(3S,4R)-Tofacitinib

Base Information

• Chemical Name: (3S,4R)-Tofacitinib
• CAS No.: 1092578-48-7
• Molecular Formula: C16H20N6O
• Molecular Weight: 312.37
• UNII: D2E2X7QH4A
• DSSTox Substance ID: DTXSID40433459
• Wikidata: Q72493072
• ChEMBL ID: CHEMBL459977
• Mol file: 1092578-48-7.mol

Synonyms:(3S,4R)-Tofacitinib;1092578-48-7;3-((3S,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile;D2E2X7QH4A;Epitofacitinib, (3S,4R)-;CHEMBL459977;3-[(3s,4r)-4-methyl-3-[methyl(7h-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-3-oxopropanenitrile;(3S,4R)-(-)-Tofacitinib isomer;CS-1107;UNII-D2E2X7QH4A;SCHEMBL23199919;DTXSID40433459;BDBM50273931;HY-40354B;NCGC00229511-01;AS-74810;F78359;J-501286;(3S,4R)-4-METHYL-3-(METHYL-7H-PYRROLO(2,3-D)PYRIMIDIN-4-YLAMINO)-.BETA.-OXO-1-PIPERIDINEPROPANENITRILE;(3S,4R)-4-Methyl-3-(methyl-7H-pyrrolo(2,3-d)pyrimidin-4-ylamino)-beta-oxo-1-piperidinepropanenitrile;1-PIPERIDINEPROPANENITRILE, 4-METHYL-3-(METHYL-7H-PYRROLO(2,3-D)PYRIMIDIN-4-YLAMINO)-.BETA.-OXO-, (3S,4R)-;1-Piperidinepropanenitrile, 4-methyl-3-(methyl-7H-pyrrolo(2,3-d)pyrimidin-4-ylamino)-beta-oxo-, (3S,4R)-;3-[(3S,4R)-4-methyl-3-[methyl({7H-pyrrolo[2,3-d]pyrimidin-4-yl})amino]piperidin-1-yl]-3-oxopropanenitrile

Chemical Property of (3S,4R)-Tofacitinib

Chemical Property:

• PKA: 6.04±0.60(Predicted)
• PSA: 88.91000
• Density: 1.296
• LogP: 1.48268
• XLogP3: 1.5
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 3
• Exact Mass: 312.16985928
• Heavy Atom Count: 23
• Complexity: 488

Purity/Quality:

98%,99%, ^*data from raw suppliers

(3S,4R)-Tofacitinib ^*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
• Isomeric SMILES: C[C@@H]1CCN(C[C@H]1N(C)C2=NC=NC3=C2C=CN3)C(=O)CC#N
• Uses: (3S,4R)-Tofacitinib is an enantiopure stereoisomer of the drug, Janus kinase 3(Jak3) inhibitor (CP-690,550) that has been found to inhibit selected members of the STE7 and STE20 subfamily of kinases.

Technology Process of (3S,4R)-Tofacitinib

There total 7 articles about (3S,4R)-Tofacitinib 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: 94.0%

N-methyl-N-((3S,4R)-4-methylpiperidine-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine + cyanoacetic acid (372-09-8) → tofacitinib (1092578-48-7,1259404-17-5)

Guidance literature:

cyanoacetic acid; With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; ethyl acetate; at 0 ℃; for 0.25h;

N-methyl-N-((3S,4R)-4-methylpiperidine-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine; With N-ethyl-N,N-diisopropylamine; In dichloromethane; ethyl acetate; at 0 - 20 ℃; for 12h;

Reference yield:

3-(tert-butoxycarbonylamino)pyridine (56700-70-0) → tofacitinib (1092578-48-7,1259404-17-5)

Guidance literature:

Multi-step reaction with 8 steps

1.1: tetrahydrofuran / 55 °C

2.1: sodium tetrahydroborate / 20 °C

3.1: C₈₂H₆₈Cl₂P₄Rh₂ / tetrahydrofuran / 12 h / 60 °C / Schlenk technique; Inert atmosphere

4.1: sodium hydride / tetrahydrofuran / 8 h / 25 °C

5.1: trifluoroacetic acid / dichloromethane / 6 h / 0 - 25 °C

6.1: potassium carbonate / N,N-dimethyl-formamide / 10 h / 90 °C

7.1: trifluoroacetic acid; palladium 10% on activated carbon; hydrogen / 50 °C

8.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane; ethyl acetate / 0.25 h / 0 °C

8.2: 12 h / 0 - 20 °C

With sodium tetrahydroborate; palladium 10% on activated carbon; C₈₂H₆₈Cl₂P₄Rh₂; hydrogen; sodium hydride; potassium carbonate; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; trifluoroacetic acid; In tetrahydrofuran; dichloromethane; ethyl acetate; N,N-dimethyl-formamide;

Reference yield:

N-benzyl-3-((tert-butoxycarbonyl)amino)pyridinium bromide (1415146-39-2) → tofacitinib (1092578-48-7,1259404-17-5)

Guidance literature:

Multi-step reaction with 7 steps

1.1: sodium tetrahydroborate / 20 °C

2.1: C₈₂H₆₈Cl₂P₄Rh₂ / tetrahydrofuran / 12 h / 60 °C / Schlenk technique; Inert atmosphere

3.1: sodium hydride / tetrahydrofuran / 8 h / 25 °C

4.1: trifluoroacetic acid / dichloromethane / 6 h / 0 - 25 °C

5.1: potassium carbonate / N,N-dimethyl-formamide / 10 h / 90 °C

6.1: trifluoroacetic acid; palladium 10% on activated carbon; hydrogen / 50 °C

7.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane; ethyl acetate / 0.25 h / 0 °C

7.2: 12 h / 0 - 20 °C

With sodium tetrahydroborate; palladium 10% on activated carbon; C₈₂H₆₈Cl₂P₄Rh₂; hydrogen; sodium hydride; potassium carbonate; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; trifluoroacetic acid; In tetrahydrofuran; dichloromethane; ethyl acetate; N,N-dimethyl-formamide;

upstream raw materials:

cyanoacetic acid

3-(tert-butoxycarbonylamino)pyridine

N-benzyl-3-((tert-butoxycarbonyl)amino)pyridinium bromide

C₁₄H₂₂N₂

Refernces

• 1、 Jiang, Jian-Kang,Ghoreschi, Kamran,Deflorian, Francesca,Chen, Zhi,Perreira, Melissa,Pesu, Marko,Smith, Jeremy,Nguyen, Dac-Trung,Liu, Eric H.,Leister, William,Costanzi, Stefano,O'Shea, John J.,Thomas, Craig J.. "Examining the chirality, conformation 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-oxopropanenitrile (CP-690,550)". supporting information; experimental part. p. 8012 - 8018. Retrieved 2009/12/07.