Tofacitinib citrate

Base Information

• Chemical Name: Tofacitinib citrate
• CAS No.: 540737-29-9
• Molecular Formula: C16H20N6O·C6H8O7
• Molecular Weight: 504.50
• Hs Code.: 29335990
• European Community (EC) Number: 638-826-4
• UNII: O1FF4DIV0D
• DSSTox Substance ID: DTXSID80202404
• Wikidata: Q27139435
• NCI Thesaurus Code: C95801
• RXCUI: 1358492
• ChEMBL ID: CHEMBL2103743
• Mol file: 540737-29-9.mol

Synonyms:CP 690,550;CP 690550;CP-690,550;CP-690550;CP690550;tasocitinib;tofacitinib;tofacitinib citrate;Xeljanz

Chemical Property of Tofacitinib citrate

Chemical Property:

• Melting Point: 201 °C (decomp)
• Boiling Point: 585.8 °C at 760 mmHg
• Flash Point: 308.1 °C
• PSA: 221.04000
• LogP: 0.23418
• Storage Temp.: room temp
• Solubility.: DMSO: soluble5mg/mL (clear solution; warmed)
• Hydrogen Bond Donor Count: 5
• Hydrogen Bond Acceptor Count: 12
• Rotatable Bond Count: 8
• Exact Mass: 504.19686187
• Heavy Atom Count: 36
• Complexity: 716

Purity/Quality:

98%, ^*data from raw suppliers

CP-690550 Citrate ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1CCN(CC1N(C)C2=NC=NC3=C2C=CN3)C(=O)CC#N.C(C(=O)O)C(CC(=O)O)(C(=O)O)O
• Isomeric SMILES: C[C@@H]1CCN(C[C@@H]1N(C)C2=NC=NC3=C2C=CN3)C(=O)CC#N.C(C(=O)O)C(CC(=O)O)(C(=O)O)O
• Recent ClinicalTrials: Efficacy and Safety Clinical Study of VC005 Tablets in Subjects With Active Ankylosing Spondylitis.
• Recent EU Clinical Trials: A Randomised Pilot Study of the Safety and Efficacy of Tofacitinib (Xeljanz) in Improving Endoscopic Outcomes in Subjects with Ulcerative Colitis with Active, Chronic, Antibiotic Dependent or Refractory Idiopathic Pouchitis
• Description: Tofacitinib citrate is a king of drugs developed by the US pharmaceutical company Pfizer for treating rheumatoid arthritis, trade name Xeljanz, for the treatment of methotrexate inadequate response or intolerance to severe active rheumatoid arthritis (RA) in adult patients. This product is a Janus kinase inhibitor, administered twice daily. November 6, 2012, the US Food and Drug Administration (FDA) and Pfizer jointly announced Tofacitinib citrate is approved for the treatment of methotrexate inadequate response or intolerance to severe active rheumatoid joints arthritis (RA) in adult patients. Xeljanz can be used as monotherapy or in combination with methotrexate or other non-biological disease-modifying antirheumatic drugs (the DMARD) in combination. This medicine should not be in combination with biological DMARD or strong immunosuppressants (such as cyclosporine and azathioprine). Xeljanz is approved by the daily dose of 2 times, each time 5mg. Seven clinical trials evaluated the safety and efficacy of Tofacitinib citrate in moderate to severe active RA in adult patients. In all tests, compared with patients receiving placebo, patients receiving Xeljanz treatment showed significant improvement in clinical response and physical function. In Clinical trials, the most common adverse events were upper respiratory tract infection, headache, diarrhea, nasal congestion, sore throat, and nasopharyngitis. Using Xeljanz was associated with an increased risk of serious infections, including opportunistic infections, tuberculosis, cancer and lymphoma. Xeljanz product label attaches boxed warning on these security risks. Xeljanz treatment is also associated with reducing blood cell counts and increasing cholesterol and liver enzyme values. In order to study Xeljanz long-term impact on heart disease, cancer and severe infections, FDA requires for a post-marketing study, which will evaluate two doses of Xeljanz (Tofacitinib citrate) therapy, and accept a integration of another group of patients approved by the treatment as a control.
• Uses: Tofacitinib citrate has been used:as a ligand for human serum albumin in fluorescence quenching, dynamic light scattering (DLS) measurements, differential scanning calorimetry and molecular docking studiesas a medium supplement for full depth articular cartilage (FDC) explants to monitor cytokine-induced proteoglycan lossas a Janus kinase inhibitor in MCF7 breast cancer cells
• Clinical Use: Potent, selective inhibitor of the Janus kinase family: Treatment of moderate to severe active rheumatoid arthritis
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: concentration of tofacitinib reduced by rifampicin - avoid. Antifungals: concentration of tofacitinib increased by fluconazole and ketoconazole - adjust tofacitinib dose. Antipsychotics: increased risk of agranulocytosis with clozapine - avoid. Ciclosporin: concentration of tofacitinib reduced - avoid. Tacrolimus: concentration of tofacitinib reduced - avoid. Vaccines: risk of generalised infections with live vaccines - avoid.ccccccc

Technology Process of Tofacitinib citrate

There total 89 articles about Tofacitinib citrate 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: 100.0%

3-{(3R,4R)-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile acetate + citric acid (77-92-9,906507-37-7) → tofacitinib citrate (540737-29-9)

Guidance literature:

In methanol; Product distribution / selectivity; Reflux;

Reference yield: 98.5%

tasocitinib (1259404-17-5) + citric acid (77-92-9,906507-37-7) → Tofacitinib citrate (540737-29-9)

Guidance literature:

In ethanol; water; at 75 - 85 ℃; for 0.5h;

Reference yield: 97.0%

3-[(3R,4R)-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]piperidin-1-yl]-3-oxopropionitrile hydrochloride + sodium dihydrogencitrate (18996-35-5) → tofacitinib citrate (540737-29-9)

Guidance literature:

In water; acetonitrile; at 23 - 25 ℃; for 16h; Solvent;

upstream raw materials:

(3R,4R)-methyl-(4-methyl-piperidin-3-yl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

succinimidyl cyanoacetate

citric acid

tert-butyl (3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidine-1-carboxylate

Refernces

• 1、 -. "Synthesis method of tofacitinib citrate". Paragraph 0019; 0032-0033; 0037-0039; 0043-0045; 0049; .... . Retrieved 2021/12/07.
• 2、 -. "Preparation method of tofacitinib citrate". Page/Page column 8-14. . Retrieved 2020/02/14.