14080-23-0

Basic information

• Product Name: 2-Cyanopyrimidine
• Synonyms: 2CPM;2-CPY;2-CYANOPYRIMIDINE;2-PYRIMIDINECARBONITRILE;PYRIMIDINE-2-CARBONITRILE;2-Cynopyrimidine;2-cyanpyrimidine;2-Pyrimidinecarbonitrile (6CI,7CI,8CI,9CI)
• CAS NO: 14080-23-0
• Molecular Formula: C₅H₃N₃
• Molecular Weight: 105.1
• EINECS: 1806241-263-5
• Product Categories: PYRIMIDINE;FINE Chemical & INTERMEDIATES;APIs & Intermediate;Pyridines, Pyrimidines, Purines and Pteredines;Pyrazines, Pyrimidines & Pyridazines;Pyrazines, Pyrimidines & Pyridazines;Building Blocks;Heterocyclic Building Blocks;Pyrimidines;Building Blocks;C4 to C5;Chemical Synthesis;Heterocyclic Building Blocks;Heterocycle-Pyrimidine series;cyanide
• Mol File: 14080-23-0.mol
• Article Data: 17

Chemical Properties

• Melting Point: 40-44 °C(lit.)
• Boiling Point: 250.7 °C at 760 mmHg
• Flash Point: >230 °F
• Appearance: White to yellow/Crystalline Powder
• Density: 1.22 g/cm³
• Vapor Pressure: 0.0214mmHg at 25°C
• Refractive Index: 1.54
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• Solubility: soluble in Methanol
• PKA: -3.27±0.13(Predicted)
• CAS DataBase Reference: 2-Cyanopyrimidine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Cyanopyrimidine(14080-23-0)
• EPA Substance Registry System: 2-Cyanopyrimidine(14080-23-0)

Safety Data

• Hazard Codes: Xn,C,F,T
• Statements: 22-37/38-41-43-34-11-25
• Safety Statements: 26-36/37/39-45-16-36/37
• RIDADR: 3276
• WGK Germany: 3
• HazardClass: IRRITANT
• PackingGroup: Ⅲ
• Hazardous Substances Data: 14080-23-0(Hazardous Substances Data)

Usage

Chemical Properties

White to yellow to brown solid

Biological Activity

2-cyano-pyrimidine is a cathepsin k inhibitor.cathepsin k is a protease defined by its high specificity for kinins, which is involved in bone resorption. cathepsin k's ability to catabolize collagen, elastin, and gelatin allow it to break down bone and cartilage. such catabolic activity is also partially responsible for the loss of lung elasticity and recoil in emphysema. therefore, inhibitors of cathepsin k are showing great potential in the treatment of osteoporosis.

in vitro

2-cyano-pyrimidine was identified as a cathepsin k inhibitor whose basic structure and derivatives have been evaluated for the treatment of osteoporosis. enzymatic study showed that 2-cyano-pyrimidine had an ic50 value of 170 nm for inhibition of cathepsin k, elevated activity of which has been linked to the formation of osteoporosis and arthritis. moreover, cathepsin k was found to be a lysosomal cysteine protease found in osteoclasts. [1,2].

IC 50

170 nm

references

[1] altmann, e. ,aichholz, r.,betschart, c., et al. 2-cyano-pyrimidines: a new chemotype for inhibitors of the cysteine protease cathepsin k. journal of medicinal chemistry 50(4), 591-594 (2007). [2] rankovic z et al. design and optimization of a series of novel 2-cyano-pyrimidines as cathepsin k inhibitors. bioorg med chem lett. 2010 mar 1;20(5):1524-7.

InChI:InChI=1/C5H3N3/c6-4-5-7-2-1-3-8-5/h1-3H

Synthetic route

tetraethylammoniumcyanide (13435-20-6) + N,N,N-trimethylpyrimidin-2-aminium chloride (14395-12-1) → 2-cyanopyrimidine (14080-23-0)

Conditions	Yield
In dichloromethane at 20℃; for 0.5h;	93%
In dichloromethane for 0.5h; Ambient temperature;	84%

2-chloropyrimidine (1722-12-9) + sodium cyanide (143-33-9) → 2-cyanopyrimidine (14080-23-0)

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane In dimethyl sulfoxide; isopropyl alcohol at 30 - 35℃; for 5h;	93%
In N,N-dimethyl-formamide at 60 - 70℃; for 24h;	49%
With trimethylamine In N,N-dimethyl-formamide at 25℃; for 66h; Product distribution; Thermodynamic data; ΔH, E(a); var. catalysts, solvents and times;	95 % Chromat.

2-chloropyrimidine (1722-12-9) + dicyanozinc (557-21-1) → 2-cyanopyrimidine (14080-23-0)

Conditions	Yield
With racemic 2-di-tert-butylphosphino-1,1'-binaphthyl; palladium(II) trifluoroacetate; zinc In N,N-dimethyl acetamide at 80℃; for 6h;	86.6%

2-chloropyrimidine (1722-12-9) + sodium cyanide (773837-37-9) → 2-cyanopyrimidine (14080-23-0)

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane In water; dimethyl sulfoxide	82%

2-chloropyrimidine (1722-12-9) + potassium cyanide (151-50-8) → 2-cyanopyrimidine (14080-23-0)

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane; water In dimethyl sulfoxide at 20℃; for 48h;	80%
With tetraethylammonium acetate In water; N,N-dimethyl-formamide at 90℃; for 48h;	27%

2-chloropyrimidine (1722-12-9) + potassium cyanide → 2-cyanopyrimidine (14080-23-0)

Conditions	Yield
With 3-quinuclidinol In dimethyl sulfoxide at 70℃; for 2.5h;	71%
With 1,4-diaza-bicyclo[2.2.2]octane In water; dimethyl sulfoxide at 20℃; for 48h;	65%
With 1,4-diaza-bicyclo[2.2.2]octane In dimethyl sulfoxide at 20℃; for 48h;

pyrimidine-2-diazonium o-benzenedisulfonimide + tetra-n-butylammonium cyanide (10442-39-4) → 2-cyanopyrimidine (14080-23-0)

Conditions	Yield
In acetonitrile at 22℃; for 1h; Sandmeyer Reaction;	69%

pyrimidin-2-carbaldehyde oxime (39232-40-1) → 2-cyanopyrimidine (14080-23-0)

Conditions	Yield
With Burgess Reagent In dichloromethane at 25℃; for 2h; Dehydration;	63%

2-chloropyrimidine (1722-12-9) + trimethylamine (75-50-3) → 2-cyanopyrimidine (14080-23-0)

Conditions	Yield
With benzene Erwaermen des Reaktionsprodukts mit KCN in Gegenwart von Acetamid;

2-chloropyrimidine (1722-12-9) → 2-cyanopyrimidine (14080-23-0)

Conditions	Yield
With sodium sulfite Erhitzen des Reaktionsprodukts mit KCN im Vakuum;
With 1,4-diaza-bicyclo[2.2.2]octane; sodium hydroxide In water; dimethyl sulfoxide
In water; dimethyl sulfoxide

pyrimidine-2-carboxamide (88511-48-2) → 2-cyanopyrimidine (14080-23-0)

Conditions	Yield
With trichlorophosphate

pyrimidine N-oxide (17043-94-6) + trimethylsilyl cyanide (7677-24-9) → 2-cyanopyrimidine (14080-23-0) + Pyrimidine-4-carbonitrile (42839-04-3)

Conditions	Yield
With triethylamine In acetonitrile for 0.17h; Heating; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

potassium cyanide (151-50-8) + N,N,N-trimethylpyrimidin-2-aminium chloride (14395-12-1) → 2-cyanopyrimidine (14080-23-0)

Conditions	Yield
With tetramethlyammonium chloride In dichloromethane; water at 25℃; for 2h; Yield given;

5-bromo-pyrimidine-2-carboxylic acid amide (38275-60-4) → 2-cyanopyrimidine (14080-23-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: Raney nickel; ethanol; diethyl ether / Hydrogenation.Reagens 4:wss.Na2CO3 2: POCl3 View Scheme

methyl 5-bromo-2-pyrimidinecarboxylate (89581-38-4) → 2-cyanopyrimidine (14080-23-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: methanol; NH3 2: Raney nickel; ethanol; diethyl ether / Hydrogenation.Reagens 4:wss.Na2CO3 3: POCl3 View Scheme

sodium cyanide (773837-37-9) + 2-bromopyrimidine (4595-60-2) → 2-cyanopyrimidine (14080-23-0)

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane In dimethyl sulfoxide at 20℃; for 1h;

pyrimidine-2-carbothioamide (4537-73-9) → 2-cyanopyrimidine (14080-23-0)

Conditions	Yield
With methylene blue; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 25℃; Sealed tube; Irradiation;	25.7 mg

2-cyanopyrimidine (14080-23-0) + sodium methylate (124-41-4) → methyl ester of imino-pyrimidine acid (57871-18-8)

Conditions	Yield
In methanol at 20℃; for 1h;	100%
In methanol
In methanol at 20℃;
In methanol

2-cyanopyrimidine (14080-23-0) → pyrimidine-2-carboxamidine hydrochloride

Conditions	Yield
With sodium methylate; ammonium chloride In methanol at 20℃; for 18h;	100%
Stage #1: 2-cyanopyrimidine With sodium methylate In methanol for 48h; Stage #2: With ammonium chloride In methanol for 24h;	84%
Stage #1: 2-cyanopyrimidine With sodium methylate In methanol at 20℃; for 24h; Stage #2: With ammonium chloride; acetic acid In methanol at 20℃; for 24h;	37.9%

2-cyanopyrimidine (14080-23-0) → pyrimidine-2-carboximidohydrazide (1005-03-4)

Conditions	Yield
With hydrazine hydrate In ethanol at 20℃; for 2h;	100%

2-cyanopyrimidine (14080-23-0) → pyrimidine-2-carboxamide (88511-48-2)

Conditions	Yield
With manganese(IV) oxide; water In isopropyl alcohol at 100℃; under 5171.62 Torr; for 0.05h; Catalytic behavior; Temperature;	99%
With cerium(IV) oxide; water at 30℃; for 3h;	92%
With C14H30ClN3PRh; water at 100℃; for 1h; Catalytic behavior; Inert atmosphere; Schlenk technique;	89%

2-cyanopyrimidine (14080-23-0) + ethanol (64-17-5) → 2-ethoxy pyrimidine (3739-82-0)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 80℃; for 2h;	98%

2-cyanopyrimidine (14080-23-0) + 2-methyl-propan-1-ol (78-83-1) → 2-isobutoxypyrimidine (10132-13-5)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 80℃; for 2h;	98%

2-cyanopyrimidine (14080-23-0) + 4-Methylbenzyl alcohol (589-18-4) → 2-[(4-methylbenzyl)oxy]pyrimidine

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 80℃; for 4h;	97%

2-cyanopyrimidine (14080-23-0) + 2-methylisothiourea sulphate (14527-26-5, 867-44-7) → 2-(methylsulfanyl)pyrimidine (823-09-6)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 80℃; for 2h;	97%

2-cyanopyrimidine (14080-23-0) + S-cyclopropylmethylisothiourea hydrobromide (63667-17-4) → 2-[(cyclopropylmethyl)thio]pyrimidine

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 80℃; for 4h;	97%

2-cyanopyrimidine (14080-23-0) + benzyl alcohol (100-51-6) → 2-(benzyloxy)pyrimidine (4214-64-6)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 80℃; for 5h; Solvent; Reagent/catalyst; Temperature;	96%

2-cyanopyrimidine (14080-23-0) + 2-phenylethanol (60-12-8) → 2-phenethoxypyrimidine

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 80℃; for 3h;	96%

2-cyanopyrimidine (14080-23-0) + Cyclopropylmethanol (2516-33-8) → 2-(cyclopropylmethoxy)pyrimidine

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 80℃; for 5h;	96%

2-cyanopyrimidine (14080-23-0) + C6H12N2S*BrH → 2-[(cyclobutylmethyl)thio]pyrimidine

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 80℃; for 4h;	96%

2-cyanopyrimidine (14080-23-0) + 2-pent-4-enyl-isothiourea; hydrobromide → 2-(pent-4-en-1-ylthio)pyrimidine

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 80℃; for 4h;	96%

2-cyanopyrimidine (14080-23-0) → 2-(1H-tetrazol-5-yl)pyrimidine (13600-33-4)

Conditions	Yield
With sodium azide; betaine; zinc(II) chloride In water at 20℃; for 20h;	95%
With sodium azide; water; zinc(II) chloride at 25℃; for 24h; Micellar solution;	88%
With sodium azide; zinc(II) chloride In water at 25℃; for 24h;	88%

2-cyanopyrimidine (14080-23-0) → 2-aminomethylpyrimidine (75985-45-4)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In ethanol under 760.051 Torr; for 12h; Inert atmosphere;	95%
With hydrogenchloride; palladium 10% on activated carbon; hydrogen In methanol; water at 20℃; for 3h;	44%
With hydrogen; Pd-C; ammonia In ethanol

pyrrolidine (123-75-1) + 2-cyanopyrimidine (14080-23-0) → 2-(pyrrolidine-1-yl)pyrimidine (192197-34-5)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 80℃; for 5h;	95%

Upstream product

• 1722-12-9 2-chloropyrimidine 
• 143-33-9 sodium cyanide 
• 39232-40-1 pyrimidin-2-carbaldehyde oxime 
• 38275-60-4 5-bromo-pyrimidine-2-carboxylic acid amide 
• 773837-37-9 sodium cyanide 
• 4595-60-2 2-bromopyrimidine 
• 4537-73-9 pyrimidine-2-carbothioamide 
• 10442-39-4 tetra-n-butylammonium cyanide 
• 89581-38-4 5-bromopyrimidine-2-carboxylic acid methyl ester 
• 557-21-1 dicyanozinc 
• 151-50-8 potassium cyanide 
• 14395-12-1 N,N,N-trimethylpyrimidin-2-aminium chloride 
• 13435-20-6 tetraethylammoniumcyanide 
• 17043-94-6 pyrimidine N-oxide 

Downstream Products

• 53342-27-1 2-acetylpyrimidine 
• 139584-77-3 2-<(prop-2-ynyloxy)carbonyl>pyrimidine 
• 88511-48-2 pyrimidine-2-carboxamide 
• 174812-98-7 2-pyrimidinyl(3-trifluoromethylphenyl)methanone 
• 13600-33-4 2-(1H-tetrazol-5-yl)pyrimidine 
• 562101-38-6 sodium pyrimidine-2-carboxylate 
• 57871-18-8 methyl ester of imino-pyrimidine acid 
• 1355176-97-4 N-isopropyl-4-(6-(pyrimidin-2-yl)-1,2,4,5-tetrazin-3-yl)benzamide 
• 1234687-35-4 4-(6-(pyrimidin-2-yl)-1,2,4,5-tetrazin-3-yl)benzoic acid 
• 753031-26-4 4,4′-(1,2,4,5-tetrazine-3,6-diyl)dibenzoic acid 
• 1146968-36-6 C₁₃H₁₀N₆O₂ 
• 53876-68-9 C₁₆H₁₂N₄O₄ 
• 1246834-64-9 2-aminomethylpyrimidine acetate 
• 42839-09-8 2-pyrimidinemethanol 

Relevant articles and documents

Synthesis and magnetic properties of a 4-(2′-pyrimidyl)-1,2,3,5- dithiadiazolyl dimanganese complex

A spin-bearing bis-bidentate ligand, designed from a pyrimidyl-substituted R-CN2S2 neutral radical, is used to co-ordinate two Mn(ii) metal centres yielding a thermally stable complex with antiferromagnetic coupling between the ligand-centred spin and the metal-centred spins, and thus an overall ferrimagnetic coupling scheme with a ground state S = 9/2. The Royal Society of Chemistry 2006.

Metal-free dehydrosulfurization of thioamides to nitriles under visible light

A visible light-mediated, metal-free dehydrosulfurization reaction of thioamides to nitriles is described. This reaction features high yields, mild reaction conditions, and the use of a cheap organic dye as the photoredox catalyst and air as the oxidant.

Electron-deficient heteroarenium salts: An organocatalytic tool for activation of hydrogen peroxide in oxidations

A series of monosubstituted pyrimidinium and pyrazinium triflates and 3,5-disubstituted pyridinium triflates were prepared and tested as simple catalysts of oxidations with hydrogen peroxide, using sulfoxidation as a model reaction. Their catalytic efficiency strongly depends on the type of substituent and is remarkable for derivatives with an electron-withdrawing group, showing reactivity comparable to that of flavinium salts which are the prominent organocatalysts for oxygenations. Because of their high stability and good accessibility, 4-(trifluoromethyl)pyrimidinium and 3,5-dinitropyridinium triflates are the catalysts of choice and were shown to catalyze oxidation of aliphatic and aromatic sulfides to sulfoxides, giving quantitative conversions, high preparative yields and excellent chemoselectivity. The high efficiency of electron-poor heteroarenium salts is rationalized by their ability to readily form adducts with nucleophiles, as documented by low pKR+ values (pKR+ red > -0.5 V). Hydrogen peroxide adducts formed in situ during catalytic oxidation act as substrate oxidizing agents. The Gibbs free energies of oxygen transfer from these heterocyclic hydroperoxides to thioanisole, obtained by calculations at the B3LYP/6-311++g(d,p) level, showed that they are much stronger oxidizing agents than alkyl hydroperoxides and in some cases are almost comparable to derivatives of flavin hydroperoxide acting as oxidizing agents in monooxygenases.

IMIDAZOTRIAZINONE COMPOUNDS

The present invention provides imidazotriazinone compounds which are inhibitors of phosphodiesterase 9 and pharmaceutically acceptable salt thereof. The present invention further provides processes, pharmaceutical compositions, pharmaceutical preparations and pharmaceutical use of the compounds in the treatment of PDE9 associated diseases or disorders in mammals, including humans.