1229236-86-5

Basic information

• Product Name: LY 2784544
• Synonyms: LY 2784544;3-[(4-Chloro-2-fluorophenyl)methyl]-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(4-morpholinylmethyl)imidazo[1,2-b]pyridazin-6-amine;3-(4-chloro-2-fluorobenzyl)-2-Methyl-N-(3-Methyl-1H-pyrazol-5-yl)-8-(MorpholinoMethyl)iMidazo[1,2-b]pyridazin-6-aMine;LY2784544/LY-2784544;IMidazo[1,2-b]pyridazin-6-aMine, 3-[(4-chloro-2-fluorophenyl)Methyl]-2-Methyl-N-(5-Methyl-1H-pyrazol-3-yl)-8-(4-MorpholinylMethyl)-;LY2874544;Gandotinib (LY2784544);3-[(4-Chloro-2-fluorophenyl)methyl]-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(4-morpholinylmethyl)imidazo[1,2-b]pyridazin-6-amine LY 2784544
• CAS NO: 1229236-86-5
• Molecular Formula: C₂₃H₂₅ClFN₇O
• Molecular Weight: 469.95
• EINECS: -0
• Product Categories: Inhibitor;JAK/STAT;Inhibitors;JAK;STAT
• Mol File: 1229236-86-5.mol

Chemical Properties

• Appearance: /
• Density: 1.45
• Solubility: ≥23.5 mg/mL in DMSO; insoluble in H2O; ≥5.65 mg/mL in EtOH with gentle warming and ultrasonic
• PKA: 14.12±0.10(Predicted)
• CAS DataBase Reference: LY 2784544(CAS DataBase Reference)
• NIST Chemistry Reference: LY 2784544(1229236-86-5)
• EPA Substance Registry System: LY 2784544(1229236-86-5)

Safety Data

• Hazardous Substances Data: 1229236-86-5(Hazardous Substances Data)

Usage

Uses

Used in Oncology:
LY 2784544 is used as a potential treatment for patients with myeloproliferative neoplasm, a group of blood cancers that involve the overproduction of certain types of blood cells. By inhibiting the JAK2 enzyme, LY 2784544 may help to regulate the abnormal cell signaling that contributes to the development and progression of these cancers.

Upstream product

• 175711-83-8 4’-chloro-2’-fluoroacetophenone 
• 1229236-80-9 (4-chloro-2-fluorophenyl)(6-chloro-2-methylimidazo-[1,2-b]pyridazin-3-yl)methanone 
• 1346221-91-7 N-(1-tert-butyl-3-methyl-1H-pyrazol-5-yl)-3-(4-chloro-2-fluorobenzyl)-2-methyl-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine 
• 1229236-83-2 (4-chloro-2-fluorophenyl)(6-chloro-2-methyl-8-(morpholino-methyl)imidazo[1,2-b]pyridazin-3-yl)methanone 
• 1229236-79-6 (E)-N'-(6-chloropyridazin-3-yl)-N,N-dimethylacetimidamide 
• 1229236-85-4 4-((6-chloro-3-(4-chloro-2-fluorobenzyl)-2-methylimidazo-[1,2-b]pyridazin-8-yl)methyl)morpholine 
• 31230-17-8 3-amino-5-methylpyrazole 

Downstream Products

• 1229236-87-6 3-(4-chloro-2-fluorobenzyl)-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine hydrochloride 

Relevant articles and documents

Development and a practical synthesis of the JAK2 inhibitor LY2784544

The route selection and process research and development of a practical synthesis for JAK2 inhibitor LY2784544 is described. The first-generation synthesis route, similar to that used in discovery for derivatization of a benzylic amine moiety, was 14 overall steps and possessed several steps that required extensive development for large-scale production. Route selection considerations led to a modified synthesis that utilized a novel vanadium-catalyzed carbon-carbon bond-forming arylation reaction for incorporation of the key benzylic morpholine moiety. A protecting group used to mask an amino pyrazole unit was modified from PMB to tert-butyl, resulting in a dramatic reduction in the overall length of the route. These two major changes resulted in an eight-step synthesis, which was six steps shorter than the first-generation synthesis. In the pilot plant, the new synthesis was scaled to produce >100 kg of LY2784544 in high yield and purity under GMP conditions. The overall development including the vanadium-catalyzed C-C bond-forming methodology, a ketone reductive deoxygenation, and a palladium-catalyzed amination is described.

AMINO PYRAZOLE COMPOUND

The present invention provides amino pyrazole compounds useful in the treatment of chronic myeloproliferative disorders and various cancers, e.g., glioblastoma, breast cancer, multiple myeloma, prostate cancer, and leukemias.