LOXO-101

Base Information

• Chemical Name: LOXO-101
• CAS No.: 1223403-58-4
• Molecular Formula: C21H22F2N6O2
• Molecular Weight: 428.441
• Mol file: 1223403-58-4.mol

Synonyms:LOXO-101;(R)-N-(5-((S)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide;(3S)-N-[5-[(2R)-2-(2,5-Difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxy-1-pyrrolidinecarboxamide;ARRY 470;Larotrectinib

Chemical Property of LOXO-101

Chemical Property:

• Appearance/Colour: White to yellow solid
• PKA: 8.41±0.40(Predicted)
• PSA: 86.00000
• Density: 1.55±0.1 g/cm3(Predicted)
• LogP: 3.02340
• Storage Temp.: RT
• Solubility.: Soluble in DMSO (up to 5 mg/ml).

Purity/Quality:

98%min ^*data from raw suppliers

Larotrectinib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Description: Larotrectinib (VITRAKVIR) is an orally administered, small molecule, highly-selective, tropomyosin receptor kinase (TRK) inhibitor that was developed by Loxo Oncology in collaboration with Bayer AG as a treatment for adult and paediatric patients whose cancers harbour neurotrophic receptor tyrosine kinase (NTRK) gene fusions.? Larotrectinib is a highly selective, potent inhibitor of TRKA, TRKB and TRKC (in vitro 50% inhibitory constant 5–11 nmol/L), with minimal or no activity against other kinase and non-kinase targets [1, 2]. Inhibition of TRKs prevents TRK activation, resulting in both the induction of cellular apoptosis and the inhibition of cell growth in tumours that overexpress TRKs. LOXO-101 is an inhibitor of the tropomyosin-related kinases TrkA, TrkB, and TrkC (IC50s = 2-20 nM). It is selective for TrkA, -B, and -C over a panel of 226 kinases at 1 μM. LOXO-101 inhibits the growth of CUTO-3.29, KM12, and MO-91 patient-derived cancer cell lines (IC50s = <100, <10, and <10 nM, respectively). In vivo, LOXO-101 (60 and 200 mg/kg) reduces tumor growth in a KM12 mouse xenograft model.
• Uses: LOXO-101 is a drug used to treat adults and children with certain types of solid tumors that have spread or cannot be removed by surgery and have the?NTRK?gene fusion. It is also being studied in the treatment of other types of cancer. Larotrectinib is a TRK Inhibitor (Tyrosine kinase inhibitor).

Technology Process of LOXO-101

There total 17 articles about LOXO-101 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: 95.0%

C21H20F2N6O2 → (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)

Guidance literature:

With zinc(II) tetrahydroborate; In 2-methyltetrahydrofuran; at 50 - 60 ℃; for 3h; Solvent; Reagent/catalyst;

Reference yield: 91.0%

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) → (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)

Guidance literature:

With triethylamine; In tetrahydrofuran; at 75 ℃; for 6h;

Reference yield: 91.0%

5-[(2R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-amine (1223404-88-3) + 3-hydroxypyrrolidine (100243-39-8) + 1,1'-carbonyldiimidazole (530-62-1) → (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)

Guidance literature:

5-[(2R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-amine; 1,1'-carbonyldiimidazole; In dichloromethane; at 20 ℃; for 2h;

3-hydroxypyrrolidine; In dichloromethane; for 0.0833333h;

upstream raw materials:

5-[(2R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-amine

3-hydroxypyrrolidine

1,1'-carbonyldiimidazole

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

Downstream raw materials:

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