 steps 1.1: triphenylphosphine; palladium dichloride / N,N-dimethyl-formamide / 20 h / 50 °C 2.1: tetrabutyl ammonium fluoride / ethanol / 16 h / 60 °C 3.1: N-Bromosuccinimide / 1,2-dichloro-ethane / 3 h / 20 °C / Sealed tube 3.2: 24 h / 100 °C / Sealed tube 4.1: potassium carbonate / dichloromethane / 0.5 h / 60 °C 4.2: 1 h / 60 °C 5.1: phosphoric acid / dichloromethane View Scheme
Multi-step reaction with 5 steps 1.1: isopropylmagnesium chloride / tetrahydrofuran / 0 - 5 °C / Inert atmosphere 1.2: 20 °C / Inert atmosphere 2.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 45 - 50 °C 3.1: potassium tert-butylate / N,N-dimethyl-formamide / 0 - 30 °C 4.1: sodium t-butanolate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / N,N-dimethyl acetamide / 0 - 110 °C / Inert atmosphere 5.1: hydrogenchloride / methanol; water / 10 - 25 °C View Scheme
Multi-step reaction with 7 steps 1.1: isopropylmagnesium chloride / tetrahydrofuran / 0 - 5 °C / Inert atmosphere 1.2: 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 45 - 50 °C 3.1: potassium tert-butylate / N,N-dimethyl-formamide / 0 - 30 °C 4.1: sodium hydroxide / methanol; water / 10 - 45 °C 5.1: triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran; N,N-dimethyl-formamide / 0 - 25 °C 6.1: sodium t-butanolate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / N,N-dimethyl acetamide / 0 - 110 °C / Inert atmosphere 7.1: hydrogenchloride / methanol; water / 10 - 25 °C View Scheme
Multi-step reaction with 7 steps 1.1: isopropylmagnesium chloride / tetrahydrofuran / 0 - 5 °C / Inert atmosphere 1.2: 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 45 - 50 °C 3.1: potassium tert-butylate / N,N-dimethyl-formamide / 0 - 30 °C 4.1: caesium carbonate; palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl / 1,4-dioxane / 0 - 110 °C / Inert atmosphere 5.1: lithium hydroxide monohydrate / methanol; water / 10 - 45 °C 6.1: N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran; N,N-dimethyl-formamide / 0 - 30 °C 7.1: hydrogenchloride / methanol; water / 10 - 25 °C View Scheme

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) → (2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)methanol (1374639-77-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrabutyl ammonium fluoride / bis-triphenylphosphine-palladium(II) chloride / water; tetrahydrofuran / 2 h / 25 - 67 °C / Inert atmosphere 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.67 h / 25 - 60 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: N-butylamine; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / tetrahydrofuran / 20 h / 29 °C / Inert atmosphere; Reflux 2: trifluoroacetic acid / tetrahydrofuran / 12 h / 29 - 60 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; tetrabutyl ammonium fluoride / tetrahydrofuran / 5 h / 70 °C 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 12 h / 70 °C View Scheme

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) → 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
Multi-step reaction with 4 steps 1: tetrabutyl ammonium fluoride / bis-triphenylphosphine-palladium(II) chloride / water; tetrahydrofuran / 2 h / 25 - 67 °C / Inert atmosphere 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.67 h / 25 - 60 °C / Inert atmosphere 3: sodium cyanide / N,N-dimethyl-formamide; tetrahydrofuran / 4.25 h / 17 - 23 °C / Inert atmosphere 4: caesium carbonate / palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl / 4-methyl-2-pentanone / 3.25 h / 37 - 103 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: triphenylphosphine; palladium dichloride / N,N-dimethyl-formamide / 20 h / 50 °C 2.1: tetrabutyl ammonium fluoride / ethanol / 16 h / 60 °C 3.1: N-Bromosuccinimide / 1,2-dichloro-ethane / 3 h / 20 °C / Sealed tube 3.2: 24 h / 100 °C / Sealed tube 4.1: potassium carbonate / dichloromethane / 0.5 h / 60 °C 4.2: 1 h / 60 °C View Scheme
Multi-step reaction with 4 steps 1.1: isopropylmagnesium chloride / tetrahydrofuran / 0 - 5 °C / Inert atmosphere 1.2: 20 °C / Inert atmosphere 2.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 45 - 50 °C 3.1: potassium tert-butylate / N,N-dimethyl-formamide / 0 - 30 °C 4.1: sodium t-butanolate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / N,N-dimethyl acetamide / 0 - 110 °C / Inert atmosphere View Scheme
Multi-step reaction with 6 steps 1.1: isopropylmagnesium chloride / tetrahydrofuran / 0 - 5 °C / Inert atmosphere 1.2: 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 45 - 50 °C 3.1: potassium tert-butylate / N,N-dimethyl-formamide / 0 - 30 °C 4.1: caesium carbonate; palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl / 1,4-dioxane / 0 - 110 °C / Inert atmosphere 5.1: lithium hydroxide monohydrate / methanol; water / 10 - 45 °C 6.1: N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran; N,N-dimethyl-formamide / 0 - 30 °C View Scheme
Multi-step reaction with 6 steps 1.1: isopropylmagnesium chloride / tetrahydrofuran / 0 - 5 °C / Inert atmosphere 1.2: 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 45 - 50 °C 3.1: potassium tert-butylate / N,N-dimethyl-formamide / 0 - 30 °C 4.1: sodium hydroxide / methanol; water / 10 - 45 °C 5.1: triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran; N,N-dimethyl-formamide / 0 - 25 °C 6.1: sodium t-butanolate; [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate / N,N-dimethyl acetamide / 0 - 110 °C / Inert atmosphere View Scheme

5-bromo-2-chloro-N-cyclopentylaminopyrimidine-4-amine (733039-20-8) → 7-cyclopentyl-N,N-dimethyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide succinate

Conditions

Yield

Multi-step reaction with 6 steps 1.1: tetrabutyl ammonium fluoride / bis-triphenylphosphine-palladium(II) chloride / water; tetrahydrofuran / 2 h / 25 - 67 °C / Inert atmosphere 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1.67 h / 25 - 60 °C / Inert atmosphere 3.1: sodium cyanide / N,N-dimethyl-formamide; tetrahydrofuran / 4.25 h / 17 - 23 °C / Inert atmosphere 4.1: caesium carbonate / palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl / 4-methyl-2-pentanone / 3.25 h / 37 - 103 °C / Inert atmosphere 5.1: hydrogenchloride; water / toluene / 1.08 h / 9 - 28 °C / Inert atmosphere 5.2: Si-thiol functionalized silica gel / 6 h / 30 - 53 °C / pH 2.9 - 3.5 6.1: isopropyl alcohol / 27 - 83 °C / Inert atmosphere View Scheme

Upstream product

• 36082-50-5 2,4-dichloro-5-bromopyrimidine 
• 1003-03-8 Cyclopentamine 
• 930-28-9 cyclopentyl chloride 
• 205672-25-9 4-amino-5-bromo-2-chloropyrimidine 
• 137-43-9 Cyclopentyl bromide 

Downstream Products

• 1013916-37-4 2-chloro-5-methyl-8-cyclopentylpyridin[2,3-d]pyrimidin-8-hydro-7-one 
• 733039-23-1 5?bromo?N?cyclopentyl?2?(methylthio)pyrimidin?4?amine 
• 733038-80-7 tert-butyl 4-(6-{[5-bromo-4-(cyclopentylamino)pyrimidin-2-yl]amino}pyridin-3-yl)piperazine-1-carboxylate 
• 959799-27-0 2-chloro-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl ester 
• 1374639-76-5 3-(2-chloro-4-(cyclopentylamino)pyrimidin-5-yl)prop-2-yn-1-ol 
• 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 
• 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 
• 1383481-70-6 C₃₂H₃₇N₉O 
• 1383481-45-5 C₁₈H₁₉N₅O₃ 
• 1383481-46-6 C₂₃H₂₉N₇O₂ 
• 1383481-65-9 C₂₁H₂₀ClN₅ 
• 1016636-76-2 2-chloro-5-methyl-6-bromo-8-cyclopentylpyridine[2,3-d]pyrimidin-8-hydro-7-one 
• 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 
• 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 

Relevant articles and documents

Preparation method of palbociclib intermediate

The invention discloses a preparation method of a palbociclib intermediate. The method comprises the following steps: preparing 5-bromine-2-chloro-N-cyclopentylamine pyrimidine-4 amine from 5-bromine-2,4-dichloropyrimidine and cyclopentylamine by taking solvents such as dichloromethane and water as solvents and taking inorganic base as an acid-binding agent; with DIEA as an acid-binding agent, DMF as a solvent and TBAB as a phase transfer catalyst, in the presence of water, catalyzing with a trace amount of palladium, and carrying out normal hexane reflux dehydration; further subjecting the acetic anhydride to dehydration cyclization, such that 2-chloro-8-cyclopentyl-5-methylpyridino[2,3-D]pyrimidine-7-(8H)-ketone is obtained; and reacting the obtained compound with NBS (N-bromosuccinimide) in acetonitrile to obtain the 6-bromo-2-chloro-8-cyclopentyl-5-methylpyridino[2, 3-D]pyrimidine-7(8H)-ketone. The method is mild in reaction, simple and convenient to operate, recyclable in solvent, less in environmental pollution, high in yield, low in cost, high in product quality and suitable for industrial production.

Synthesis and cytotoxic studies of pyrrolopyrimidine derivatives

The synthesis and in vitro cytotoxicity of new pyrrolopyrimidine derivatives is reported in this work. All the compounds were characterized by IR, NMR and MS. They are examined for cytotoxic activity against HeLa. Pyrrolopyrimidine derivatives of benzyl amine (8g) and 4-bromoaniline (8k) showed a potent activity, which is comparable to that of standard Sorafenib.

Discovery of 5-methylpyrimidopyridone analogues as selective antimycobacterial agents

With the emergence of multidrug-resistant strains of Mycobacterium tuberculosis (MDR-TB) and extensive drug-resistant strains (XDR-TB), there is an urgent need to develop novel drugs for the treatment of tuberculosis. Here, we designed and synthesized a series of 5-methylpyrimidopyridone analogues as potential antitubercular agents. The most potent compound 6q exhibited a MIC value of 4 μM in vitro against Mycobacterium tuberculosis. The antitubercular activities of the synthesized compounds were impacted by the amantadine and 2-chlorophenyl groups, and were enhanced by the presence of 3-methyl(4-dimethylamino)piperidinylphenyl. Molecular modeling and binding studies suggest that PknB is the potential molecular target of 5-methylpyrimidopyridone compounds. This study provides insights for the future development of new antimycobacterial agents with novel mechanisms of action.