TPX-0005

Base Information

• Chemical Name: TPX-0005
• CAS No.: 1802220-02-5
• Molecular Formula: C₁₈H₁₈FN₅O₂
• Molecular Weight: 355.372
• Mol file: 1802220-02-5.mol

Synonyms:

Chemical Property of TPX-0005

Chemical Property:

• PKA: 10.79±0.60(Predicted)
• Density: 1.46±0.1 g/cm3(Predicted)

Purity/Quality:

99% ^*data from raw suppliers

Repotrectinib(TPX-005) >98% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Description: Ropotrectinib (TPX-0005; TP Therapeutics, San Diego, CA, USA) is a nextgeneration ROS1 inhibitor, a novel three-dimensional macrocyle with a much smaller size (MW <370) than current ROS1 inhibitors. It was specifically designed to overcome resistance mutations. Preclinical studies have shown activity against gatekeeper and solvent mutations, including G2032R, D2033N, L2026M, S1986F/Y, L1951R, and kinases involved in bypass signaling such as focal adhesion kinase, SRC proto-oncogene, and non-receptor tyrosine kinase [102, 103].

Technology Process of TPX-0005

There total 21 articles about TPX-0005 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: 88.5%

5-(((R)-1-(2-(((S)-1-aminopropan-2-yl)oxy)-5-fluorophenyl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid hydrochloride → repotrectinib (1802220-02-5)

Guidance literature:

With pentafluorophenyl diphenyl-phosphinate; N-ethyl-N,N-diisopropylamine; In dichloromethane; N,N-dimethyl-formamide; for 1h; Concentration;

Reference yield: 43.49%

5-(((R)-1-(2-(((S)-1-((tert-butoxycarbonyl)amino)prop-2-yl)oxy)-5-fluorophenyl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid ethyl ester → repotrectinib (1802220-02-5)

Guidance literature:

5-(((R)-1-(2-(((S)-1-((tert-butoxycarbonyl)amino)prop-2-yl)oxy)-5-fluorophenyl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid ethyl ester; With water; lithium hydroxide; In tetrahydrofuran; methanol; at 70 ℃; for 2h;

With hydrogenchloride; In 1,4-dioxane; at 20 ℃; for 3h;

With pentafluorophenyl diphenyl-phosphinate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20 ℃; for 2.5h;

Reference yield:

5-chloropyrazolo[1,5-a]pyrimidine-3-carboxylic acid ethyl ester (1224944-77-7) → repotrectinib (1802220-02-5)

Guidance literature:

Multi-step reaction with 4 steps

1: N-ethyl-N,N-diisopropylamine / butan-1-ol / 5 h / 25 - 120 °C

2: lithium hydroxide; water / tetrahydrofuran; methanol / 70 °C

3: hydrogenchloride / dichloromethane; 1,4-dioxane / 2 h / 20 °C

4: N-ethyl-N,N-diisopropylamine; pentafluorophenyl diphenyl-phosphinate / N,N-dimethyl-formamide; dichloromethane / 1 h

With hydrogenchloride; pentafluorophenyl diphenyl-phosphinate; water; N-ethyl-N,N-diisopropylamine; lithium hydroxide; In tetrahydrofuran; 1,4-dioxane; methanol; dichloromethane; N,N-dimethyl-formamide; butan-1-ol;

upstream raw materials:

5-chloropyrazolo[1,5-a]pyrimidine-3-carboxylic acid ethyl ester

(R)-2-(1-aminoethyl)-4-fluorophenol hydrochloride

2,5-difluorobenzonitrile

Refernces

• 1、 -. "DIARYL MACROCYCLE POLYMORPH". . . Retrieved 2017/01/26.
• 2、 -. "DIARYL MACROCYCLES AS MODULATORS OF PROTEIN KINASES". . . Retrieved 2015/11/27.