73978-41-3

Usage

Uses

Used in Pharmaceutical Industry:
(2,4-Diamino-pteridin-6-yl)methanol hydrochloride hydrate is used as a methotrexate intermediate for the synthesis of methotrexate, a widely used anti-cancer and anti-inflammatory drug. It plays a crucial role in the production of this medication, contributing to its effectiveness in treating various conditions.
Used in Chemical Synthesis:
(2,4-Diamino-6-(hydroxymethyl)pteridine hydrochloride) may be used in the synthesis of 6-bromomethyl-pteridine-2,4-diamine, a compound with potential applications in various chemical and pharmaceutical processes. This versatile intermediate allows for the creation of new compounds with diverse uses.

InChI:InChI=1/C7H8N6O.ClH.H2O/c8-5-4-6(13-7(9)12-5)10-1-3(2-14)11-4;;/h1,14H,2H2,(H4,8,9,10,12,13);1H;1H2

Synthetic route

2,4,5,6-tetraaminopyrimidine (1004-74-6) + dihydroxyacetone (96-26-4) → 2,4-diamino-6-(hydroxymethyl)pteridine hydrochloride (73978-41-3)

Conditions	Yield
With oxygen; DL-cysteine hydrochloride; ammonium chloride In water for 36h;	70%

dihydroxyacetone (96-26-4) + 2,4,5,6-tetraaminopyrimidine sulfate (5392-28-9) → 2,4-diamino-6-(hydroxymethyl)pteridine hydrochloride (73978-41-3)

Conditions	Yield
With ammonium hydroxide; l-cysteine hydrochloride; oxygen; ammonium chloride; barium(II) chloride 1.) H2O, 90 deg C, 15 min, 2.) H2O, RT, 45 h; Yield given. Multistep reaction;

1,3-dihydroxyacetone dimer (62147-49-3) + barium chloride dihydrate + 2,4,5,6-tetraminopyrimidine sulfate monohydrate + DL-cysteine hydrochloride (10318-18-0) → 2,4-diamino-6-(hydroxymethyl)pteridine hydrochloride (73978-41-3)

Conditions	Yield
With ammonium chloride In water	17.2 g (45%)

Upstream product

• 1004-74-6 2,4,5,6-tetraaminopyrimidine 
• 96-26-4 dihydroxyacetone 
• 5392-28-9 2,4,5,6-tetraaminopyrimidine sulfate 
• 62147-49-3 1,3-dihydroxyacetone dimer 
• 10318-18-0 DL-cysteine hydrochloride 

Downstream Products

• 712-29-8 6-(hydroxymethyl)pterin 
• 945-24-4 2,4-diamino-6-(hydroxymethyl)pteridine 
• 59368-16-0 6-bromomethyl-pteridine-2,4-diamine 
• 52853-40-4 6-bromomethyl-2,4-diaminopteridine hydrobromide 
• 19741-14-1 4-[(2,4-diaminopteridin-6-ylmethyl)methylamino]benzoic acid 
• 79640-70-3 (S)-5-(tert-butoxy)-4-(4-(((2,4-diaminopteridin-6-yl)methyl)(methyl)amino)benzamido)-5-oxopentanoic acid 

Relevant academic research and scientific papers

Pteridine derivatives and method of treating leukemia employing same

2,4-Diaminopteridine derivatives and the pharmaceutically acceptable salts thereof having potent anticancer activity are disclosed. The derivatives possess the structural formula: STR1 wherein Y is NH2, OH or SH, R is STR2 and X is STR3 in which R' is H or CH3 or STR4 in which R and R' are as previously defined, provided when Y is NH2, R' must be CH3 and when Y is OH, R' must be OH.

Methotrexate analogues. 25. Chemical and biological studies on the γ-tert-Butyl esters of methotrexate and aminopterin

γ-tert-Butylaminopterin (γ-tBAMT), the first example of an aminopterin (AMT) γ-monoester, was synthesized, and new routes to the known N10-methyl analogue γ-tert-butyl methotrexate (γ-tBMTX were developed. The inhibitory effects of γ-tBAMT on the activity of purified dihydrofolate reductase (DHFR) from L1210 murine leukemia cells, the growth of L1210 cells and CEM human leukemic lymphoblasts in suspension culture, and the growth of several lines of human squamous cell carcinoma of the head and neck in monolayer culture were compared with the effects of γ-tBMTX and the parent acids AMT and methotrexate (MTX). Patterns of cross-resistance to γ-tBAMT, γ-tBMTX, and AMT among several MTX-resistant cell lines were examined. In vivo antitumor activities of γ-tBAMT and γ-tBMTX were compared in mice with L1210 leukemia. While the activity of γ-tBAMT was very close to that of γ-tBMTX in the DHFR inhibition assay, the AMT ester was more potent than the MTX ester against cells in culture and against L1210 leukemia in vivo. Only partial cross-resistance was shown against γ-tBMTX and γ-tBAMT in cultured cells that were resistant to MTX by virtue of a transport defect or a combination of defective transport and elevated DHFR activity.

Pteridines, LXIX. Synthesis and Reactivity of 2,4-Diamino-6-(hydroxymethyl)pteridine

Condensation of 2,4,5,6-tetraaminopyridine (2) with 1,3-dihydroxyacetone in the presence of gaseous oxygen, rather than air, resulted in 2,4-diamino-6-(hydroxymethyl)pteridine (3) virtually uncontaminated with 2,4-diamino-6-methylpteridine (4).Acetylation of 3 led to 6-acetoxymethyl-2,4-bis(acetylamino)pteridine (5) which turned out to be very labile forming various di- and monoacetyl derivatives (6, 7, 9, 10) on mild hydrolytic conditions.Their structures are proven by physical-chemical means.Silylation of 3 to the tris(trimethylsilyl) derivative 11 followed by treatment with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose (12) and 1,2,3,4,6-penta-O-acetyl-β-D-glucopyranose (15), respectively, in the presence of boron trifluoride,led to selective formation of the corresponding acylated 2,4-diamino-6-pteridinyl O-glycosides 13 and 15, respectively.Deacylations of these afforded the free O-glycosides 14 and 17 which have been characterized by UV- and NMR spectra as well as pKa measurements.