(1R)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-[4-methyl-2-(1-methylethyl)-3-pyridinyl]-4-[(2S)-2-methyl-4-(1-oxo-2-propen-1-yl)-1-piperazinyl]pyrido[2,3-d]pyrimidin-2(1H)-one

Base Information

• Chemical Name: (1R)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-[4-methyl-2-(1-methylethyl)-3-pyridinyl]-4-[(2S)-2-methyl-4-(1-oxo-2-propen-1-yl)-1-piperazinyl]pyrido[2,3-d]pyrimidin-2(1H)-one
• CAS No.: 2296729-00-3
• Molecular Formula: C₃₀H₃₀F₂N₆O₃
• Molecular Weight: 560.603
• Mol file: 2296729-00-3.mol

Synonyms:

Chemical Property of (1R)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-[4-methyl-2-(1-methylethyl)-3-pyridinyl]-4-[(2S)-2-methyl-4-(1-oxo-2-propen-1-yl)-1-piperazinyl]pyrido[2,3-d]pyrimidin-2(1H)-one

Chemical Property:

• Boiling Point: 730.5±70.0 °C(Predicted)
• Density: 1.36±0.1 g/cm3(Predicted)

Purity/Quality:

98%min ^*data from raw suppliers

AMG-510(Sotorasib) >99%,chiralpurity>99% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Description: Sotorasib (AMG510) is a chiral compound and a potent KRAS G12C covalent inhibitor with potential antitumor activity.
• Uses: Sotorasib (AMG510) is the first KRAS (G12C) inhibitor to enter clinical development. Having shown antitumor activity in clinical trials, AMG 510 represents a potentially transformative therapy.

Technology Process of (1R)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-[4-methyl-2-(1-methylethyl)-3-pyridinyl]-4-[(2S)-2-methyl-4-(1-oxo-2-propen-1-yl)-1-piperazinyl]pyrido[2,3-d]pyrimidin-2(1H)-one

There total 29 articles about (1R)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-[4-methyl-2-(1-methylethyl)-3-pyridinyl]-4-[(2S)-2-methyl-4-(1-oxo-2-propen-1-yl)-1-piperazinyl]pyrido[2,3-d]pyrimidin-2(1H)-one which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 80.0%

6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-4-[(2S)-2-methylpiperazin-1-yl]-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]pyrido[2,3-d]pyrimidin-2(1H)-one + acryloyl chloride (814-68-6,25189-84-8) → (1R)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-[4-methyl-2-(1-methylethyl)-3-pyridinyl]-4-[(2S)-2-methyl-4-(1-oxo-2-propen-1-yl)-1-piperazinyl]pyrido[2,3-d]pyrimidin-2(1H)-one (2252403-56-6,2296729-00-3)

Guidance literature:

In 1-methyl-pyrrolidin-2-one; at 20 - 30 ℃; for 2h;

Reference yield:

2,6-dichloro-5-fluoro-3-pyridinecarboxylic acid (82671-06-5) → (1R)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-[4-methyl-2-(1-methylethyl)-3-pyridinyl]-4-[(2S)-2-methyl-4-(1-oxo-2-propen-1-yl)-1-piperazinyl]pyrido[2,3-d]pyrimidin-2(1H)-one (2252403-56-6,2296729-00-3)

Guidance literature:

Multi-step reaction with 7 steps

1.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 20 °C

1.2: 0.5 h / 0 °C

2.1: tetrahydrofuran; dichloromethane / 1 h / 75 °C

2.2: 1 h / 0 °C

3.1: potassium hexamethylsilazane / tetrahydrofuran / 0.67 h / 20 °C / Cooling with ice

4.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / acetonitrile / 1 h / 80 °C

5.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 1 h / 20 °C / Cooling with ice

6.1: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / water; 1,4-dioxane / 1 h / 90 °C / Inert atmosphere

7.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C

7.2: 0.17 h / 0 °C

With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; oxalyl dichloride; potassium acetate; potassium hexamethylsilazane; N-ethyl-N,N-diisopropylamine; N,N-dimethyl-formamide; trifluoroacetic acid; trichlorophosphate; In tetrahydrofuran; 1,4-dioxane; dichloromethane; water; acetonitrile;

Reference yield:

(3S)-4-(6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(2-isopropyl-4-methylpyridin-3-yl)-2-oxo-1,2-dihydropyrido[2,3-d]pyrimidin-4-yl)-3-methylpiperazin-1-carboxylic acid tert-butyl ester + acryloyl chloride (814-68-6,25189-84-8) → (1R)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-[4-methyl-2-(1-methylethyl)-3-pyridinyl]-4-[(2S)-2-methyl-4-(1-oxo-2-propen-1-yl)-1-piperazinyl]pyrido[2,3-d]pyrimidin-2(1H)-one (2252403-56-6,2296729-00-3)

Guidance literature:

(3S)-4-(6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(2-isopropyl-4-methylpyridin-3-yl)-2-oxo-1,2-dihydropyrido[2,3-d]pyrimidin-4-yl)-3-methylpiperazin-1-carboxylic acid tert-butyl ester; With trifluoroacetic acid; In dichloromethane; at 20 ℃; for 1h;

acryloyl chloride; With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 ℃; for 0.166667h;

upstream raw materials:

3-amino-2-bromo-4-methylpyridine

4-methyl-2-(1-methylethyl)-3-pyridinamine

2,6-dichloro-5-fluoro-3-pyridinecarboxylic acid

2,6-dichloro-5-fluoropyridine-3-carboxamide

Refernces

• 1、 -. "IMPROVED SYNTHESIS OF KRAS G12C INHIBITOR COMPOUND". . . Retrieved 2021/05/21.
• 2、 -. "COMBINATION THERAPY INCLUDING A KRASG12C INHIBITOR AND ONE OR MORE ADDITIONAL PHARMACEUTICALLY ACTIVE AGENTS FOR THE TREATMENT OF CANCERS". . . Retrieved 2020/06/10.