IPI 145

Base Information

• Chemical Name: IPI 145
• CAS No.: 1201438-56-3
• Molecular Formula: C22H17ClN6O
• Molecular Weight: 416.87
• Mol file: 1201438-56-3.mol

Synonyms: Duvelisib, 1201438-56-3, Duvelisib [USAN], SureCN153543, UNII-610V23S0JI, IPI145, CHEMBL3039502, MolPort-028-600-025

Chemical Property of IPI 145

Chemical Property:

• Boiling Point: 757.8±60.0 °C(Predicted)
• PKA: 10.05±0.10(Predicted)
• PSA: 88.49000
• Density: 1.474±0.06 g/cm3(Predicted)
• LogP: 4.55650
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (up to at least 25 mg/ml)

Purity/Quality:

98% ^*data from raw suppliers

IPI-145 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Duvelisib (1201438-56-3) is a potent and selective (IC50’s: PI3Kα = 1602nM, PI3Kβ = 85nM, PI3Kδ= 2.5nM, PI3Kγ = 27nM) dual PI3Kδ/γ inhibitor.1 It inhibits B and T cell proliferation, blocks neutrophil migration, and inhibits basophil activation. Duvelisib antagonizes B-cell receptor cross-linking activated pro-survival signals in primary chronic lymphocytic leukemia cells.2?Duvelisib also shows preclinical/clinical activity against other hematologic malignancies such as Non-Hodgkins lymphoma, T-cell lymphoma, and others.3,4?Useful clinical agent for the treatment of various blood cancers. Low-dose treatment of T-cell-inflamed tumor models of head and neck cancers with Duvelisib enhanced responses to PD-L1 blockade via suppression of myeloid-derived suppressor cells.5?Higher doses reversed the effect due to suppression of tumor-infiltrating T lymphocytes
• Uses: IPI 145 is an 1,2-dihydroisoquinolin-1(2H)-one derivative and has been developed as a modulator of PI3 kinase.

Technology Process of IPI 145

There total 8 articles about IPI 145 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: 93.5%

8-chloro-2-phenyl-3-((1S)-1-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-ylamino)ethyl)isoquinolin-1(2H)-one (1350643-73-0) → (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one (1201438-56-3)

Guidance literature:

8-chloro-2-phenyl-3-((1S)-1-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-ylamino)ethyl)isoquinolin-1(2H)-one; With hydrogenchloride; In ethanol; water; at 22 - 35 ℃; for 1.5h;

With ammonium hydroxide; In ethanol; water; pH=8 - 9; Product distribution / selectivity;

Reference yield:

2-chloro-6-methylbenzoic acid (21327-86-6) → (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one (1201438-56-3)

Guidance literature:

Multi-step reaction with 4 steps

1.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C

1.2: 2 h / 20 - 40 °C

2.1: n-butyllithium / hexane; tetrahydrofuran / 1 h / -30 - -10 °C / Inert atmosphere

2.2: 1 h / -30 - -10 °C / Inert atmosphere

2.3: 1 h / Reflux

3.1: triethylamine / butan-1-ol / 16 h / Reflux

4.1: hydrogenchloride; water / ethanol / 1 h / 20 °C

4.2: pH 8 - 9

With hydrogenchloride; n-butyllithium; oxalyl dichloride; water; triethylamine; N,N-dimethyl-formamide; In tetrahydrofuran; ethanol; hexane; dichloromethane; butan-1-ol;

Reference yield:

2-chloro-6-methyl-N-phenylbenzamide (1386861-46-6) → (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one (1201438-56-3)

Guidance literature:

Multi-step reaction with 3 steps

1.1: n-butyllithium / hexane; tetrahydrofuran / 1 h / -30 - -10 °C / Inert atmosphere

1.2: 1 h / -30 - -10 °C / Inert atmosphere

1.3: 1 h / Reflux

2.1: triethylamine / butan-1-ol / 16 h / Reflux

3.1: hydrogenchloride; water / ethanol / 1 h / 20 °C

3.2: pH 8 - 9

With hydrogenchloride; n-butyllithium; water; triethylamine; In tetrahydrofuran; ethanol; hexane; butan-1-ol;

upstream raw materials:

aniline

2-chloro-6-methylbenzoic acid

(S)-3-(1-aminoethyl)-8-chloro-2-phenylisoquinoline-1(2H)-one

8-chloro-2-phenyl-3-((1S)-1-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-ylamino)ethyl)isoquinolin-1(2H)-one

Downstream raw materials:

(S)-3-(1-((9H-purin-6-yl)amino)ethyl)-2-phenyl-8-(pyrrolidin-1-yl)isoquinolin-1(2H)-one

(S)-3-(1-((9H-purin-6-yl)amino)ethyl)-2-phenyl-8-(1H-pyrazol-4-yl)isoquinolin-1(2H)-one

(S)-3-(1-((9H-purin-6-yl)amino)ethyl)-1-oxo-2-phenyl-1,2-dihydroisoquinoline-8-carbaldehyde

(S)-3-(1-((9H-purin-6-yl)amino)ethyl)-1-oxo-2-phenyl-1,2-dihydroisoquinoline-8-carbonitrile

Refernces

• 1、 -. "CHEMICAL COMPOUNDS, COMPOSITIONS AND METHODS FOR KINASE MODULATION". . . Retrieved 2011/12/04.