4,6-Dichloro-5-methoxypyrimidine

• CAS: 5018-38-2
• Catalog Number: ACM5018382
• Category: Main Products
• Molecular Weight: 179.00
• Molecular Formula: C₅H₄Cl₂N₂O
• Synonyms: 4.6-Dichlor-5-methoxy-pyrimidin; Pyrimidine,4,6-dichloro-5-methoxy; 2,4-dimethoxy-2-methylmercapyrimidine; 5-Methoxy-4,6-dichloropyriMidine; 4,6-Dichloro-5-Methoxypyrimidine; 2,4-Dichloro-5-MetoxyPyriMidine; 4,6-dichloro-5-methoxy-pyrimidine; 2,4-Dichloro-5-methoxypyrimidine
• IUPAC Name: 4,6-dichloro-5-methoxypyrimidine
• SMILES: COC1=C(N=CN=C1Cl)Cl
• InChI Key: IJQIGKLDBGKSNT-UHFFFAOYSA-N
• Boiling Point: 257.8ºC at 760 mmHg
• Melting Point: 66-68ºC
• Flash Point: 109.7ºC
• Density: 1.446 g/cm³
• Appearance: yellow to light brown powder or light brown lumps
• EC Number: 225-699-1
• Exact Mass: 177.97000
• Hazard Statements: Xi

Case Study

4,6-Dichloro-5-methoxypyrimidine Used in the Synthesis of Influenza Endonuclease Inhibitors

Sagong, Hye Yeon, et al. Journal of medicinal chemistry 57.19 (2014): 8086-8098.

In this example, 4,6-dichloro-5-methoxypyrimidine was used as the central starting building block to access aza-heterocyclic scaffolds that were evaluated as inhibitors of influenza A endonuclease. The short sequence converted the dichloro-methoxypyrimidine into regio-functionalized derivatives amenable to Suzuki coupling and subsequent transformation to the active hydroxypyrimidinone motif.
· Selective methoxylation of one chloro: Treatment of 4,6-dichloro-5-methoxypyrimidine with sodium methoxide in methanol (cooled to 0 °C, then warmed to room temperature) converted the material to 4-chloro-5,6-dimethoxypyrimidine after 19 h. The product was isolated after solvent removal, extraction and silica gel flash chromatography (0 → 10% EtOAc/hexane) in 57% yield (168 mg from 300 mg starting material). This step demonstrates regioselective nucleophilic substitution on the dichloro intermediate to install an additional methoxy handle for downstream manipulation.
· Aryl installation by Suzuki coupling: The dimethoxy intermediate was engaged in a Suzuki cross-coupling with 4-fluorophenylboronic acid to introduce the aryl motif; this delivered 6-(4-fluorophenyl)-4,5-dimethoxypyrimidine (as reported). The arylation step establishes the phenyl substitution pattern required for the endonuclease inhibitor series.
· Hydrolysis to pyrimidinone and demethylation: Acidic hydrolysis (dioxane/2 N HCl, 1:1) converted the dimethoxy derivative to 5-methoxy-6-(4-fluorophenyl)pyrimidin-4(3H)-one, and a subsequent demethylation using BBr3 in CH2Cl2 removed the remaining methoxy to furnish the 5-hydroxy-2-(4-fluorophenyl)pyrimidin-4(3H)-one target used in biological evaluation.

4,6-Dichloro-5-Methoxypyrimidine: Key Building Block for Pyrimido[5,4-b][1,4]oxazine GPR119 Agonists

Fang, Yuanying, et al. Journal of Enzyme Inhibition and Medicinal Chemistry 35.1 (2020): 50-58.

This work optimized a series of pyrimido[5,4-b][1,4]oxazine derivatives as potent GPR119 agonists for potential treatment of type-2 diabetes. The heteroaromatic fragment 4,6-dichloro-5-methoxypyrimidine was used as the strategic electrophilic starting material to introduce the pyrimidine nucleus and enable downstream formation of the bicyclic oxazine core and diverse C-N substitution at the 4-position. Target molecules from this series (notably compounds 10 and 15) showed strong in-vitro potency (EC50 ≈ 13 and 12 nM) and in vivo glucose-lowering activity (compound 15 reduced blood-glucose AUC_0-2h by 23.4% at 30 mg/kg, compared with 17.9% for vildagliptin).
Synthesis Procedures:
· N-arylation: 4,6-Dichloro-5-methoxypyrimidine was reacted with 4-amino-3-fluorobenzonitrile in DMF with K2CO3 at 65 °C overnight, then extracted and purified by silica gel to give the aryl-amino pyrimidine.
· Demethylation: The methoxy group was removed by treating the aryl-amino intermediate with BBr3 in CH2Cl2 (reflux, 2 h), followed by workup and column chromatography to afford the 5-hydroxy pyrimidinone precursor.
· Cyclization: The 5-hydroxy intermediate was alkylated with 1-bromo-2-chloroethane in DMF with K2CO3 at 40 °C overnight, and the product was isolated by extraction and silica gel purification to furnish the bicyclic oxazine precursor.
· Buchwald-Hartwig diversification: The oxazine intermediate was coupled with various amines using Pd2(dba)3/X-Phos and Cs2CO3 in 1,4-dioxane (reflux, N2, overnight), then worked up and purified to yield the final series of target GPR119 agonists (representative compound 10 was obtained as a yellowish solid in 52% yield).

Custom Q&A

What is the molecular formula of 4,6-Dichloro-5-methoxypyrimidine?

The molecular formula is C5H4Cl2N2O.

What are the synonyms for 4,6-Dichloro-5-methoxypyrimidine?

The synonyms for 4,6-Dichloro-5-methoxypyrimidine are:
Pyrimidine, 4,6-dichloro-5-methoxy-
4,6-dichlor-5-methoxypyrimidin
4,6-dichloro-5-methoxy-pyrimidine
4,6-Dichloro-5-methoxy pyrimidine, etc.

What is the CAS number of 4,6-Dichloro-5-methoxypyrimidine?

The CAS number is 5018-38-2.

What is the IUPAC name of 4,6-Dichloro-5-methoxypyrimidine?

The IUPAC name is 4,6-dichloro-5-methoxypyrimidine.

What is the InChI of 4,6-Dichloro-5-methoxypyrimidine?

The InChI is InChI=1S/C5H4Cl2N2O/c1-10-3-4(6)8-2-9-5(3)7/h2H,1H3.

What is the molecular weight of 4,6-Dichloro-5-methoxypyrimidine?

The molecular weight is 179.00g/mol.

How many hydrogen bond donor counts does 4,6-Dichloro-5-methoxypyrimidine have?

It has 0 hydrogen bond donor counts.

How many hydrogen bond acceptor counts does 4,6-Dichloro-5-methoxypyrimidine have?

It has 3 hydrogen bond acceptor counts.

How many rotatable bond counts does 4,6-Dichloro-5-methoxypyrimidine have?

It has 1 rotatable bond count.

Is 4,6-Dichloro-5-methoxypyrimidine a canonicalized compound?

Yes, it is a canonicalized compound.