X-376

Base Information

• Chemical Name: X-376
• CAS No.: 1365267-27-1
• Molecular Formula: C25H25Cl2FN6O3
• Molecular Weight: 547.416
• Mol file: 1365267-27-1.mol

Synonyms:X-376;X-396;6-Amino-5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-N-[4-[(4-methyl-1-piperazinyl)carbonyl]phenyl]-3-pyridazinecarboxamide;Ensartinib

Chemical Property of X-376

Chemical Property:

• Appearance/Colour: White to off-white solid
• Boiling Point: 695.1±55.0 °C(Predicted)
• PKA: 10.70±0.70(Predicted)
• PSA: 113.68000
• Density: 1.428±0.06 g/cm3(Predicted)
• LogP: 4.81460

Purity/Quality:

98.0%~102.0% ^*data from raw suppliers

Ensartinib >98% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Uses: X-376 is an ALK inhibitor with potential efficacy in the treatment of non-small cell lung cancer.

Technology Process of X-376

There total 7 articles about X-376 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: 80.5%

C35H41Cl2FN6O7 (1370651-39-0) → 6-amino-5-[(1{R})-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-{N}-[4-[(3{R},5{S})-3,5-dimethylpiperazine-1-carbonyl]phenyl]pyridazine-3-carboxamide (1365267-27-1)

Guidance literature:

With trifluoroacetic acid; In dichloromethane; at 20 ℃; for 2h;

Reference yield:

2',6'-dichloro-3'-fluoroacetophenone (290835-85-7) → 6-amino-5-[(1{R})-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-{N}-[4-[(3{R},5{S})-3,5-dimethylpiperazine-1-carbonyl]phenyl]pyridazine-3-carboxamide (1365267-27-1)

Guidance literature:

Multi-step reaction with 8 steps

1.1: sodium tetrahydroborate / methanol / 1 h / 0 - 20 °C

1.2: 0 °C / pH 6

2.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-(tert-butoxycarbonyl)-D-proline / 1,2-dichloro-ethane / 0 - 20 °C

3.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C

3.2: Reflux

4.1: dmap / N,N-dimethyl-formamide / 20 °C

5.1: sodium acetate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / N,N-dimethyl-formamide / 90 °C

6.1: water; lithium hydroxide / tetrahydrofuran / 20 °C

6.2: pH 5

7.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 0.5 h / 20 °C

7.2: 0.5 h / 20 °C

8.1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C

With dmap; sodium tetrahydroborate; water; sodium acetate; sodium hydride; N-(tert-butoxycarbonyl)-D-proline; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; HATU; trifluoroacetic acid; lithium hydroxide; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; In tetrahydrofuran; methanol; dichloromethane; 1,2-dichloro-ethane; N,N-dimethyl-formamide;

Reference yield:

1-(2,6-dichloro-3-fluorophenyl)ethanol (756520-66-8) → 6-amino-5-[(1{R})-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-{N}-[4-[(3{R},5{S})-3,5-dimethylpiperazine-1-carbonyl]phenyl]pyridazine-3-carboxamide (1365267-27-1)

Guidance literature:

Multi-step reaction with 7 steps

1.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-(tert-butoxycarbonyl)-D-proline / 1,2-dichloro-ethane / 0 - 20 °C

2.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C

2.2: Reflux

3.1: dmap / N,N-dimethyl-formamide / 20 °C

4.1: sodium acetate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / N,N-dimethyl-formamide / 90 °C

5.1: water; lithium hydroxide / tetrahydrofuran / 20 °C

5.2: pH 5

6.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 0.5 h / 20 °C

6.2: 0.5 h / 20 °C

7.1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C

With dmap; water; sodium acetate; sodium hydride; N-(tert-butoxycarbonyl)-D-proline; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; HATU; trifluoroacetic acid; lithium hydroxide; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; In tetrahydrofuran; dichloromethane; 1,2-dichloro-ethane; N,N-dimethyl-formamide;

upstream raw materials:

1-(2,6-dichloro-3-fluorophenyl)ethanol

2',6'-dichloro-3'-fluoroacetophenone

(R)-1-(2,6-dichloro-3-fluorophenyl)ethan-1-ol

C₁₂H₉Cl₃FN₃O

Refernces