7413-34-5

Basic information

• Product Name: Methotrexate disodium salt
• Synonyms: 4-amino-n(sup10)-methylpteroylglutamicaciddisodiumsalt;amethopterinsodium;disodiummethotrexate;l-(+)-isodiumsal;mtxdisodium;METHOTREXATE DISODIUM;METHOTREXATE DISODIUM SALT;Disodium N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamate
• CAS NO: 7413-34-5
• Molecular Formula: C₂₀H₂₀N₈O₅*2Na
• Molecular Weight: 498.4
• EINECS: 231-022-0
• Product Categories: API;Molecular biology Products;Anti-cancer&immunity
• Mol File: 7413-34-5.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 823℃
• Appearance: /
• Storage Temp.: 0-6°C
• Water Solubility: Soluble in water
• Sensitive: Hygroscopic
• CAS DataBase Reference: Methotrexate disodium salt(CAS DataBase Reference)
• NIST Chemistry Reference: Methotrexate disodium salt(7413-34-5)
• EPA Substance Registry System: Methotrexate disodium salt(7413-34-5)

Safety Data

• RTECS: MA1232000
• HazardClass: 6.1
• Hazardous Substances Data: 7413-34-5(Hazardous Substances Data)

Usage

Uses

Inhibits the metabolism of folic acid

InChI:InChI=1/C20H22N8O5.2Na/c1-28(9-11-8-23-17-15(24-11)16(21)26-20(22)27-17)12-4-2-10(3-5-12)18(31)25-13(19(32)33)6-7-14(29)30;;/h2-5,8,13H,6-7,9H2,1H3,(H,25,31)(H,29,30)(H,32,33)(H4,21,22,23,26,27);;/q;2*+1/p-2

Synthetic route

dicyanomethyl N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamate (1379609-57-0) → disodium methotrexate (7413-34-5)

Conditions	Yield
Stage #1: dicyanomethyl N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamate With water; potassium hydroxide In methanol at 20℃; for 0.333333h; Stage #2: With hydrogenchloride In methanol; water pH=4.2; Stage #3: With sodium hydroxide In water for 0.0833333h; pH=10;	89%

N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid (59-05-2) → disodium methotrexate (7413-34-5)

Conditions	Yield
With sodium hydroxide In water
With sodium hydroxide In methanol at 40℃; for 2h;

N-[4-(methylamino)benzoyl]-L-glutamic acid disodium → disodium methotrexate (7413-34-5)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium carbonate / N,N-dimethyl-formamide / 60 °C 2.1: water / 1 h / 58 - 62 °C / pH 2.4 3.1: potassium hydroxide; water / methanol / 0.33 h / 20 °C 3.2: pH 4.2 3.3: 0.08 h / pH 10 View Scheme

1-dodecylbromide (143-15-7) + disodium methotrexate (7413-34-5) → (S)-2-{4-[(2,4-Diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoylamino}-pentanedioic acid didodecyl ester (86669-30-9)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 20℃; for 24h;	98%

disodium methotrexate (7413-34-5) + 2,6-Dichlorobenzyl bromide (20443-98-5) → bis(2,6-dichlorobenzyl) methotrexate (86669-36-5)

Conditions	Yield
In dimethyl sulfoxide for 3h; Ambient temperature;	64%

2-chloromethyl-1,3,5-trimethylbenzene (1585-16-6) + disodium methotrexate (7413-34-5) → bis(2,4,6-trimethylbenzyl) methotrexate (86669-35-4)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide for 24h; Ambient temperature;	49%

1-bromo-butane (109-65-9) + disodium methotrexate (7413-34-5) → di-n-butyl methotrexate (50602-77-2)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide

1-bromo-hexane (111-25-1) + disodium methotrexate (7413-34-5) → C32H46N8O5 (50602-79-4)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide

1-bromo-octane (111-83-1) + disodium methotrexate (7413-34-5) → di-n-octyl methotrexate (50602-80-7)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide

Upstream product

• 60388-53-6 methotrexate 
• 59-05-2 N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid 
• 1379609-57-0 dicyanomethyl N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamate 

Downstream Products

• 50602-80-7 di-n-octyl methotrexate 
• 50602-79-4 C₃₂H₄₆N₈O₅ 
• 50602-77-2 di-n-butyl methotrexate 
• 86669-35-4 bis(2,4,6-trimethylbenzyl) methotrexate 
• 86669-30-9 (S)-2-{4-[(2,4-Diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoylamino}-pentanedioic acid didodecyl ester 
• 86669-36-5 bis(2,6-dichlorobenzyl) methotrexate 
• 5472-96-8 3'-monochloromethotrexate 
• 528-74-5 3',5'-dichloro-methotrexate 

Relevant articles and documents

Anticancer drug encapsulated in inorganic lattice can overcome drug resistance

A methotrexate (MTX)-layered double hydroxide (LDH) hybrid have been developed as a drug delivery system, in which an anticancer drug, MTX, was intercalated into a 2-dimensional LDH nanovehicle to form a nanohybrid. According to the comparative cell viability studies between MTX only and its LDH nanohybrid on MTX sensitive and resistant cell culture lines, it was found that the MTX-LDH nanohybrid could bypass the MTX resistance and eventually inhibit cancer cell proliferation very effectively compared to free MTX, due to an enhanced permeability and retention effect of MTX-LDH nanoparticles even in dihydrofolate reductase-overexpressing MTX-resistant cells. This is definitely associated with the uptake mechanism via a clathrin-mediated endocytic pathway for the MTX-LDH nanohybrid particles, the same as for the LDH nanocarrier only, which is completely different from the cellular uptake mechanism for MTX only, the reduced folate carrier (RFC) and/or the folate receptor entries.

A NEW METHOD FOR PRODUCING ANTIFOLATE AGENTS HAVING GLUTAMIC ACID PART IN THEIR STRUCTURE

A new method for producing antifolate agents having glutamic acid part in their structure is developed by protecting carboxyl groups of glutamic acid or its N-subsituted derivatives as cyanomethyl ester to give compounds of formula (II) which are hydrolyzed under very mild conditions to afford antifolate agents in high yield with high analytical and optical purity.