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Tofacitinib

Product Name
Tofacitinib
CAS No.
477600-75-2
Chemical Name
Tofacitinib
Synonyms
3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile;Tasocitinib;Tofacitinib base;Tofacitinib (CP-690550,Tasocitinib);Tofactinib;CS-344;CP 690550;Tofatinib;ofacitinib;Tofacitinib
CBNumber
CB0970901
Molecular Formula
C16H20N6O
Formula Weight
312.38
MOL File
477600-75-2.mol
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Tofacitinib Property

Density 
1.3
storage temp. 
-20°C
solubility 
Soluble in DMSO (up to 100 mg/ml) or in Ethanol (up to 100 mg/ml).
form 
Pale powder.
pka
6.04±0.60(Predicted)
color 
Off-white
Stability:
Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
InChI
InChI=1/C16H20N6O/c1-11-5-8-22(14(23)3-6-17)9-13(11)21(2)16-12-4-7-18-15(12)19-10-20-16/h4,7,10-11,13H,3,5,8-9H2,1-2H3,(H,18,19,20)/t11-,13+/s3
InChIKey
UJLAWZDWDVHWOW-BCFRMRSDNA-N
SMILES
N([C@@H]1[C@@H](CCN(C(=O)CC#N)C1)C)(C1N=CN=C2NC=CC=12)C |&1:1,2,r|
CAS DataBase Reference
477600-75-2
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Safety

HS Code 
29335990
Hazardous Substances Data
477600-75-2(Hazardous Substances Data)
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H410Very toxic to aquatic life with long lasting effects

Precautionary statements

P273Avoid release to the environment.

P391Collect spillage. Hazardous to the aquatic environment

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N-Bromosuccinimide Price

Usbiological
Product number
C7905-90
Product name
Tofacitinib
Packaging
25mg
Price
$215
Updated
2021/12/16
Biosynth Carbosynth
Product number
FT32555
Product name
Tofacitinib
Packaging
500mg
Price
$225
Updated
2021/12/16
Activate Scientific
Product number
AS17628-A
Product name
Tofacitinib
Purity
98%
Packaging
1g
Price
$250
Updated
2021/12/16
Biosynth Carbosynth
Product number
FT32555
Product name
Tofacitinib
Packaging
1g
Price
$300
Updated
2021/12/16
ChemScene
Product number
CS-0050
Product name
Tofacitinib
Purity
99.96%
Packaging
1g
Price
$330
Updated
2021/12/16
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Tofacitinib Chemical Properties,Usage,Production

Description

In November 2012, the US FDA approved tofacitinib (also referred to as CP-690550) for the treatment of adult patients with moderate to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate. Tofacitinib is the first small molecule kinase inhibitor approved for the treatment of RA. Tofacitinib is an inhibitor of the four subtypes of Janus kinase (JAK): JAK1, JAK2, JAK3, and Tyk2. The JAKs are intracellular, nonreceptor tyrosine kinases that play important roles in the signal transduction pathway of many cytokines (e.g., interleukins 2, 4, 7, 9, 15, and 21) and are involved in the propagation of inflammation in RA. Tofacitinib acts by inhibiting the phosphorylation and activation of signal transducers and activators of transcription (STATs), thereby suppressing the production of inflammatory mediators in joint tissue. At the enzyme level, tofacitinib inhibits JAKs 1, 2, 3, and Tyk2 with IC50s of 3.2, 4.1, 1.6, and 34 nM, respectively. At the cellular level, tofacitinib inhibits the in vitro activities of JAK1/JAK2, JAK1/JAK3, and JAK2/JAK2 combinations with IC50s of 406, 56, and 1377 nM, respectively.

Chemical Properties

Light Pink to Pale Orange Solid

Originator

Pfizer (United States)

Uses

CP-690550 is a pyrrolo[2,3-d]pyrimidine derivative, as Janus kinase inhibitor for treatment of rheumatoid arthritis

Definition

ChEBI: A pyrrolopyrimidine that is pyrrolo[2,3-d]pyrimidine substituted at position 4 by an N-methyl,N-(1-cyanoacetyl-4-methylpiperidin-3-yl)amino moiety. Used as its citrate salt to treat moderately to severely ctive rheumatoid arthritis.

Indications

The JAK family includes four isoforms, JAK1, JAK2, JAK3, and tyrosine kinase (TYK2). Ruxolitinib (Jakafi(R), Incyte Corp.) was the first approved JAK inhibitor, which inhibits both JAK1 and JAK2, used for the treatment of different types of myelofibrosis. Tofacitinib (Xeljanz(R), Pfizer) was approved by FDA as a JAK3-selective inhibitor for the treatment of rheumatoid arthritis and is one of the only two FDA-approved kinase inhibitors for non-oncological indications.

brand name

Xeljanz

Synthesis

Commercially available aminopyridine 171 was reacted with dimethyl dicarbonate in the presence of potassium t-butoxide to give the methyl carbamate 172 in 87% yield. Hydrogenation of this carbamate 172 in the presence of 20 wt% of 5% Rh/C (JM type C101023-5) in acetic acid followed by reductive amination with benzaldehyde and sodium triacetoxy borohydride furnished the cis-benzyl protected piperidine 173 in 73% yield. Reduction of the methyl carbamate within 173 with lithium aluminum hydride (LAH) in THF gave the corresponding methyl amino piperidine which was isolated as the dihydrochloride salt 174 in 87% yield. Enantiomeric resolution of the methyl amino piperidine was achieved by freebasing the di-hydrochloride salt 174 with sodium hydroxide and then conversion to the di-toluol-L-tartaric acid salt followed by crystallization to give 175 in 42% yield and 98.6% ee. The enantioenriched tartrate salt 175 was then directly reacted with dichloride 176 (obtained from reaction of commercial 7H-pyrrolo[2,3-d]pyrimidine-2,4-diol (178) with phosphorous oxychloride) in the presence of potassium carbonate in water to give the coupled product 177 in essentially quantitative yield. Hydrogenation of intermediate 177 with DeGussa?ˉs catalyst triggered concomitant debenzylation and chloride removal, and this was followed by installation of the cyanoacetate group and subsequent treatment with citric acid to provide tofacitinib citrate (XXVII) in 90% yield.

References

1) Jiang et al. (2008), Examining the chirality, confirmation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitril (CP-690,550); J. Mol. Chem., 51 8012 2) Cutolo and Meroni (2013), Clinical utility of the oral JAK inhibitor tofacitinib in the treatment of rheumatoid arthritis; J. Inflamm. Res., 6 129 3) Martina et al. (2016), Inhibition of JAK3 and PKC via Immunosuppressive Drugs Tofacitinib and Sotrastaurin Inhibits Proliferation of Human B Lymphocytes In Vitro; Transplant. Proc., 48 3046 4) Moisan et al. (2015), White-to-brown metabolic conversion of human adipocytes by JAK inhibition; Nat. Cell Biol., 17 57 5) Dowty et al. (2014), Preclinical to clinical translation of tofacitinib, a Janus kinase inhibitor, in rheumatoid arthritis; J. Pharmacol. Exp. Ther., 348 165

Tofacitinib Preparation Products And Raw materials

Raw materials

Preparation Products

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Tofacitinib Suppliers

Shanghai Boc Chemical Co.,Ltd
Tel
021-34975603-808 18721111801
Fax
+86-21-34975602-805
Email
sales@bocpharma.com
Country
China
ProdList
994
Advantage
64
Zhuhai Yourun Co., Ltd.
Tel
0756-6811852 13923369215
Fax
0756-6811857
Email
zhuhaiyourun@126.com
Country
China
ProdList
128
Advantage
55
Cangzhou Enke Pharma-tech Co., Ltd.
Tel
0317-5296180 15533709196
Fax
0317-5106596
Email
sale@enkepharma.com
Country
China
ProdList
1652
Advantage
55
Shanghai Mixiu Chemical Co., Ltd.
Tel
18101936766
Fax
021-58583907
Email
eileen@shmychem.com
Country
China
ProdList
351
Advantage
55
Junyu Chemexpress Co., Ltd.
Tel
0731-88036271 13723890100
Fax
0731-88036271
Email
info@csjyyy.com
Country
China
ProdList
47
Advantage
58
Hebei Chenguang Tianrun Pharma Co., Ltd.
Tel
0310-2816865 15175172220
Email
hbcgtr@126.com
Country
China
ProdList
9
Advantage
58
Shanghai Boyle Chemical Co., Ltd.
Tel
Fax
86-21-57758967
Email
sales@boylechem.com
Country
China
ProdList
2923
Advantage
55
J & K SCIENTIFIC LTD.
Tel
010-82848833 400-666-7788
Fax
86-10-82849933
Email
jkinfo@jkchemical.com
Country
China
ProdList
96815
Advantage
76
Chembest Research Laboratories Limited
Tel
021-20908456
Fax
021-58180499
Email
sales@BioChemBest.com
Country
China
ProdList
6013
Advantage
61
BeiJing Hwrk Chemicals Limted
Tel
0757-86329057 18501085097
Fax
010-89508210
Email
sales3.gd@hwrkchemical.com
Country
China
ProdList
7508
Advantage
55
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View Lastest Price from Tofacitinib manufacturers

Wuhan Boyuan Import & Export Co., LTD
Product
Tofacitinib 477600-75-2
Price
US $36.00-20.00/kg
Min. Order
1kg
Purity
99.50%
Supply Ability
20 tons
Release date
2023-07-04
Wuhan Boyuan Import & Export Co., LTD
Product
Tofacitinib 477600-75-2
Price
US $23.00-15.00/kg
Min. Order
1kg
Purity
99.50%
Supply Ability
20 tons
Release date
2023-07-05
Hebei Mojin Biotechnology Co., Ltd
Product
Tofacitinib 477600-75-2
Price
US $0.00/KG
Min. Order
1KG
Purity
99%
Supply Ability
50000KG/month
Release date
2023-06-30

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