Tamatinib

Base Information

• Chemical Name: Tamatinib
• CAS No.: 841290-80-0
• Molecular Formula: C22H23FN6O5
• Molecular Weight: 470.46
• European Community (EC) Number: 617-533-5
• UNII: RC3A285J2G
• DSSTox Substance ID: DTXSID30458939
• Nikkaji Number: J2.819.266E
• Wikidata: Q27088935
• Pharos Ligand ID: Q44NG3N9YC71
• Metabolomics Workbench ID: 150343
• ChEMBL ID: CHEMBL475251
• Mol file: 841290-80-0.mol

Synonyms:841290-80-0;tamatinib;R-406;R406 (free base);R406 free base;6-(5-fluoro-2-(3,4,5-trimethoxyphenylamino)pyrimidin-4-ylamino)-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one;Tamatinib free base;6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one;R 406;CHEMBL475251;RC3A285J2G;6-({5-Fluoro-2-[(3,4,5-Trimethoxyphenyl)amino]pyrimidin-4-Yl}amino)-2,2-Dimethyl-2h-Pyrido[3,2-B][1,4]oxazin-3(4h)-One;841290-80-0 (free base);6-((5-fluoro-2-((3,4,5-trimethoxyphenyl)amino)pyrimidin-4-yl)amino)-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one;R940406;R406(free base);BDBM50249542;2H-Pyrido(3,2-b)-1,4-oxazin-3(4H)-one, 6-((5-fluoro-2-((3,4,5-trimethoxyphenyl)amino)-4-pyrimidinyl)amino)-2,2-dimethyl-;6-((5-fluoro-2-((3,4,5-trimethoxyphenyl)amino)-4-pyrimidinyl)amino)-2,2-dimethyl-2h-pyrido(3,2-b)-1,4-oxazin-3(4h)-one;6-(5-Fluoro-2-(3,4,5-trimethoxy-phenylamino)-pyrimidin-4-ylamino)-2,2-dimethyl-4H-pyrido(3,2-b)(1,4)oxazin-3-one;6-(5-fluoro-2-(3,4,5-trimethoxyphenylamino)pyrimidin-4-ylamino)-2,2-dimethyl-2H-pyrido[3,2-b];6-[[5-Fluoro-2-[(3,4,5-trimethoxyphenyl)amino]-4-pyrimidinyl]amino]-2,2-dimethyl-2H-pyrido[3,2-b]-1,4-oxazin-3(4H)-one;6-[5-FLUORO-2-(3,4,5-TRIMETHOXY-PHENYLAMINO)-PYRIMIDIN-4-YLAMINO]-2,2-DIMETHYL-4H-PYRIDO[3,2-B][1,4]OXAZIN-3-ONE;3fqs;3piy;Kinome_1211;D0S6TK;UNII-RC3A285J2G;MLS006011151;GTPL5706;SCHEMBL1200144;BDBM60665;CHEBI:91348;AMY9174;DTXSID30458939;EX-A103;NHHQJBCNYHBUSI-UHFFFAOYSA-N;BCPP000094;HMS3265G15;HMS3265G16;HMS3265H15;HMS3265H16;HMS3654F22;BCP01933;MFCD09970820;NSC772498;NSC800858;s1533;AKOS015951111;R406 (freebase) - Adooq Bioscience;CCG-264908;CS-0436;DB07159;NSC-772498;NSC-800858;PB13129;SB16611;NCGC00182051-02;NCGC00182051-03;NCGC00182051-12;NCGC00182051-18;6-[5-Fluoro-2-(3,4,5-trimethoxyphenylamino)pyrimidin-4-ylamino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one;AC-32820;AS-16262;HY-11108;SMR004702925;LS-193799;FT-0650726;SW219254-1;US9145414, R406;J-517971;BRD-K20285085-001-01-4;Q27088935;2H-PYRIDO[3,2-B]-1,4-OXAZIN-3(4H)-ONE,6-[[5-FLUORO-2-[(3,4,5-TRIMETHOXPHENYL)AMINO]-4-PYRIMIDINYL]AMINO]-2,2-DIMETHYL;6-[[5-Fluoro-2-[(3,4,5-trimethoxyphenyl)amino]-4-pyrimidinyl]amino]-2,2-dimethyl-2H-pyrido[3,2-b]-1,4-oxazine-3(4H)-one;6-[[5-fluoro-2-[(3,4,5-trimethoxyphenyl)amino]pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[2,3-e][1,4]oxazin-3-one;6-[5-Fluoro-2-(3,4,5-trimethoxy-phenylamino)-pyrimidin-4-ylamino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one;6-[[5-Fluoro-2-[(3,4,5-trim;6-{[5-Fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino}-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one;6-5-Fluoro-2-(3,4,5-trimethoxyphenylamino)pyrimidin-4-ylamino-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one

Chemical Property of Tamatinib

Chemical Property:

• PKA: 10.63±0.40(Predicted)
• PSA: 128.75000
• Density: 1.358 g/cm³
• LogP: 3.91720
• Storage Temp.: Refrigerator
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• XLogP3: 3.1
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 11
• Rotatable Bond Count: 7
• Exact Mass: 470.17139602
• Heavy Atom Count: 34
• Complexity: 691

Purity/Quality:

96% 1H NMR ^*data from raw suppliers

R 406 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1(C(=O)NC2=C(O1)C=CC(=N2)NC3=NC(=NC=C3F)NC4=CC(=C(C(=C4)OC)OC)OC)C
• Uses: Intermediate used for preparation of prodrugs of pyrimidine-2,4-diamines as anticancer agents. R406 is a potent ATP-competitive inhibitor of spleen tyrosine kinase (Syk, Ki = 30 nM). Through this action, R406 blocks FcεRI-dependent mast cell activation (EC50 = 43 nM) and, at 3 μM, reduces the release of IL-10, -12, and -13 by immune complex-pulsed dendritic cells. R406 is orally available and can reduce immune complex-mediated inflammation. In cancers characterized by over-expression of Syk, R406 can prevent signaling downstream of Syk and induce apoptosis. R406 also inhibits Syk-dependent signaling through c-Jun N-terminal kinase in rheumatoid arthritis synoviocytes, suggesting a therapeutic intervention in this autoimmune disease.[Cayman Chemical]

Technology Process of Tamatinib

There total 4 articles about Tamatinib 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: 91.0%

6-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one (575484-83-2) + 3,4,5-Trimethoxyaniline (24313-88-0) → 6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one (841290-80-0)

Guidance literature:

In 1-methyl-pyrrolidin-2-one; water; at 120 ℃; for 10h; Inert atmosphere; Large scale;

Reference yield: 52.0%

N4-(2,2-dimethyl-4-[(di-tert-butyl-phosphonoxy)methyl]-3-oxo-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine (901119-38-8) → 6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one (841290-80-0) + N4-(2,2-dimethyl-4-[hydroxymethyl]-3-oxo-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine + fostamatinib (901119-35-5)

Guidance literature:

With trifluoroacetic acid; In dichloromethane; at 0 ℃; for 1.58h; Product distribution / selectivity;

Reference yield:

C27H34FN6O9P → 6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one (841290-80-0) + fostamatinib (901119-35-5)

Guidance literature:

With water; acetic acid; at 65 ℃; for 2h; Product distribution / selectivity;

upstream raw materials:

N₄-(2,2-dimethyl-4-[(di-tert-butyl-phosphonoxy)methyl]-3-oxo-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N₂-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine

6-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one

3,4,5-Trimethoxyaniline

Downstream raw materials:

fostamatinib

N₄-(2,2-dimethyl-4-[(di-tert-butyl phosphonoxy)dideuteromethyl]-3-oxo-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N₂-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine

N₄-(2,2-dimethyl-4-[(di-tert-butyl-phosphonoxy)methyl]-3-oxo-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N₂-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine

(+/-)-N₂-(1-chloroethoxycarbonyl)-N₄-(2,2-dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N₂-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine

Refernces

• 1、 -. "PRODRUGS OF 2,4-PYRIMIDINEDIAMINE COMPOUNDS AND THEIR USES". Page/Page column 77-79. . Retrieved 2008/06/13.