Methotrexate 5-methyl ester

Base Information

• Chemical Name: Methotrexate 5-methyl ester
• CAS No.: 67022-39-3
• Molecular Formula: C21H24N8O5
• Molecular Weight: 468.46586
• European Community (EC) Number: 807-811-6
• UNII: 98597RH43H
• ChEMBL ID: CHEMBL3245811
• Nikkaji Number: J558.276H
• Wikidata: Q27272084
• Mol file: 67022-39-3.mol

Synonyms:Methotrexate 5-methyl ester;67022-39-3;Methotrexate |A-Methyl Ester;98597RH43H;(2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]-5-methoxy-5-oxopentanoic acid;(S)-2-(4-(((2,4-diaminopteridin-6-yl)methyl)(methyl)amino)benzamido)-5-methoxy-5-oxopentanoic acid;Methotrexate gamma-methyl ester;(2S)-2-((4-(((2,4-Diaminopteridin-6-yl)methyl)methylamino)benzoyl)amino)-5-methoxy-5-oxopentanoic acid;L-Glutamic acid, N-(4-(((2,4-diamino-6-pteridinyl)methyl)methylamino)benzoyl)-, 5-methyl ester;CHEMBL3245811;SCHEMBL15469224;UNII-98597RH43H;AKOS040747152;Methotrexate specified impurity H [EP];(2S)-2-[[4-[[(2,4-Diaminopteridin-6-yl)methyl]methylamino]benzoyl]amino]-5-methoxy-5-oxopentanoic Acid (Methotrexate 5-Methyl Ester);HY-135101;CS-0109351;METHOTREXATE IMPURITY H [EP IMPURITY];A899872;Q27272084;L-Glutamic acid, N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-, 5-methyl ester;Methotrexate 5-Methyl Ester;Methotrexate Imp. H (EP);Methotrexate Related Compound H;Methotrexate Impurity H

Chemical Property of Methotrexate 5-methyl ester

Chemical Property:

• Melting Point: 170-174 °C
• PKA: 3.43±0.10(Predicted)
• PSA: 200.27000
• Density: 1.459±0.06 g/cm3(Predicted)
• LogP: 1.25900
• XLogP3: -1.5
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 12
• Rotatable Bond Count: 10
• Exact Mass: 468.18696590
• Heavy Atom Count: 34
• Complexity: 719

Purity/Quality:

99% ^*data from raw suppliers

Methotrexateγ-MethylEster ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CN(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)NC(CCC(=O)OC)C(=O)O
• Isomeric SMILES: CN(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)N[C@@H](CCC(=O)OC)C(=O)O
• Uses: Methotrexate γ-methyl ester is an impurity of Methotrexate (M260675), a folic acid antagonist. Used as a antineoplastic and antirheumatic.

Technology Process of Methotrexate 5-methyl ester

There total 13 articles about Methotrexate 5-methyl ester 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: 88.0%

α-tert-butyl γ-methyl N'-<4--N-methylamino>benzoyl>-L-glutamate (79648-88-7) → γ-methyl N'-<4--N-methylamino>benzoyl>-L-glutamate (67022-39-3)

Guidance literature:

With boron trifluoride diethyl etherate; In 1,2-dichloro-ethane; for 18h;

DOI:10.1021/jm00131a003

Reference yield: 73.0%

methanol (67-56-1) + N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid (59-05-2) → dimethyl N-(4-(((2,4-diaminopteridin-6-yl)methyl)(methyl)amino)benzoyl)-L-glutamate (34378-65-9) + γ-methyl N'-<4--N-methylamino>benzoyl>-L-glutamate (67022-39-3)

Guidance literature:

With sodium sulfate; tetrafluoroboric acid diethyl ether; for 18h; Ambient temperature;

DOI:10.1021/jm00131a003

Reference yield: 57.0%

dimethyl N-(4-(((2,4-diaminopteridin-6-yl)methyl)(methyl)amino)benzoyl)-L-glutamate (34378-65-9) → γ-methyl N'-<4--N-methylamino>benzoyl>-L-glutamate (67022-39-3)

Guidance literature:

With N,N-Dimethylhydrazine; for 48h; Heating;

DOI:10.1021/jm00137a016

upstream raw materials:

dimethyl N-(4-(((2,4-diaminopteridin-6-yl)methyl)(methyl)amino)benzoyl)-L-glutamate

L-glutamic acid 5-methyl ester

4-[(2,4-diaminopteridin-6-ylmethyl)methylamino]benzoic acid

6-bromomethyl-2,4-diaminopteridine hydrobromide

Downstream raw materials:

(S)-2-{4-[(2,4-Diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoylamino}-4-[2,2,2-trifluoro-eth-(E)-ylidene-hydrazinocarbonyl]-butyric acid

(S)-4-Azidocarbonyl-2-{4-[(2,4-diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoylamino}-butyric acid

methotrexate α,γ-bis(methyl 2-aminotetradecanoate)

N'-<4--N-methylamino>benzoyl>-L-glutamic acid γ-hydrazide

Refernces

• 1、 Kralovec,Spencer,Blair,Mammen,Singh,Ghose. "Synthesis of methotrexate-antibody conjugates by regiospecific coupling and assessment of drug and antitumor activities". . p. 2426 - 2431. Retrieved 2007/10/02.
• 2、 Rosowsky, Andre,Yu, Cheng-Sein,Uren, Jack,Lazarus, Herbert,Wick, Michael. "Methotrexate Analogues. 13. Chemical and Pharmacological Studies on Amide, Hydrazide, and Hydroxamic Acid Derivatives of the Glutamate Side Chain". . p. 559 - 567. Retrieved 2007/10/02.