Raltitrexed

Base Information

• Chemical Name: Raltitrexed
• CAS No.: 112887-68-0
• Molecular Formula: C21H22N4O6S
• Molecular Weight: 458.495
• Mol file: 112887-68-0.mol

Synonyms:D1694;Tomudex (TN);L-Glutamic acid,N-[[5-[[(1,4-dihydro-2- methyl-4-oxo-6-quinazolinyl)methyl]methylamino]- 2-thienyl]carbonyl]-;ZD1694;Raltitrexed (JAN/USAN);D 1694;(2S)-2-[[5-[methyl-[(2-methyl-4-oxo-1H-quinazolin-6-yl)methyl]amino]thiophene-2-carbonyl]amino]pentanedioic acid;L-Glutamic acid, N-((5-(((1,4-dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl)methylamino)-2-thienyl)carbonyl)-;Tomudex;ICI-D1694;ICI D1694;N-(5-(N-(3,4-Dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino)-2-thenoyl)-L-glutamic acid;(S)-2-[(1-{5-[Methyl-(2-methyl-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl)-amino]-thiophen-2-yl}-methanoyl)-amino]-pentanedioic acid;ZD 1694;D-1694;

Chemical Property of Raltitrexed

Chemical Property:

• Appearance/Colour: yellow crystalline powder
• Melting Point: 176-180 °C
• Refractive Index: 1.638
• PKA: 3.50±0.10(Predicted)
• PSA: 180.93000
• Density: 1.49 g/cm³
• LogP: 2.36810
• Storage Temp.: Hygroscopic, -20°C Freezer, Under Inert Atmosphere
• Solubility.: H2O: ≥10mg/mL

Purity/Quality:

99% ^*data from raw suppliers

Raltitrexed ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi,T
• Statements: 36/38-25-61
• Safety Statements: 26-37/39-45-53

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Description: Tomudex was launched in Ireland, France, Luxembourg and the UK for advanced colorectal cancer and it was prepared in a convergent manner (6 steps) from diethyl L-glutamate and 6-bromomethyi-2-methyl-quinazolin4(3H)-one. Tomudex is a highly selective inhibitor of thymidylate synthase (TS), the key enzyme in the biochemical conversion of dUMP to dTMP. It enters the cell via the reduced folatefmethotrexate cell membrane carrier and is converted to the polyglutamate species by folylpolyglutamate synthase within 4h where it then binds to the folate substrate site of TS. Clinically, it had a 29% response rate in patients with advanced colorectal cancer. It is water soluble, can be administered as a single dose every three weeks and had no hepto- or nephrotoxicity.
• Uses: Folate-based inhibitor of thymidylate synthase; rapidly and extensively metabolized to its more potent polyglutamate derivatives. Antineoplastic
• Clinical Use: Treatment of colorectal cancer when fluorouracil and folinic acid cannot be used
• Drug interactions: Potentially hazardous interactions with other drugs Antipsychotics: avoid with clozapine, increased risk of agranulocytosis. Folic and folinic acid: impairs cytotoxic action - avoid.

Technology Process of Raltitrexed

There total 29 articles about Raltitrexed 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: 88.6%

N-[[5-[N-(3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl]-N-methyl]amino-2-thiophenecarbonyl]-L-glutamic acid diethyl ester (132463-02-6) → N-[5-[N-[(3,4-dihydro-2-methyl-4-oxy-6-quinazolinyl)-methyl]-N-methylamino]-2-thenoyl]-L-glutamic acid (112887-68-0)

Guidance literature:

With sodium hydroxide; In ethanol; at 20 ℃; for 2h;

DOI:10.1081/SCC-120024732

Reference yield:

N-(5-aminothiophene-2-carbonyl)-L-glutamic acid diethyl ester (106585-63-1) → N-[5-[N-[(3,4-dihydro-2-methyl-4-oxy-6-quinazolinyl)-methyl]-N-methylamino]-2-thenoyl]-L-glutamic acid (112887-68-0)

Guidance literature:

Multi-step reaction with 3 steps

1: 48 percent / 2,6-lutidine / dimethylformamide; toluene / 24 h / 70 °C

2: 22 percent / 2,6-lutidine / various solvent(s) / 18 h / 80 °C

3: 41 percent / 1 N aq. NaOH / 2 h

With 2,6-dimethylpyridine; sodium hydroxide; In N,N-dimethyl-formamide; toluene;

DOI:10.1021/jm00109a011

Reference yield:

N-(5-methylamino-2-thiophenecarbonyl)-L-glutamic acid diethyl ester (112889-02-8) → N-[5-[N-[(3,4-dihydro-2-methyl-4-oxy-6-quinazolinyl)-methyl]-N-methylamino]-2-thenoyl]-L-glutamic acid (112887-68-0)

Guidance literature:

Multi-step reaction with 2 steps

1: 74.2 percent / 2,6-lutidine / dimethylformamide / 55 - 60 °C

2: 88.6 percent / 1 N aq. NaOH / ethanol / 2 h / 20 °C

With 2,6-dimethylpyridine; sodium hydroxide; In ethanol; N,N-dimethyl-formamide;

DOI:10.1081/SCC-120024732

upstream raw materials:

N-[[5-[N-(3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl]-N-methyl]amino-2-thiophenecarbonyl]-L-glutamic acid diethyl ester

Thiophene-2,5-dicarboxylic acid

L-glutamic acid diethyl ester

4(3H)-oxo-6-(bromomethyl)-2-methyl quinazoline