571188-81-3

Basic information

• Product Name: 6-BroMo-8-cyclopentyl-2-Methanesulfinyl-5-Methyl-8H-pyrido[2,3-d]pyriMidin-7-one
• Synonyms: 6-bromo-8-cyclopentyl-5-methyl-2-(methylsulfinyl)pyrido[2,3-d]pyrimidin-7(8H)-one;6-Bromo-8-cyclopentyl-2-methylsulfinyl-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one
• CAS NO: 571188-81-3
• Molecular Formula: C₁₄H₁₆BrN₃O₂S
• Molecular Weight: 370.26474
• Mol File: 571188-81-3.mol
• Article Data: 11

Chemical Properties

• Boiling Point: 542.8±60.0 °C(Predicted)
• Appearance: /
• Density: 1.66±0.1 g/cm3(Predicted)
• Storage Temp.: -20°C Freezer
• Solubility: Chloroform (Slightly), Methanol (Slightly, Heated)
• PKA: -1.69±0.20(Predicted)
• CAS DataBase Reference: 6-BroMo-8-cyclopentyl-2-Methanesulfinyl-5-Methyl-8H-pyrido[2,3-d]pyriMidin-7-one(CAS DataBase Reference)
• NIST Chemistry Reference: 6-BroMo-8-cyclopentyl-2-Methanesulfinyl-5-Methyl-8H-pyrido[2,3-d]pyriMidin-7-one(571188-81-3)
• EPA Substance Registry System: 6-BroMo-8-cyclopentyl-2-Methanesulfinyl-5-Methyl-8H-pyrido[2,3-d]pyriMidin-7-one(571188-81-3)

Safety Data

• Hazardous Substances Data: 571188-81-3(Hazardous Substances Data)

Usage

Description

6-Bromo-8-cyclopentyl-2-Methanesulfinyl-5-Methyl-8H-pyrido[2,3-d]pyriMidin-7-one is a complex organic compound characterized by its unique molecular structure. It is a derivative of pyrido[2,3-d]pyrimidin-7(8H)-one, which is known for its potential applications in various fields due to its specific chemical properties.

Uses

Used in Pharmaceutical Industry:
6-Bromo-8-cyclopentyl-2-Methanesulfinyl-5-Methyl-8H-pyrido[2,3-d]pyriMidin-7-one is used as a reactant for the preparation of pyrido[2,3-d]pyrimidin-7-one derivatives. These derivatives are selective inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6), which play a crucial role in regulating cell cycle progression. By inhibiting CDK4/6, these derivatives have the potential to be developed into therapeutic agents for the treatment of various types of cancer, as uncontrolled cell proliferation is a hallmark of cancerous cells.
6-BroMo-8-cyclopentyl-2-Methanesulfinyl-5-Methyl-8H-pyrido[2,3-d]pyriMidin-7-one's application in the pharmaceutical industry is primarily due to its ability to target and inhibit specific cellular processes that contribute to the development and progression of cancer. This selective inhibition can potentially lead to the development of more effective and targeted cancer treatments with fewer side effects compared to conventional chemotherapy.

Synthetic route

6-bromo-8-cyclopentyl-5-methyl-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one (362656-25-5) → 6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3)

Conditions	Yield
With 2-benzylsulfonyl-3-phenyloxaziridine In dichloromethane	94%
With N-(benzenesulfonyl)-3-phenyloxaziridine In dichloromethane at 20℃; for 18h;	40.9%
With N-(benzenesulfonyl)-3-phenyloxaziridine In dichloromethane at 20℃; for 18h;

8‑cyclopentyl‑5‑methyl‑2‑(methylthio)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (362656-23-3) → 6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3)

Conditions	Yield
With N-Bromosuccinimide; acetic acid In water; acetonitrile for 2h;	87%
With N-Bromosuccinimide; acetic acid In water; acetonitrile at 20℃; for 8h;	85.6%
With N-Bromosuccinimide; water; acetic acid In acetonitrile at 20℃; for 8h;	85.6%

4-chloro-2-methanesulfanylpyrimidine-5-carboxylic acid ethyl ester (5909-24-0) → 6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: triethylamine / dichloromethane 2.1: lithium aluminium tetrahydride / tetrahydrofuran 3.1: manganese(IV) oxide / chloroform 4.1: tetrahydrofuran; diethyl ether / 1 h / Inert atmosphere; Cooling with ice 4.2: 22 h / Reflux 5.1: sodium hydride / tetrahydrofuran 6.1: N-Bromosuccinimide / N,N-dimethyl-formamide / 3.5 h / 20 °C View Scheme
Multi-step reaction with 7 steps 1.1: triethylamine / tetrahydrofuran / 14 h / 20 °C 2.1: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / 12 - 20 °C 3.1: manganese(IV) oxide / chloroform / 16 h / 20 °C 4.1: tetrahydrofuran / 1.5 h / Inert atmosphere; Cooling with ice 4.2: 16 h / 20 °C 5.1: sodium hydride / tetrahydrofuran; mineral oil / 36 h / Inert atmosphere; Cooling; Reflux 6.1: bromine / dichloromethane / 16 h / 20 °C 7.1: N-(benzenesulfonyl)-3-phenyloxaziridine / dichloromethane / 18 h / 20 °C View Scheme
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane 2: lithium aluminium tetrahydride / tetrahydrofuran 3: manganese(IV) oxide / chloroform 4: tetrahydrofuran; diethyl ether / Inert atmosphere; Cooling with ice 5: manganese(IV) oxide / chloroform / 22 h / Reflux 6: sodium hydride / tetrahydrofuran 7: N-Bromosuccinimide / N,N-dimethyl-formamide / 3.5 h / 20 °C View Scheme

Cyclopentamine (1003-03-8) → 6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: triethylamine / dichloromethane 2.1: lithium aluminium tetrahydride / tetrahydrofuran 3.1: manganese(IV) oxide / chloroform 4.1: tetrahydrofuran; diethyl ether / 1 h / Inert atmosphere; Cooling with ice 4.2: 22 h / Reflux 5.1: sodium hydride / tetrahydrofuran 6.1: N-Bromosuccinimide / N,N-dimethyl-formamide / 3.5 h / 20 °C View Scheme
Multi-step reaction with 7 steps 1.1: triethylamine / tetrahydrofuran / 14 h / 20 °C 2.1: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / 12 - 20 °C 3.1: manganese(IV) oxide / chloroform / 16 h / 20 °C 4.1: tetrahydrofuran / 1.5 h / Inert atmosphere; Cooling with ice 4.2: 16 h / 20 °C 5.1: sodium hydride / tetrahydrofuran; mineral oil / 36 h / Inert atmosphere; Cooling; Reflux 6.1: bromine / dichloromethane / 16 h / 20 °C 7.1: N-(benzenesulfonyl)-3-phenyloxaziridine / dichloromethane / 18 h / 20 °C View Scheme
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane 2: lithium aluminium tetrahydride / tetrahydrofuran 3: manganese(IV) oxide / chloroform 4: tetrahydrofuran; diethyl ether / Inert atmosphere; Cooling with ice 5: manganese(IV) oxide / chloroform / 22 h / Reflux 6: sodium hydride / tetrahydrofuran 7: N-Bromosuccinimide / N,N-dimethyl-formamide / 3.5 h / 20 °C View Scheme

4-cyclopentylamino-2-methylsulfanyl-pyrimidine-5-carbaldehyde (211245-64-6) → 6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: tetrahydrofuran; diethyl ether / 1 h / Inert atmosphere; Cooling with ice 1.2: 22 h / Reflux 2.1: sodium hydride / tetrahydrofuran 3.1: N-Bromosuccinimide / N,N-dimethyl-formamide / 3.5 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: tetrahydrofuran / 1.5 h / Inert atmosphere; Cooling with ice 1.2: 16 h / 20 °C 2.1: sodium hydride / tetrahydrofuran; mineral oil / 36 h / Inert atmosphere; Cooling; Reflux 3.1: bromine / dichloromethane / 16 h / 20 °C 4.1: N-(benzenesulfonyl)-3-phenyloxaziridine / dichloromethane / 18 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1: tetrahydrofuran; diethyl ether / Inert atmosphere; Cooling with ice 2: manganese(IV) oxide / chloroform / 22 h / Reflux 3: sodium hydride / tetrahydrofuran 4: N-Bromosuccinimide / N,N-dimethyl-formamide / 3.5 h / 20 °C View Scheme

4-cyclopentylamino-2-(methylsulfanyl)pyrimidine-5-carboxylic acid ethyl ester (211245-62-4) → 6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran 2.1: manganese(IV) oxide / chloroform 3.1: tetrahydrofuran; diethyl ether / 1 h / Inert atmosphere; Cooling with ice 3.2: 22 h / Reflux 4.1: sodium hydride / tetrahydrofuran 5.1: N-Bromosuccinimide / N,N-dimethyl-formamide / 3.5 h / 20 °C View Scheme
Multi-step reaction with 6 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / 12 - 20 °C 2.1: manganese(IV) oxide / chloroform / 16 h / 20 °C 3.1: tetrahydrofuran / 1.5 h / Inert atmosphere; Cooling with ice 3.2: 16 h / 20 °C 4.1: sodium hydride / tetrahydrofuran; mineral oil / 36 h / Inert atmosphere; Cooling; Reflux 5.1: bromine / dichloromethane / 16 h / 20 °C 6.1: N-(benzenesulfonyl)-3-phenyloxaziridine / dichloromethane / 18 h / 20 °C View Scheme
Multi-step reaction with 6 steps 1: lithium aluminium tetrahydride / tetrahydrofuran 2: manganese(IV) oxide / chloroform 3: tetrahydrofuran; diethyl ether / Inert atmosphere; Cooling with ice 4: manganese(IV) oxide / chloroform / 22 h / Reflux 5: sodium hydride / tetrahydrofuran 6: N-Bromosuccinimide / N,N-dimethyl-formamide / 3.5 h / 20 °C View Scheme

[4-cyclopentylamino-2-(methylsulfanyl)pyrimidine-5-yl]methanol (211245-63-5) → 6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: manganese(IV) oxide / chloroform 2.1: tetrahydrofuran; diethyl ether / 1 h / Inert atmosphere; Cooling with ice 2.2: 22 h / Reflux 3.1: sodium hydride / tetrahydrofuran 4.1: N-Bromosuccinimide / N,N-dimethyl-formamide / 3.5 h / 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: manganese(IV) oxide / chloroform / 16 h / 20 °C 2.1: tetrahydrofuran / 1.5 h / Inert atmosphere; Cooling with ice 2.2: 16 h / 20 °C 3.1: sodium hydride / tetrahydrofuran; mineral oil / 36 h / Inert atmosphere; Cooling; Reflux 4.1: bromine / dichloromethane / 16 h / 20 °C 5.1: N-(benzenesulfonyl)-3-phenyloxaziridine / dichloromethane / 18 h / 20 °C View Scheme

1-(4-(cyclopentylamino)-2-(methylthio)pyrimidin-5-yl)ethanone (362656-11-9) → 6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydride / tetrahydrofuran 2: N-Bromosuccinimide / N,N-dimethyl-formamide / 3.5 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: sodium hydride / tetrahydrofuran; mineral oil / 36 h / Inert atmosphere; Cooling; Reflux 2: bromine / dichloromethane / 16 h / 20 °C 3: N-(benzenesulfonyl)-3-phenyloxaziridine / dichloromethane / 18 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: sodium hydride / tetrahydrofuran 2: N-Bromosuccinimide / N,N-dimethyl-formamide / 3.5 h / 20 °C View Scheme

1-(4-cyclopentylamino-2-methylsulfanylpyrimidin-5-yl)ethanol (362656-31-3) → 6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: manganese(IV) oxide / chloroform / 22 h / Reflux 2: sodium hydride / tetrahydrofuran 3: N-Bromosuccinimide / N,N-dimethyl-formamide / 3.5 h / 20 °C View Scheme

4-(cyclopentylamino)-2-(methylthio)pyrimidine-5-carboxylic acid (1065075-68-4) → 6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: manganese(IV) oxide / chloroform 2: tetrahydrofuran; diethyl ether / Inert atmosphere; Cooling with ice 3: manganese(IV) oxide / chloroform / 22 h / Reflux 4: sodium hydride / tetrahydrofuran 5: N-Bromosuccinimide / N,N-dimethyl-formamide / 3.5 h / 20 °C View Scheme

2-Methylthiouracil (5751-20-2) → 6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: N-Bromosuccinimide / dichloromethane / 6 h / Reflux 2.1: pyridine; trichlorophosphate / 5 h / 80 °C 3.1: triethylamine / tetrahydrofuran / 2.5 h / Cooling with ice 4.1: triethylamine; lead acetate / 1-methyl-pyrrolidin-2-one / 3.5 h / 65 °C / Inert atmosphere 4.2: 8 h / 65 °C / Inert atmosphere 5.1: N-Bromosuccinimide; acetic acid / acetonitrile; water / 2 h View Scheme
Multi-step reaction with 5 steps 1.1: thionyl chloride / N,N-dimethyl-formamide; dichloromethane / 3 h / 40 °C 2.1: N-Bromosuccinimide / methanol; acetonitrile / 20 °C 3.1: N-ethyl-N,N-diisopropylamine / 1,4-dioxane / 4 h / 100 °C 4.1: N-ethyl-N,N-diisopropylamine; bis(benzonitrile)palladium(II) dichloride; tris-(o-tolyl)phosphine / N,N-dimethyl-formamide / 24 h / 130 °C / Inert atmosphere 4.2: 4 h / 70 °C 5.1: N-Bromosuccinimide; acetic acid / acetonitrile; water / 8 h / 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: thionyl chloride; N,N-dimethyl-formamide / dichloromethane / 3 h / 40 °C 2.1: N-Bromosuccinimide / methanol; acetonitrile 3.1: N-ethyl-N,N-diisopropylamine / 1,4-dioxane / 4 h / 100 °C 4.1: N-ethyl-N,N-diisopropylamine; tris-(o-tolyl)phosphine / N,N-dimethyl-formamide / 24 h / 130 °C / Inert atmosphere 4.2: 4 h / 70 °C 5.1: N-Bromosuccinimide; acetic acid; water / acetonitrile / 8 h / 20 °C View Scheme

2-methylsulfanyl-5-bromopyrimidin-4-one (81560-03-4) → 6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: pyridine; trichlorophosphate / 5 h / 80 °C 2.1: triethylamine / tetrahydrofuran / 2.5 h / Cooling with ice 3.1: triethylamine; lead acetate / 1-methyl-pyrrolidin-2-one / 3.5 h / 65 °C / Inert atmosphere 3.2: 8 h / 65 °C / Inert atmosphere 4.1: N-Bromosuccinimide; acetic acid / acetonitrile; water / 2 h View Scheme

4‑chloro‑5‑bromo‑2‑(methylthio)pyrimidine (63810-78-6) → 6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: triethylamine / tetrahydrofuran / 2.5 h / Cooling with ice 2.1: triethylamine; lead acetate / 1-methyl-pyrrolidin-2-one / 3.5 h / 65 °C / Inert atmosphere 2.2: 8 h / 65 °C / Inert atmosphere 3.1: N-Bromosuccinimide; acetic acid / acetonitrile; water / 2 h View Scheme
Multi-step reaction with 3 steps 1.1: N-ethyl-N,N-diisopropylamine / 1,4-dioxane / 4 h / 100 °C 2.1: N-ethyl-N,N-diisopropylamine; bis(benzonitrile)palladium(II) dichloride; tris-(o-tolyl)phosphine / N,N-dimethyl-formamide / 24 h / 130 °C / Inert atmosphere 2.2: 4 h / 70 °C 3.1: N-Bromosuccinimide; acetic acid / acetonitrile; water / 8 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: N-ethyl-N,N-diisopropylamine / 1,4-dioxane / 4 h / 100 °C 2.1: N-ethyl-N,N-diisopropylamine; tris-(o-tolyl)phosphine / N,N-dimethyl-formamide / 24 h / 130 °C / Inert atmosphere 2.2: 4 h / 70 °C 3.1: N-Bromosuccinimide; acetic acid; water / acetonitrile / 8 h / 20 °C View Scheme

4-Chloro-2-methylthiopyrimidine (49844-90-8) → 6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: N-Bromosuccinimide / methanol; acetonitrile / 20 °C 2.1: N-ethyl-N,N-diisopropylamine / 1,4-dioxane / 4 h / 100 °C 3.1: N-ethyl-N,N-diisopropylamine; bis(benzonitrile)palladium(II) dichloride; tris-(o-tolyl)phosphine / N,N-dimethyl-formamide / 24 h / 130 °C / Inert atmosphere 3.2: 4 h / 70 °C 4.1: N-Bromosuccinimide; acetic acid / acetonitrile; water / 8 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: N-Bromosuccinimide / methanol; acetonitrile 2.1: N-ethyl-N,N-diisopropylamine / 1,4-dioxane / 4 h / 100 °C 3.1: N-ethyl-N,N-diisopropylamine; tris-(o-tolyl)phosphine / N,N-dimethyl-formamide / 24 h / 130 °C / Inert atmosphere 3.2: 4 h / 70 °C 4.1: N-Bromosuccinimide; acetic acid; water / acetonitrile / 8 h / 20 °C View Scheme

5‑bromo‑N‑cyclopentyl‑2‑(methylthio)pyrimidin‑4‑amine (733039-23-1) → 6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine; tris-(o-tolyl)phosphine / N,N-dimethyl-formamide / 24 h / 130 °C / Inert atmosphere 1.2: 4 h / 70 °C 2.1: N-Bromosuccinimide; acetic acid; water / acetonitrile / 8 h / 20 °C View Scheme

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) + 4-methoxy-benzylamine (2393-23-9) → 6-bromo-8-cyclopentyl-2-(4-methoxybenzylamino)-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (571190-14-2)

Conditions	Yield
In toluene	86.4%

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) + N5,N5-bis(2-methoxyethyl)pyridine-2,5-diamine → 2-{5-[bis-(2-methoxy-ethyl)amino]pyridin-2-ylamino}-6-bromo-8-cyclopentyl-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (571189-32-7)

Conditions	Yield
In toluene at 110℃; for 5h;	85%
In ethyl acetate; toluene	85%

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) + 4-(4-aminophenyl)-1-t-butyloxycarbonylpiperazine (170911-92-9) → 4-[4-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)phenyl]-piperazine-1-carboxylic acid tert-butyl ester (362656-71-1)

Conditions	Yield
In dimethyl sulfoxide at 100℃;	81%

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) + tert-butyl 4-(6-aminopyridin-3-yl)-1,4-homopiperazine-1-carboxylate → 4-[6-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)pyridin-3-yl]azepane-1-carboxylic acid tert-butyl ester (887906-41-4)

Conditions	Yield
In toluene for 12h; Heating;	39%

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) + 4-(6-amino-pyridin-3-yl)-2,6-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (571189-73-6) → 4-[6-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)pyridin-3-yl]-2,6-dimethylpiperazine-1-carboxylic acid tert-butyl ester (571189-74-7)

Conditions	Yield
In toluene for 16h; Heating;	38%
In toluene	37.6%

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) + tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (571188-59-5) → 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
In toluene for 7h; Heating;	38%
In toluene for 25h; Heating / reflux;	38%
In toluene	38%

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) + 4-(6-amino-pyridin-3-yl)-2,2-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (571189-68-9) → 4-[6-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)pyridin-3-yl]-2,2-dimethylpiperazine-1-carboxylic acid tert-butyl ester (571189-69-0)

Conditions	Yield
In toluene for 16h; Heating;	32%

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) + 4-(6-amino-pyridin-3-yl)-2,2-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (571189-68-9) → 4-[6-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)pyridin-3-yl]-2,2-dimethylpiperazine-1-carboxylic acid tert-butyl ester (571189-69-0) + 4-[6-(6-Bromo-8-cyclopentyl-5-methyl-1-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)-pyridin-3-yl]-2,2-dimethyl-piperazine-1-carboxylic Acid Tert-butyl Ester

Conditions	Yield
In toluene	A n/a B 31.8%

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) + 2-aminopyridine (504-29-0) → 6-bromo-8-cyclopentyl-5-methyl-2-(pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one

Conditions	Yield
In toluene	30%
In toluene at 110℃; for 18h;	22 mg

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) + 5-(4-methyl-piperazin-1-yl)pyridin-2-ylamine (571189-49-6) → 6-bromo-8-cyclopentyl-5-methyl-2-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-8H-pyrido[2,3-d]pyrimidin-7-one; compound with GENERIC INORGANIC NEUTRAL COMPONENT

Conditions	Yield
In toluene for 4h; Heating;	29%

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) + 3,4,5,6-tetrahydro-2H-[1,3']bipyridinyl-6'-ylamine (94924-94-4) → 6-bromo-8-cyclopentyl-5-methyl-2-(3,4,5,6-tetrahydro-2H-[1,3']bipyridinyl-6'-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one (571189-82-7)

Conditions	Yield
In toluene for 16h; Heating;	27%
In toluene	27.3%

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) + 5-(2,6-dimethylmorpholin-4-yl)pyridin-2-ylamine (571190-02-8) → 6-bromo-8-cyclopentyl-2-[5-(2,6-dimethylmorpholin-4-yl)pyridin-2-ylamino]-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (571190-03-9)

Conditions	Yield
In toluene for 16h; Heating;	27%
In toluene	27.3%

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) + 5-morpholinopyridin-2-amine (571189-78-1) → 6-bromo-8-cyclopentyl-5-methyl-2-(5-morpholin-4-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one (571189-79-2)

Conditions	Yield
In toluene for 16h; Heating;	27%
In ethyl acetate; toluene	26.7%

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) + 6'-amino-3,4,5,6-tetrahydro-2H-[1,3']bipyridinyl-4-ol (571189-27-0) → 6-bromo-8-cyclopentyl-2-(4-hydroxy-3,4,5,6-tetrahydro-2H-[1,3']bipyridinyl-6'-ylamino)-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (571189-55-4)

Conditions	Yield
In toluene for 4h; Heating;	17%
In toluene

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) + 2-amino-5-(5-benzylhexahydropyrrolo[3,4-c]pyrrole-2(1H)-yl)pyridine → 2-(5-(5-benzylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridin-2-ylamino)-6-bromo-8-cyclopentyl-5-methylpyrido[2,3-d]pyrimidin-7(8H)-one

Conditions	Yield
In toluene for 18h; Inert atmosphere; Reflux;	7.4%

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) + tert-butyl [1-(6-aminopyridin-3-yl)pyrrolidin-3-yl]carbamate → {1-[6-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)pyridin-3-yl]pyrrolidin-3-yl}carbamic acid tert-butyl ester (571189-53-2)

Conditions	Yield
In toluene for 16h; Heating;

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) → 6-Bromo-8-cyclopentyl-2-[5-(3,5-dimethyl-piperazin-1-yl)-pyridin-2-ylamino]-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one

Conditions	Yield
Multi-step reaction with 2 steps 1: 38 percent / toluene / 16 h / Heating 2: aq. HCl / CH2Cl2 / 20 °C View Scheme

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) → 6-acetyl-8-cyclopentyl-2-[5-(2,6-dimethylmorpholin-4-yl)pyridin-2-ylamino]-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one

Conditions	Yield
Multi-step reaction with 3 steps 1: 27 percent / toluene / 16 h / Heating 2: 90 percent / tetrakis(triphenylphosphine)palladium(0) / toluene / 12 h / Heating 3: 38 percent / aq. HCl / ethyl acetate / 48 h / 20 °C View Scheme

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) → 6-acetyl-8-cyclopentyl-5-methyl-2-(3,4,5,6-tetrahydro-2H-[1,3']bipyridinyl-6'-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one

Conditions	Yield
Multi-step reaction with 3 steps 1: 27 percent / toluene / 16 h / Heating 2: 59 percent / tetrakis(triphenylphosphine)palladium(0) / toluene / 2 h / Heating 3: 71 percent / aq. HCl / ethyl acetate / 2 h / 20 °C View Scheme

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) → 6-acetyl-8-cyclopentyl-5-methyl-2-(5-morpholin-4-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one

Conditions	Yield
Multi-step reaction with 3 steps 1: 27 percent / toluene / 16 h / Heating 2: 39 percent / tetrakis(triphenylphosphine)palladium(0) / toluene / 3 h / Heating 3: HCl / CH2Cl2; diethyl ether / 16 h / 20 °C View Scheme

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) → 6-acetyl-2-{5-[bis-(2-methoxy-ethyl)amino]pyridin-2-ylamino}-8-cyclopentyl-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one

Conditions	Yield
Multi-step reaction with 3 steps 1: 85 percent / toluene / 5 h / 110 °C 2: palladium tetrakistriphenylphosphine / toluene / 2 h / 110 °C 3: 120 mg / aq. HCl / ethyl acetate / 1 h / 20 °C View Scheme

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) → 6-acetyl-8-cyclopentyl-2-(4-hydroxy-3,4,5,6-tetrahydro-2H-[1,3']bipyridinyl-6'-ylamino)-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one

Conditions	Yield
Multi-step reaction with 3 steps 1: 17 percent / toluene / 4 h / Heating 2: 83 percent / tetrakis(triphenylphosphine)palladium(0) / toluene / 12 h / 110 °C 3: 88 percent / HCl / CHCl3; diethyl ether / 12 h / 20 °C View Scheme

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) → 8-cyclopentyl-2-[5-(2,6-dimethylmorpholin-4-yl)pyridin-2-ylamino]-6-(1-ethoxyvinyl)-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (571190-10-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 27 percent / toluene / 16 h / Heating 2: 90 percent / tetrakis(triphenylphosphine)palladium(0) / toluene / 12 h / Heating View Scheme

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) → 8-cyclopentyl-6-(1-ethoxyvinyl)-5-methyl-2-(5-morpholin-4-ylpyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one (571189-80-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 27 percent / toluene / 16 h / Heating 2: 39 percent / tetrakis(triphenylphosphine)palladium(0) / toluene / 3 h / Heating View Scheme

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) → 8-cyclopentyl-6-(1-ethoxyvinyl)-5-methyl-2-(3,4,5,6-tetrahydro-2H-[1,3']bipyridinyl-6'-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one (571189-83-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 27 percent / toluene / 16 h / Heating 2: 59 percent / tetrakis(triphenylphosphine)palladium(0) / toluene / 2 h / Heating View Scheme

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) → 8-cyclopentyl-6-(1-ethoxyvinyl)-5-methyl-2-[5-(4-methylpiperazin-1-yl)pyridin-2-ylamino]-8H-pyrido[2,3-d]pyrimidin-7-one (571189-50-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 29 percent / toluene / 4 h / Heating 2: 91 percent / tetrakis(triphenylphosphine)palladium(0) / toluene / 12 h / 110 °C View Scheme

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) → 2-{5-[bis-(2-methoxy-ethyl)-amino]-pyridin-2-ylamino}-8-cyclopentyl-6-(1-ethoxy-vinyl)-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / toluene / 5 h / 110 °C 2: palladium tetrakistriphenylphosphine / toluene / 2 h / 110 °C View Scheme

6‑bromo‑8‑cyclopentyl‑5‑methyl‑2‑(methylsulfinyl)pyrido[2,3‑d]pyrimidin‑7(8H)‑one (571188-81-3) → 8-cyclopentyl-6-(1-ethoxyvinyl)-5-methyl-2-(4-hydroxy-3,4,5,6-tetrahydro-2H-[1,3']bipyridinyl-6'-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one (571189-56-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 17 percent / toluene / 4 h / Heating 2: 83 percent / tetrakis(triphenylphosphine)palladium(0) / toluene / 12 h / 110 °C View Scheme

Upstream product

• 5751-20-2 2-Methylthiouracil 
• 81560-03-4 2-methylsulfanyl-5-bromopyrimidin-4-one 
• 63810-78-6 4?chloro?5?bromo?2?(methylthio)pyrimidine 
• 362656-25-5 6-bromo-8-cyclopentyl-5-methyl-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one 
• 362656-23-3 8?cyclopentyl?5?methyl?2?(methylthio)pyrido[2,3?d]pyrimidin?7(8H)?one 
• 362656-11-9 1-(4-cyclopentylamino-2-methylsulfanylpyrimidin-5-yl)ethanone 
• 362656-31-3 1-(4-cyclopentylamino-2-methylsulfanylpyrimidin-5-yl)ethanol 
• 733039-23-1 5?bromo?N?cyclopentyl?2?(methylthio)pyrimidin?4?amine 
• 49844-90-8 4-Chloro-2-methylthiopyrimidine 
• 1065075-68-4 4-(cyclopentylamino)-2-(methylthio)pyrimidine-5-carboxylic acid 
• 211245-63-5 [4-cyclopentylamino-2-(methylsulfanyl)pyrimidine-5-yl]methanol 
• 211245-62-4 4-cyclopentylamino-2-(methylsulfanyl)pyrimidine-5-carboxylic acid ethyl ester 
• 211245-64-6 4-cyclopentylamino-2-methylsulfanyl-pyrimidine-5-carbaldehyde 
• 1003-03-8 Cyclopentamine 

Downstream Products

• 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 
• 571190-14-2 6-bromo-8-cyclopentyl-2-(4-methoxybenzylamino)-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one 
• 850629-01-5 4-[4-(8-cyclopentyl-5-methyl-7-oxo-6-trimethylsilanylethynyl-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)phenyl]-piperazine-1-carboxylic acid tert-butyl ester 
• 850629-04-8 2-[4-(4-tert-butoxycarbonylpiperazin-1-yl)phenylamino]-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester 
• 850629-06-0 2-[4-(4-tert-butoxycarbonylpiperazin-1-yl)phenylamino]-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid 
• 850629-02-6 4-[4-(8-cyclopentyl-6-ethynyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)phenyl]-piperazine-1-carboxylic acid tert-butyl ester 
• 850629-05-9 2-[4-(4-tert-butoxycarbonylpiperazin-1-yl)phenylamino]-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid methyl ester 
• 850629-03-7 4-[4-(8-cyclopentyl-6-ethyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)phenyl]-piperazine-1-carboxylic acid tert-butyl ester 
• 571189-10-1 4-{6-[8-cyclopentyl-6-(1-ethoxyvinyl)-5-methyl-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 
• 362656-71-1 4-[4-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)phenyl]-piperazine-1-carboxylic acid tert-butyl ester 

Relevant articles and documents

PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONES AS CDK INHIBITORS

The pyrido[2,3-d]pyrimidin-7(8H)-ones of Formula (1) and pharmaceutical compositions containing compounds of Formula (1) as CDK inhibitors are disclosed herein. Methods and use of a compound of Formula 1 in the treatment of cancer and manufacture are also disclosed.

A new route for the synthesis of Palbociclib

Abstract: In this paper, a novel synthetic method for Palbociclib was reported. It was synthesized in eight steps from 2-(methylthio) pyrimidin-4-(3H)-one with approximately 10% overall yield. This protocol started material 2-(methylthio) pyrimidin-4-(3H)-one, involved nucleophilic substitution by thionyl chloride, bromination, nucleophilic substitution by cyclopentylamine, a one pot-two step method (Heck reaction, ring close sequence), oxidation and bromination, cross-coupling reaction, Heck reaction, aqueous workup to afford Palbociclib. This synthetic route used inexpensive raw material and reagents, involved readily controllable reaction conditions and reduced environmental hazards. Graphic abstract: Synthesis of Palbociclib, a small molecule CDK inhibitor, starting from 2-(methylthio) pyrimidin-4-(3H)-one by 8 steps reaction. This method afforded the Palbociclib in 10% yield. [Figure not available: see fulltext.].

A Palumbo vial preparation method of the key intermediate (by machine translation)

The invention discloses a Palumbo Xilin key intermediate 6 - bromo - 2 - methyl sulfonyl - 8 - cyclopentyl - 5 - methyl pyridine and (2, 3 - d) pyrimidine - 7 (8 H) - ketone. The method uses the thiourea pyrimidine as the starting material, by methylation, chloro, bromo synthesis of 5 - bromo - 4 - chloro - 2 - methylthio-pyrimidine, then with the cyclopentamine alkylation, with 2 - butenoic acid by the heck reaction, then the intramolecular acylation reaction for the synthesis of 2 - methylthio - 8 - cyclopentyl - 5 - methyl pyridine and (2, 3 - d) pyrimidine - 7 (8 H) - one, finally with the NBS reaction for the preparation of 6 - bromo - 2 - methyl sulfonyl - 8 - cyclopentyl - 5 - methyl pyridine and (2, 3 - d) pyrimidine - 7 (8 H) - one. The preparation process of the present invention short step, not using the dangerous process, simple and convenient operation, low cost of raw materials, to meet the using requirements of the people. (by machine translation)