LOXO-101 (sulfate)

Base Information

• Chemical Name: LOXO-101 (sulfate)
• CAS No.: 1223405-08-0
• Molecular Formula: C21H22F2N6O2.H2SO4
• Molecular Weight: 526.521
• Mol file: 1223405-08-0.mol

Synonyms:LOXO-101 (sulfate);(3S)-N-[5-[(2R)-2-(2,5-Difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxy-1-pyrrolidinecarboxamide sulfate (1:1)

Chemical Property of LOXO-101 (sulfate)

Chemical Property:

• Appearance/Colour: Light yellow to brown solid
• PSA: 168.98000
• LogP: 3.45140
• Solubility.: ≥18.47 mg/mL in DMSO; ≥2.14 mg/mL in EtOH; ≥29.65 mg/mL in H2O

Purity/Quality:

99%MIN ^*data from raw suppliers

LarotrectinibSulfate ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: LOXO-101 (sulfate) is an orally bioavailable, potent, ATP-competitive inhibitor of TRKA, TRKB, and TRKC. LOXO-101 has IC50 values in the low nanomolar range for inhibition of all three TRK family members in binding and cellular assays, with 100x selectivity over other kinases, and has shown acceptable pharmaceutical properties and safety in nonclinical models. The TRK family of neurotrophin receptors, TRKA, TRKB, and TRKC (encoded by NTRK1, NTRK2, and NTRK3 genes, respectively) and their neurotrophin ligands regulate growth, differentiation and survival of neurons.
• Uses: Larotrectinib Sulfate is a potent and selective oral ATP-competitive inhibitor of tropomyosin receptor kinases (TRK).

Technology Process of LOXO-101 (sulfate)

There total 11 articles about LOXO-101 (sulfate) 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: 98.43%

(3S)-N-[5-[(2R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidi n-3-yl]-3-hydroxypyrrolidine-1-carboxamide (1223403-58-4) → (S)-N-(5-((R)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate (1223405-08-0)

Guidance literature:

With sulfuric acid; In methanol; at 20 ℃; for 0.5h; Solvent; Concentration; Temperature; Inert atmosphere;

Reference yield:

phenyl (5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3,3a-dihydropyrazolo[1,5-a]pyrimidin-3-yl)carbamate (2135871-21-3) + 3-hydroxypyrrolidine (100243-39-8) → (S)-N-(5-((R)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate (1223405-08-0)

Guidance literature:

phenyl (5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3,3a-dihydropyrazolo[1,5-a]pyrimidin-3-yl)carbamate; 3-hydroxypyrrolidine; In ethanol; water; at 50 ℃; Inert atmosphere;

With sulfuric acid; In ethanol; n-heptane; water; at 30 ℃; Inert atmosphere;

Reference yield:

5-chloro-3-nitropyrazolo[1,5-a]pyrimidine (1363380-51-1) → (S)-N-(5-((R)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate (1223405-08-0)

Guidance literature:

Multi-step reaction with 4 steps

1.1: triethylamine / tetrahydrofuran; ethanol / 40 - 50 °C / Inert atmosphere

2.1: zinc; hydrogenchloride / tetrahydrofuran; water / 5 - 30 °C / Inert atmosphere

3.1: potassium carbonate / water / 20 - 30 °C / Inert atmosphere

4.1: water; ethanol / 50 °C / Inert atmosphere

4.2: 30 °C / Inert atmosphere

With hydrogenchloride; potassium carbonate; triethylamine; zinc; In tetrahydrofuran; ethanol; water;

upstream raw materials:

(3S)-N-[5-[(2R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidi n-3-yl]-3-hydroxypyrrolidine-1-carboxamide

phenyl (5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3,3a-dihydropyrazolo[1,5-a]pyrimidin-3-yl)carbamate

3-hydroxypyrrolidine

5-chloro-3-nitropyrazolo[1,5-a]pyrimidine

Refernces

• 1、 -. "METHODS OF TREATING PEDIATRIC CANCERS". Paragraph 0382; 0419; 0420; 0421; 0422. . Retrieved 2017/10/18.