5355-16-8

Basic information

• Product Name: Diaveridine
• Synonyms: DIAVERIDIN;DIAVERIDINE;5-[(3,4-DIMETHOXYPHENYL)METHYL]-2,4-PYRIMIDINEDIAMINE;5-(3,4-DIMETHOXYBENZYL)-2,4-PYRIMIDINEDIAMINE;5-(3,4-DIMETHOXY-BENZYL)-PYRIMIDINE-2,4-DIAMINE;2,4-DIAMINO-5-(3,4-DIMETHOXY BENZYL)PYRIMIDINE;2,4-diamino-5-veratryl-pyrimidin;5-((3,4-dimethoxyphenyl)methyl)-4-pyrimidinediamine
• CAS NO: 5355-16-8
• Molecular Formula: C₁₃H₁₆N₄O₂
• Molecular Weight: 260.29
• EINECS: 226-333-3
• Mol File: 5355-16-8.mol
• Article Data: 9

Chemical Properties

• Melting Point: 233°
• Boiling Point: 506.104 °C at 760 mmHg
• Flash Point: 259.882 °C
• Appearance: /
• Density: 1.252 g/cm³
• Vapor Pressure: 2.29E-10mmHg at 25°C
• Refractive Index: 1.626
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly)
• PKA: 7.11±0.10(Predicted)
• Merck: 13,3017
• BRN: 258464
• CAS DataBase Reference: Diaveridine(CAS DataBase Reference)
• NIST Chemistry Reference: Diaveridine(5355-16-8)
• EPA Substance Registry System: Diaveridine(5355-16-8)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 2
• RTECS: UV8142000
• Hazardous Substances Data: 5355-16-8(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 5355-16-8 differently. You can refer to the following data:
1. Antibacterial.
2. Diaveridine is a dihydrofolate reductase inhibitor. It is used in veterinary medicine as a drug for its anticoccidial properties and its function as an antibacterial synergist.

Definition

ChEBI: An aminopyrimidine in which the pyrimidine ring carries amino substituents at C-2 and C-4 and a 3,4-dimethoxybenzyl group at C-5. A folic acid antagonist, it is used as a synergist with sulfonamides against the parasitic Eimeria species.

InChI:InChI=1/C13H16N4O2/c1-18-10-4-3-8(6-11(10)19-2)5-9-7-16-13(15)17-12(9)14/h3-4,6-7H,5H2,1-2H3,(H4,14,15,16,17)

Synthetic route

3-anilino-2-veratrylacrylonitrile (30077-75-9) + guanidine hydrochloride (50-01-1) → diaveridine (5355-16-8)

Conditions	Yield
With sodium methylate In ethanol for 24h; Heating;	96%

1,2-dimethoxybenzene (91-16-7) + pyrographite (7440-44-0) + 2,4-diamino-5-methoxymethylpyrimidine (54236-98-5) → diaveridine (5355-16-8)

Conditions	Yield
With potassium hydroxide; sodium hydroxide; phosphoric acid In water; acetic acid	88.7%

2-amino-5-veratryl-3H-pyrimidin-4-one (91959-82-9) → diaveridine (5355-16-8)

Conditions	Yield
With ethanol; ammonia; trichlorophosphate
With ethanol; ammonia; trichlorophosphate

guanidine nitrate (113-00-8) + (Z)-2-(3,4-Dimethoxy-benzyl)-3-morpholin-4-yl-acrylonitrile → diaveridine (5355-16-8)

Conditions	Yield
In ethanol; dimethyl sulfoxide

3,4-dimethoxy-benzaldehyde (120-14-9) → diaveridine (5355-16-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: Na-methylate / dimethylsulfoxide / 0.5 h / 65 - 75 °C 2: HCl cc. / propan-2-ol / 1 h / Heating 3: 96 percent / Na-methylate / ethanol / 24 h / Heating View Scheme

2-(3,4-dimethoxy-benzyl)-3-morpholin-4-yl-acrylonitrile (30077-88-4) → diaveridine (5355-16-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: HCl cc. / propan-2-ol / 1 h / Heating 2: 96 percent / Na-methylate / ethanol / 24 h / Heating View Scheme

β-morpholino-α-3,4,-dimethoxybenzylacrylonitrile → diaveridine (5355-16-8)

β-dimethylamino-α-3,4-dimethoxybenzylacrylonitrile → diaveridine (5355-16-8)

guanidine hydrochloride (50-01-1) + 2-(3,4-dimethoxy-benzyl)-3-morpholin-4-yl-acrylonitrile (30077-88-4) → diaveridine (5355-16-8)

Conditions	Yield
With sodium ethanolate In ethanol; dimethyl sulfoxide at 80℃; for 16h; Inert atmosphere;

diaveridine (5355-16-8) → 5-(4,5-dimethoxy-2-nitro-benzyl)-pyrimidine-2,4-diamine (91960-55-3)

Conditions	Yield
With water; nitric acid; acetic acid

diaveridine (5355-16-8) → 2,4-diamino-5-(3-methoxy-4-hydroxybenzyl)pyrimidine (73356-40-8)

Conditions	Yield
Stage #1: diaveridine With hydrogen bromide at 100℃; for 0.5h; Stage #2: With sodium hydroxide In water at 20℃;

diaveridine (5355-16-8) → C18H24N4O4

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydrogen bromide / 0.5 h / 100 °C 1.2: 20 °C 2.1: sodium hydride / N,N-dimethyl-formamide / 12 h / 20 °C View Scheme

diaveridine (5355-16-8) → C16H20N4O4

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydrogen bromide / 0.5 h / 100 °C 1.2: 20 °C 2.1: sodium hydride / N,N-dimethyl-formamide / 12 h / 20 °C 3.1: sodium hydroxide / methanol / 1 h / 55 °C / pH 4 - 5 View Scheme

Upstream product

• 91959-82-9 2-amino-5-veratryl-3H-pyrimidin-4-one 
• 30077-75-9 3-anilino-2-veratrylacrylonitrile 
• 50-01-1 guanidine hydrochloride 
• 30077-88-4 2-(3,4-dimethoxy-benzyl)-3-morpholin-4-yl-acrylonitrile 
• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 113-00-8 guanidine nitrate 
• 91-16-7 1,2-dimethoxybenzene 
• 7440-44-0 pyrographite 
• 54236-98-5 2,4-diamino-5-methoxymethylpyrimidine 

Downstream Products

• 73356-40-8 2,4-diamino-5-(3-methoxy-4-hydroxybenzyl)pyrimidine 

Relevant articles and documents

Halogenated trimethoprim derivatives as multidrug-resistant Staphylococcus aureus therapeutics

Incorporation of halogen atoms to drug molecule has been shown to improve its properties such as enhanced in membrane permeability and increased hydrophobic interactions to its target. To investigate the effect of halogen substitutions on the antibacterial activity of trimethoprim (TMP), we synthesized a series of halogen substituted TMP and tested for their antibacterial activities against global predominant methicillin resistant Staphylococcus aureus (MRSA) strains. Structure-activity relationship analysis suggested a trend in potency that correlated with the ability of the halogen atom to facilitate in hydrophobic interaction to saDHFR. The most potent derivative, iodinated trimethoprim (TMP-I), inhibited pathogenic bacterial growth with MIC as low as 1.25 μg/mL while the clinically used TMP derivative, diaveridine, showed resistance. Similar to TMP, synergistic studies indicated that TMP-I functioned synergistically with sulfamethoxazole. The simplicity in the synthesis from an inexpensive starting material, vanillin, highlighted the potential of TMP-I as antibacterial agent for MRSA infections.

Synthesis and antimycobacterial effects of some lipophilic substituted 2,4-diamino-5-benzylpyrimidines

2,4-Diamino-5-benzylpyrimidines 1-23 with lipophilic substitution in the benzylic moiety were synthesized by the morpholino-anilino-procedure. Their effects against various mycobacteria were verified by MIC (minimum inhibitory concentration) in whole cells and I50-measurements in whole cell and cell-free systems. Especially the substances 7-12 are strong inhibitors of some atypical mycobacterial strains which are sometimes associated with tuberculosis in the elderly and with AIDS. They might be promising candidates for therapy.

Benzyl cyanoacetals

Benzyl cyanoacetals of formula: STR1 wherein R1, R2 and R3 are the same or different and each is a halogen or a hydrogen atom, an alkoxy group, an alkyl group, or a dialkylamino group; R4 is an alkoxycarbonyl group, or an aldehyde group; And R5 is an alkyl group; the alkyl or alkoxy groups each having from 1 to 4 carbon atoms, and their use as intermediates in the preparation of antibacterial 2,4-diamino-5-benzylpyrimidines. They are prepared from a reaction between an orthoester and an α-substituted-β-benzylpropionitrile and then the resulting cyanoacetal is converted to the benzyl-pyrimidine by reaction with guanidine.