52853-40-4

Basic information

• Product Name: 6-BROMOMETHYL-PTERIDINE-2,4-DIAMINE HBR
• Synonyms: 2,4-pteridinediaMine, 6-(broMoMethyl)-, hydrobroMide;2, 4-diaMino-6-(broMoMethyl)-pteridine HCL;2,4-diamino-6-(bromomethyl)pteridine(for methotrexate);6-BROMOMETHYL-PTERIDINE-2,4-DIAMINE HBR;2,4-Diamino-6-(bromomethyl)pteridine Hydrobromide;6-(Bromomethyl)-2,4-diaminopteridine Hydrobromide;Nsc253943;6-Bromomethyl-pteridine-2,4-diamine hydrobromide
• CAS NO: 52853-40-4
• Molecular Formula: BrH*C₇H₇BrN₆
• Molecular Weight: 335.98662
• EINECS: 1308068-626-2
• Product Categories: Aromatics Compounds;Aromatics;Bases & Related Reagents;Inhibitors;Nucleotides
• Mol File: 52853-40-4.mol
• Article Data: 7

Chemical Properties

• Melting Point: >195°C (dec.)
• Boiling Point: 524.7 °C at 760 mmHg
• Flash Point: 271.1 °C
• Appearance: light brown solid
• Vapor Pressure: 1.6E-11mmHg at 25°C
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Slightly)
• CAS DataBase Reference: 6-BROMOMETHYL-PTERIDINE-2,4-DIAMINE HBR(CAS DataBase Reference)
• NIST Chemistry Reference: 6-BROMOMETHYL-PTERIDINE-2,4-DIAMINE HBR(52853-40-4)
• EPA Substance Registry System: 6-BROMOMETHYL-PTERIDINE-2,4-DIAMINE HBR(52853-40-4)

Safety Data

• Hazardous Substances Data: 52853-40-4(Hazardous Substances Data)

Usage

Chemical Properties

Light Brown Solid

Uses

6-(Bromomethyl)-2,4-pteridinediamine hydrobromide can be used as organic synthesis intermediate and pharmaceutical intermediate.

Application

6-(Bromomethyl)-2,4-pteridinediamine Hydrobromide (Technical Grade) is a useful research chemical used in the preparation of novel methotrexate derivatives as antirheumatic agents as well as the preparation of pteridine reductase inhibitors.

InChI:InChI=1/C7H7BrN6.BrH/c8-1-3-2-11-6-4(12-3)5(9)13-7(10)14-6;/h2H,1H2,(H4,9,10,11,13,14);1H

Synthetic route

β-bromopyruvaldoxime + 2,4,5,6-tetraminopyrimidine dihydrobromide → 6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4)

Conditions	Yield
Stage #1: β-bromopyruvaldoxime; 2,4,5,6-tetraminopyrimidine dihydrobromide In methanol for 2h; Heating / reflux; Stage #2: With ammonia at 20℃; for 2h; Product distribution / selectivity;	88%

3-bromoacetonaldoxime (37150-52-0) + 2,4,5,6-tetraminopyrimidine dihydrobromide → 6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4)

Conditions	Yield
In methanol for 2h; Heating / reflux;	88%

2,4-diamino-6-hydroxymethylpteridine hydrobromide → 6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4)

Conditions	Yield
With dibromotriphenylphosphorane In dimethylacetamide (DMAC) at 20 - 25℃; for 2h; Product distribution / selectivity;	49%
With dibromotriphenylphosphorane In ISOPROPYLAMIDE at 10 - 25℃; for 2h;	42%

2,4-diamino-6-(hydroxymethyl)pteridine (945-24-4) → 6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4)

Conditions	Yield
With bromine; triphenylphosphine In N,N-dimethyl acetamide at 25℃; for 18h;
With hydrogen bromide; acetic acid at 20℃; for 48h;
With triphenylphosphine dibromide; N,N-dimethyl acetamide at 20℃; for 200h;

2,4-diamino-6-hydroxymethylpteridine hydrobromide + 2,4-diamino-6-(hydroxymethyl)pteridine hydrochloride (73978-41-3) → 6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4)

Conditions	Yield
With ammonium hydroxide; hydrogen bromide; bromine; triphenylphosphine In ethanol; N,N-dimethyl acetamide; water; acetic acid; benzene

2,4-diamino-6-pteridinemethanol.HRr + diethyl ether (60-29-7) → 6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4)

Conditions	Yield
With sodium hydroxide; bromine; triphenylphosphine In methanol; glacial AcOH; P2 O5; ethanol

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + N2-<4-(methylamino)benzoyl>-Nω-<(1,1-dimethylethoxy)carbonyl>-2,ω-diaminopentanoic acid (96845-99-7) → N2-<4-<<(2,4-diamino-6-pteridinyl)methyl>methylamino>benzoyl>-N5-<(1,1-dimethylethoxy)carbonyl>-2,5-diaminopentanoic acid (96846-16-1)

Conditions	Yield
In N,N-dimethyl acetamide at 20 - 25℃; for 120h;	95%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + N-{4-[(2,3-Dihydro-1H-indole-5-carbonyl)-amino]-4-methoxycarbonyl-butyl}-terephthalamic acid methyl ester → N-(4-{[1-(2,4-Diamino-pteridin-6-ylmethyl)-2,3-dihydro-1H-indole-5-carbonyl]-amino}-4-methoxycarbonyl-butyl)-terephthalamic acid methyl ester

Conditions	Yield
In N,N-dimethyl acetamide at 65℃; for 5h;	93%

dicyanomethyl N-[4-(methylamino)benzoyl]-L-glutamic acid (1379609-56-9) + 6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) → dicyanomethyl N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamate (1379609-57-0)

Conditions	Yield
In water at 58 - 62℃; for 1h; pH=2.4;	87%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + α-tert-butyl-N-[4-(methylamino)benzoyl]-L-glutamate (511544-87-9) → (S)-5-(tert-butoxy)-4-(4-(((2,4-diaminopteridin-6-yl)methyl)(methyl)amino)benzamido)-5-oxopentanoic acid (79640-70-3)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 31h;	86%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + Nα-<4-(N-methylamino)benzoyl>-Nδ-<1-ethoxycarbonyl-3,3-bis(diethylphosphono)propyl>glutamine benzyl ester → Nα-<4-amino-4-deoxy-N-10-methylpteroyl>-Nδ-<1-ethoxycarbonyl-3,3-bis(diethylphosphono)propyl>glutamine benzyl ester

Conditions	Yield
In N,N-dimethyl acetamide at 50℃; for 4h;	80%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + 2-Fluoro-4-(4-methylamino-benzoylamino)-pentanedioic acid diisopropyl ester (95755-25-2) → 2-{4-[(2,4-Diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoylamino}-4-fluoro-pentanedioic acid diisopropyl ester (95772-55-7)

Conditions	Yield
In N,N-dimethyl acetamide at 55℃; for 10h;	79.1%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + N2-<4-(methylamino)benzoyl>-Nω-<(1,1-dimethylethoxy)carbonyl>-2,ω-diaminopropanoic acid ethyl ester (96845-97-5) → (S)-3-tert-Butoxycarbonylamino-2-{4-[(2,4-diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoylamino}-propionic acid ethyl ester (96846-12-7)

Conditions	Yield
In N,N-dimethyl acetamide for 144h;	79%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + (S)-4-tert-Butoxycarbonylamino-2-(4-methylamino-benzoylamino)-butyric acid ethyl ester (96845-98-6) → (S)-4-tert-Butoxycarbonylamino-2-{4-[(2,4-diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoylamino}-butyric acid ethyl ester (96846-13-8)

Conditions	Yield
In N,N-dimethyl acetamide for 144h;	79%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + (S)-2-((S)-4-Carboxy-4-{(S)-4-carboxy-4-[(S)-4-carboxy-4-(4-methylamino-benzoylamino)-butyrylamino]-butyrylamino}-butyrylamino)-pentanedioic acid (83816-96-0) → N-methylamino>benzoyl>-L-γ-glutamyl>-L-γ-glutamyl>-L-γ-glutamyl>-L-γ-glutamic acid (73610-81-8)

Conditions	Yield
In N,N-dimethyl acetamide at 25℃; for 144h;	78%

dibenzoazepine (256-96-2) + 6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) → N-[(2,4-diaminopteridin-6-yl)methyl]dibenz[b,f]azepine

Conditions	Yield
Stage #1: dibenzoazepine With sodium hydride In tetrahydrofuran for 0.166667h; Metallation; Stage #2: 6-bromomethyl-2,4-diaminopteridine hydrobromide In tetrahydrofuran at 20℃; for 12h; Alkylation;	78%
Stage #1: dibenzoazepine With sodium hydride In tetrahydrofuran at 0℃; for 0.166667h; Stage #2: 6-bromomethyl-2,4-diaminopteridine hydrobromide In tetrahydrofuran at 20℃; Product distribution / selectivity;	17%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + α-methyl γ-tert-butyl N--L-glutamate (95485-08-8) → α-methyl γ-tert-butyl N-(4-amino-4-deoxy-N10-methylpteroyl)-L-glutamate (79640-68-9)

Conditions	Yield
In N,N-dimethyl acetamide at 55℃; for 6h;	75%
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl acetamide at 45℃; for 48h; Yield given;

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + 2-[(2,3-Dihydro-1H-indole-5-carbonyl)-amino]-5-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-pentanoic acid methyl ester → 2-{[1-(2,4-Diamino-pteridin-6-ylmethyl)-2,3-dihydro-1H-indole-5-carbonyl]-amino}-5-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-pentanoic acid methyl ester

Conditions	Yield
In N,N-dimethyl acetamide at 65℃; for 5h;	75%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + α-propargylhomoterephthalic acid dimethyl ester (146464-90-6) → 10-propargyl-10-carbomethoxy-4-deoxy-4-amino-10-deazapteroic acid methyl ester hydrobromide salt (1548618-47-8)

Conditions	Yield
Stage #1: 6-bromomethyl-2,4-diaminopteridine hydrobromide; α-propargylhomoterephthalic acid dimethyl ester With sodium hydride In N,N-dimethyl acetamide at -20 - -10℃; Stage #2: With hydrogen bromide In methanol; dichloromethane; water; isopropyl alcohol at 0 - 5℃; Concentration;	73.7%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) → 2-amino-6-(bromomethyl)-4(1H)-pteridinone hydrobromide (59212-10-1)

Conditions	Yield
With hydrogen bromide at 90 - 95℃; for 0.5h;	72%

tyrosine tert-butyl ester (88878-78-8) + 6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) → 2-[(2,4-Diamino-pteridin-6-ylmethyl)-amino]-3-(4-hydroxy-phenyl)-propionic acid tert-butyl ester

Conditions	Yield
In N,N-dimethyl acetamide	71%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + Nα-<4-(methylamino)benzoyl>-Nδ-<2,2-bis(diethylphosphono)ethyl>glutamine ethyl ester (147938-30-5) → Nα-<4-<(<2,4-diamino-6-pteridinyl>methyl)methylamino>benzoyl>-Nδ-<2,2-bis(diethylphosphono)ethyl>glutamine ethyl ester (147938-31-6)

Conditions	Yield
In N,N-dimethyl acetamide at 50℃; for 4h;	70%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + phenol (108-95-2) → 6-phenoxymethyl-pteridine-2,4-diamine (57963-57-2)

Conditions	Yield
With NaH	70%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + tetraethyl 3-ethoxycarbonyl-N-<4-(methylamino)benzoyl>-3-aminopropylidene-1,1-bisphosphonate (120355-34-2) → tetraethyl N-(4-<(<2,4-diamino-6-pteridinyl>methyl) methyl-amino>benzoyl)-3-amino-3-ethoxycarbonylpropylidene-1,1-bisphosphonate (120368-87-8)

Conditions	Yield
In N,N-dimethyl acetamide at 50℃; for 4h;	68%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + (S)-2-(4-Methylamino-benzoylamino)-3-ureido-propionic acid (96846-06-9) → (S)-2-{4-[(2,4-Diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoylamino}-3-ureido-propionic acid (96846-09-2)

Conditions	Yield
In N,N-dimethyl acetamide at 20 - 25℃; for 120h;	68%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + (S)-2-[(3,4-Dihydro-2H-benzo[1,4]oxazine-7-carbonyl)-amino]-hexanedioic acid dimethyl ester (142166-04-9) → (S)-2-{[4-(2,4-Diamino-pteridin-6-ylmethyl)-3,4-dihydro-2H-benzo[1,4]oxazine-7-carbonyl]-amino}-hexanedioic acid dimethyl ester (142166-37-8)

Conditions	Yield
In N,N-dimethyl acetamide at 60℃; for 4h;	68%

N-(4-aminobenzoyl)-L-glutamic acid (4271-30-1) + water (7732-18-5) + 6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) → aminopterin (54-62-6)

Conditions	Yield
In ethanol	68%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + (S)-2-{(S)-4-Carboxy-4-[(S)-4-carboxy-4-(4-methylamino-benzoylamino)-butyrylamino]-butyrylamino}-pentanedioic acid (83816-95-9) → N-methylamino>benzoyl>-L-γ-glutamyl>-L-γ-glutamyl>-L-γ-glutamic acid (41600-14-0)

Conditions	Yield
In N,N-dimethyl acetamide at 25℃; for 144h;	67%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + diethyl N-<4-(octylamino)benzoyl>-L-glutamate (82318-20-5) → diethyl N-<4-<<(2,4-diamino-6-pteridinyl)methyl>octylamino>benzoyl>-L-glutamate (82318-22-7)

Conditions	Yield
In N,N-dimethyl acetamide 1.) from 50 to 55 deg C, 6 h, 2.) 25 deg C, 18 h;	67%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + (S)-2-[(7-Methyl-2,3-dihydro-1H-indole-5-carbonyl)-amino]-hexanedioic acid dimethyl ester (153304-72-4) → (S)-2-{[1-(2,4-Diamino-pteridin-6-ylmethyl)-7-methyl-2,3-dihydro-1H-indole-4-carbonyl]-amino}-hexanedioic acid dimethyl ester

Conditions	Yield
In N,N-dimethyl acetamide at 55 - 65℃; for 4h;	66%

4-amino-2-nitrobenzoic acid ethyl ester (84228-46-6) + 6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) → ethyl 4-{[(2,4-diaminopteridin-6-yl)methyl]amino}-2-nitrobenzoate (1355481-24-1)

Conditions	Yield
In N,N-dimethyl-formamide at 100℃; for 5h; Inert atmosphere;	66%

methyl 1-(4-amino-2-ethylbenzoyl)piperidine-4-carboxylate + 6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) → C23H28N8O3

Conditions	Yield
In N,N-dimethyl acetamide at 20℃; for 168h;	65%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + diethyl N-(indolin-5-carbonyl)-L-glutamate (142165-65-9) → diethyl N-[1-[(2,4-diamino-6-pteridinyl)methyl]indolin-5-carbonyl]-L-glutamate (142166-12-9)

Conditions	Yield
In N,N-dimethyl acetamide at 65℃; for 5h;	63%

6-bromomethyl-2,4-diaminopteridine hydrobromide (52853-40-4) + Nα-<4-(N-methylamino)benzoyl>-Nδ-<1,1-bis(diethylphosphono)methyl>glutamine benzyl ester → Nα-<4-amino-4-deoxy-N-10-methylpteroyl>-Nδ-<1,1-bis(diethylphosphono)methyl>glutamine benzyl ester

Conditions	Yield
In N,N-dimethyl acetamide at 50℃; for 4h;	62%

Upstream product

• 945-24-4 2,4-diamino-6-(hydroxymethyl)pteridine 
• 76145-91-0 2,4-diamino-6-hydroxymethylpteridine hydrobromide 
• 73978-41-3 2,4-diamino-6-(hydroxymethyl)pteridine hydrochloride 
• 60-29-7 diethyl ether 
• 37150-52-0 3-bromoacetonaldoxime 

Downstream Products

• 43111-51-9 ethyl 4-amino-4-deoxy-N¹⁰-methylpteroate 
• 36093-85-3 4-amino>benzoic acid 
• 272779-21-2 4-[2-(2,4-diamino-pteridin-6-yl)-1-methoxycarbonyl-1-methyl-ethyl]-benzoic acid methyl ester 
• 146464-91-7 methyl-4-(2-((2,4-diaminopteridin-6-yl)methyl)-1-methoxy-1-oxopent-4-yn-2-yl)benzoate 
• 947171-15-5 C₂₃H₃₀N₇PO₆ 
• 57963-46-9 6-(4-chloro-anilinomethyl)-pteridine-2,4-diamine 
• 59-05-2 N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid 
• 142166-28-7 methyl N^α-{1-[(2,4-diaminopteridin-6-yl)methyl]indolin-5-ylcarbonyl}-N^δ-(3-ethoxycarbonylphenyl)-L-glutaminate 
• 142166-24-3 methyl N^α-{1-[(2,4-diaminopteridin-6-yl)methyl]indolin-5-ylcarbonyl}-N^δ-phenyl-L-glutaminate 
• 154586-81-9 5-[1-Benzhydryloxycarbonyl-2-(2,4-diamino-pteridin-6-yl)-ethyl]-pyridine-2-carboxylic acid methyl ester 
• 72716-32-6 6-[(Triphenyl-λ⁵-phosphanylidene)-methyl]-pteridine-2,4-diamine 
• 82318-22-7 diethyl N-<4-<<(2,4-diamino-6-pteridinyl)methyl>octylamino>benzoyl>-L-glutamate 

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