698-29-3

Basic information

• Product Name: 4-AMINO-2-METHYLPYRIMIDINE-5-CARBONITRILE
• Synonyms: 4-AMINO-2-METHYLPYRIMIDINE-5-CARBONITRILE;4-AMINO-5-CYANO-2-METHYLPYRIMIDINE;BUTTPARK 27\08-63;5-Pyrimidinecarbonitrile, 4-amino-2-methyl- (6CI,7CI,8CI,9CI);2-Methyl-4-aminopyrimidine-5-carbonitrile;4-Amino-2-methylpyrimidine-5-carbonitrile 98%;5-Cyano-4-aMino-2-MethylpyriMidine;NSC 459
• CAS NO: 698-29-3
• Molecular Formula: C₆H₆N₄
• Molecular Weight: 134.14
• EINECS: 211-814-2
• Product Categories: PYRIMIDINE;Pyrazines, Pyrimidines & Pyridazines;Nucleotides and Nucleosides;Bases & Related Reagents;Nucleotides;Pyrazines, Pyrimidines & Pyridazines;Amines;Aromatics;Heterocycles
• Mol File: 698-29-3.mol
• Article Data: 24

Chemical Properties

• Melting Point: 249 °C
• Boiling Point: 315.6 °C at 760 mmHg
• Flash Point: 144.7 °C
• Appearance: Pale yellow/Powder
• Density: 1.27 g/cm³
• Storage Temp.: -20°C Freezer
• Solubility: DMSO, Ethanol, Methanol
• PKA: 3.00±0.10(Predicted)
• Water Solubility: Slightly soluble in water (6.4 g/L at 25°C). Soluble in dimethyl sulfoxide, ethanol and methanol.
• CAS DataBase Reference: 4-AMINO-2-METHYLPYRIMIDINE-5-CARBONITRILE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-AMINO-2-METHYLPYRIMIDINE-5-CARBONITRILE(698-29-3)
• EPA Substance Registry System: 4-AMINO-2-METHYLPYRIMIDINE-5-CARBONITRILE(698-29-3)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 22-37/38-41
• Safety Statements: 26-39
• HazardClass: IRRITANT
• Hazardous Substances Data: 698-29-3(Hazardous Substances Data)

Usage

Uses

4-Amino-5-cyano-2-methylpyrimidine is used as a pharmaceutical intermediate.

InChI:InChI=1/C6H6N4/c1-4-9-3-5(2-7)6(8)10-4/h3H,1H3,(H2,8,9,10)

Synthetic route

Trimethyl orthoacetate (1445-45-0) + 2-cyanoethylamine (151-18-8) + CYANAMID (420-04-2) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
Stage #1: Trimethyl orthoacetate; 2-cyanoethylamine In methanol at 50 - 55℃; for 2h; Stage #2: CYANAMID In methanol at 55 - 60℃; for 3h; Temperature; Solvent; Further stages;	98.1%

ethanimidamide hydrochloride + 1-(dimethylamine)-2,2-dicyanoethylene (16849-88-0) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
Stage #1: ethanimidamide hydrochloride With sodium methylate In methanol for 0.166667h; Cooling with ice; Stage #2: 1-(dimethylamine)-2,2-dicyanoethylene In methanol at 20℃; for 12.5h;	97%

2-cyanoethylamine (151-18-8) + CYANAMID (420-04-2) + triisopropyl orthoacetate (72858-79-8) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
Stage #1: 2-cyanoethylamine; triisopropyl orthoacetate In isopropyl alcohol at 50 - 55℃; for 2h; Stage #2: CYANAMID In isopropyl alcohol at 55 - 60℃; for 3h; Further stages;	93.3%

formaldehyd (50-00-0) + acetamidine hydrochloride (124-42-5) + malononitrile (109-77-3) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
Stage #1: formaldehyd; acetamidine hydrochloride; malononitrile In water; tert-butyl alcohol at 65 - 70℃; for 4h; Mannich Aminomethylation; Stage #2: With tert.-butylhydroperoxide In water; tert-butyl alcohol at 20 - 35℃; for 1h; Temperature; Solvent; Reagent/catalyst;	92.6%

2-cyanoethylamine (151-18-8) + CYANAMID (420-04-2) + Triethyl orthoacetate (78-39-7) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
Stage #1: 2-cyanoethylamine; Triethyl orthoacetate In ethanol at 50 - 55℃; for 2h; Stage #2: CYANAMID In ethanol at 55 - 60℃; for 3h; Further stages;	91.8%

1-(dimethylamine)-2,2-dicyanoethylene (16849-88-0) + acetamidine hydrochloride (124-42-5) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
Stage #1: acetamidine hydrochloride With sodium methylate In methanol for 0.166667h; Cooling with ice; Large scale reaction; Stage #2: 1-(dimethylamine)-2,2-dicyanoethylene In methanol at 20℃; for 12.5h; Cooling; Large scale reaction;	90%
With sodium methylate In methanol at 0℃; for 0.333333h; Product distribution / selectivity;	65%
With sodium methylate In methanol
With sodium acetate In methanol at 20℃;

ethanimidamide hydrochloride + Ethoxymethylenemalononitrile (123-06-8) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
Stage #1: ethanimidamide hydrochloride With sodium methylate In ethanol at 20℃; Stage #2: Ethoxymethylenemalononitrile In ethanol for 1h;	74.7%

acetamidine (143-37-3) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) + malononitrile (109-77-3) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
Stage #1: N,N-dimethyl-formamide With dimethyl sulfate at 70℃; for 3.5h; Stage #2: malononitrile With sodium methylate In methanol at -15℃; for 0.666667h; Stage #3: acetamidine In methanol at -15 - 20℃; for 15.5h;	69%

ethanimidamide hydrochloride + N,N-dimethyl-formamide (68-12-2, 33513-42-7) + malononitrile (109-77-3) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
Stage #1: N,N-dimethyl-formamide With dimethyl sulfate at 70℃; for 3.5h; Stage #2: With sodium methylate In methanol at -20 - -10℃; for 0.666667h; Stage #3: ethanimidamide hydrochloride; malononitrile Further stages;	69%

2-diethylaminomethylenemalononitrile (38238-93-6) + acetamidine hydrochloride (124-42-5) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
With sodium methylate In methanol at 0℃; for 0.333333h;	63%

2-(methoxymethylene)malononitrile (672-81-1) + acetamidine (143-37-3) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
Stage #1: acetamidine With sodium methylate In ethanol at 20℃; for 0.666667h; Stage #2: 2-(methoxymethylene)malononitrile	26%

2-methyl-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile (27058-54-4) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
With trichlorophosphate folgendes Erhitzen mit aethanol.NH3;
Multi-step reaction with 2 steps 1: POCl3 2: NH3 View Scheme

4-chloro-2-methylpyrimidine-5-carbonitrile (38875-74-0) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
With ammonia

2-methyl-4-amino-5-(carboxamidemethyl)pyrimidine (7389-14-2) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
With trichlorophosphate

4-ethoxy-2-methyl-pyrimidine-5-carbonitrile (874495-29-1) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
With ammonia

4-amino-6-chloro-2-methyl-5-pyrimidinecarbonitrile (76574-37-3) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
With methanol; Lindlar's catalyst Hydrogenation;

ethanol (64-17-5) + ethyl acetimidate hydrochloride (2208-07-3) + aminomethylene-malononitrile (672-25-3) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
Versetzen der Reaktionsloesungen mit alkoh.NaOH oder Natriumaethylat-Loesung;

thioacetimidic acid ethyl ester (3613-29-4) + aminomethylene-malononitrile (672-25-3) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

thioacetamide (62-55-5) + aminomethylene-malononitrile (672-25-3) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

iminomethyl-malononitrile + thioacetamide (62-55-5) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Triethyl orthoacetate (78-39-7) + aminomethylene-malononitrile (672-25-3) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

ethanol (64-17-5) + acetamidine (143-37-3) + Ethoxymethylenemalononitrile (123-06-8) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

acetamidine (143-37-3) + Ethoxymethylenemalononitrile (123-06-8) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

tetrachloromethane (56-23-5) + ethanol (64-17-5) + 2-cyano-3-imino-propionic acid ethyl ester + O-ethyl acetimidate (1000-84-6) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
Raumtemperatur;
Raumtemperatur;

O-ethyl acetimidate (1000-84-6) + Ethoxymethylenemalononitrile (123-06-8) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
With ammonia
With ammonia

O-ethyl acetimidate (1000-84-6) + aminomethylene-malononitrile (672-25-3) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

acetamidine hydrochloride (124-42-5) + Ethoxymethylenemalononitrile (123-06-8) → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
With sodium ethanolate 1) EtOH; 2) EtOH; Yield given. Multistep reaction;
With ethanol; sodium for 2h;
Stage #1: acetamidine hydrochloride With sodium ethanolate In ethanol at 20℃; for 1h; Stage #2: Ethoxymethylenemalononitrile In ethanol at 20℃; for 3h;

O-ethyl acetimidate (1000-84-6) + Ethoxymethylenemalononitrile (123-06-8) + alcoholic NH3 → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

ethyl acetimidate hydrochloride (2208-07-3) + Ethoxymethylenemalononitrile (123-06-8) + alcoholic NH3 → 2-methyl-4-amino-5-cyanopyrimidine (698-29-3)

Conditions	Yield
Versetzen der Reaktionsloesungen mit alkoh.NaOH oder Natriumaethylat-Loesung;

2-methyl-4-amino-5-cyanopyrimidine (698-29-3) → 5-(aminomethyl)-2-methylpyrimidin-4-amine (95-02-3)

Conditions	Yield
With ammonia; hydrogen In methanol at 70 - 100℃; under 14251.4 Torr; Reagent/catalyst; Temperature;	100%
With ammonia; hydrogen In methanol at 100℃; under 30003 Torr; for 5h; Autoclave; Saturated solution; Large scale reaction;	98%
With ammonia; hydrogen In methanol at 60℃; under 30003 Torr; for 24h; Autoclave;	90%

2-methyl-4-amino-5-cyanopyrimidine (698-29-3) + carbon dioxide (124-38-9) → 7-methyl-1H-pyrimido[4,5-d]pyrimidine-2,4-dione (112842-89-4)

Conditions	Yield
With 1,5-diazabicyclo[4.3.0]non-5-ene 2,2,2-trifluoroethanol at 90℃; for 48h;	85%
With 1,5-diazabicyclo[4.3.0]non-5-ene 2,2,2-trifluoroethanol at 90℃; under 760.051 Torr; for 48h; Green chemistry;	85%

2-methyl-4-amino-5-cyanopyrimidine (698-29-3) → 4-amino-2-methylpyrimidine-5-carbaldehyde (73-68-7)

Conditions	Yield
With formic acid; nickel In water for 0.25h; Reflux;	83%
With formic acid In water for 0.25h; Reflux;	83%
With sulfuric acid; palladium 10% on activated carbon; hydrogen In water at 20℃; for 16h;	70%

2-methyl-4-amino-5-cyanopyrimidine (698-29-3) → 4-amino-2-methylpyrimidine-5-carbaldehyde-d (173557-81-8)

Conditions	Yield
With lithium aluminium deuteride In tetrahydrofuran for 1.5h;	28%

formic acid (64-18-6) + 2-methyl-4-amino-5-cyanopyrimidine (698-29-3) → 4-amino-2-methylpyrimidine-5-carbaldehyde (73-68-7)

Conditions	Yield
nickel at 80 - 100℃; for 0.75h;	20%

ethyl 2-hydroxypropionate (97-64-3, 2676-33-7) + 2-methyl-4-amino-5-cyanopyrimidine (698-29-3) → N-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-lactamide

Conditions	Yield
With kieselguhr; ethanol; nickel at 140 - 150℃; Hydrogenation.unter Druck;

2-methyl-4-amino-5-cyanopyrimidine (698-29-3) + formamide (77287-34-4, 77287-35-5, 60100-09-6) → 7-methyl-pyrimido[4,5-d]pyrimidin-4-ylamine (118801-92-6)

2-methyl-4-amino-5-cyanopyrimidine (698-29-3) + formamide (77287-34-4, 77287-35-5, 60100-09-6) → 2-methyl-4-amino-5-formylaminomethylpyrimidine (1886-34-6)

Conditions	Yield
With nickel at 130 - 150℃; under 36775.4 - 73550.8 Torr; Hydrogenation;

2-methyl-4-amino-5-cyanopyrimidine (698-29-3) + formamide (77287-34-4, 77287-35-5, 60100-09-6) → (4-amino-2-methyl-pyrimidin-5-ylmethyl)-(4-amino-2-methyl-pyrimidin-5-ylmethylen)-amine (108482-83-3) + 2-methyl-4-amino-5-formylaminomethylpyrimidine (1886-34-6)

Conditions	Yield
With ethanol at 150℃; Hydrogenation;

2-methyl-4-amino-5-cyanopyrimidine (698-29-3) + guanidine nitrate (113-00-8) → 4,6-bis-(4-amino-2-methyl-pyrimidin-5-yl)-[1,3,5]triazin-2-ylamine

Conditions	Yield
With ethanol

2-methyl-4-amino-5-cyanopyrimidine (698-29-3) + formic acid ethyl ester (109-94-4) → 2-methyl-4-amino-5-formylaminomethylpyrimidine (1886-34-6)

Conditions	Yield
With nickel at 130 - 150℃; under 36775.4 - 73550.8 Torr; Hydrogenation;

2-methyl-4-amino-5-cyanopyrimidine (698-29-3) + formic acid ethyl ester (109-94-4) → (4-amino-2-methyl-pyrimidin-5-ylmethyl)-(4-amino-2-methyl-pyrimidin-5-ylmethylen)-amine (108482-83-3) + 2-methyl-4-amino-5-formylaminomethylpyrimidine (1886-34-6)

Conditions	Yield
With nickel at 150℃; Hydrogenation;

2-methyl-4-amino-5-cyanopyrimidine (698-29-3) → 2-methyl-4-amino-5-hydroxymethylpyrimidine (73-67-6)

Conditions	Yield
With hydrogenchloride; palladium; acetic acid Hydrogenation;
Multi-step reaction with 2 steps 1: 20 percent / Raney Ni / 0.75 h / 80 - 100 °C 2: 93 percent / NaBH4 / methanol / 0.5 h / Ambient temperature View Scheme

2-methyl-4-amino-5-cyanopyrimidine (698-29-3) → 2-methyl-4-amino-5-(carboxamidemethyl)pyrimidine (7389-14-2)

Conditions	Yield
With sulfuric acid
With dihydrogen peroxide

2-methyl-4-amino-5-cyanopyrimidine (698-29-3) → 4-amino-2-methyl-pyrimidine-5-carbothioic acid amide (82302-19-0)

Conditions	Yield
With hydrogen sulfide
With pyridine; hydrogen sulfide; triethylamine In N-methyl-acetamide

2-methyl-4-amino-5-cyanopyrimidine (698-29-3) → 4-amino-2-methylpyrimidine-5-carboxylic acid (769-52-8)

Conditions	Yield
With potassium hydroxide
With sodium hydroxide
With water; potassium hydroxide

2-methyl-4-amino-5-cyanopyrimidine (698-29-3) → (4-amino-2-methyl-pyrimidin-5-ylmethyl)-(4-amino-2-methyl-pyrimidin-5-ylmethylen)-amine (108482-83-3)

Conditions	Yield
With nickel Hydrogenation;
Multi-step reaction with 2 steps 1: Raney nickel / Hydrogenation View Scheme

Upstream product

• 27058-54-4 2-methyl-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile 
• 78-39-7 Triethyl orthoacetate 
• 672-25-3 aminomethylene-malononitrile 
• 56-23-5 tetrachloromethane 
• 64-17-5 ethanol 
• 1000-84-6 O-ethyl acetimidate 
• 123-06-8 Ethoxymethylenemalononitrile 
• 19875-04-8 2-methyl-3H-pyrimidin-4-one 
• 40497-30-1 2-methyl-1H-pyrimidine-4,6-dione 
• 3613-29-4 thioacetimidic acid ethyl ester 
• 2208-07-3 ethyl acetimidate hydrochloride 
• 76574-37-3 4-amino-6-chloro-2-methyl-5-pyrimidinecarbonitrile 
• 874495-29-1 4-ethoxy-2-methyl-pyrimidine-5-carbonitrile 
• 7389-14-2 2-methyl-4-amino-5-(carboxamidemethyl)pyrimidine 

Downstream Products

• 1386981-61-8 (R)-tert-butyl 3-(4-chloro-3-(2-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-carboxamido)benzamido)-3-phenylpropylcarbamate 
• 769-52-8 4-amino-2-methylpyrimidine-5-carboxylic acid 
• 82302-19-0 4-amino-2-methyl-pyrimidine-5-carbothioic acid amide 
• 7389-14-2 2-methyl-4-amino-5-(carboxamidemethyl)pyrimidine 
• 95-02-3 5-(aminomethyl)-2-methylpyrimidin-4-amine 
• 108482-83-3 (4-amino-2-methyl-pyrimidin-5-ylmethyl)-(4-amino-2-methyl-pyrimidin-5-ylmethylen)-amine 
• 1886-34-6 2-methyl-4-amino-5-formylaminomethylpyrimidine 

Relevant articles and documents

Studies on the Thorpe-Ziegler-reaction. A new synthesis of the pyridine part of thiamine

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Fully continuous flow preparation method of 2-methyl-4-amino-5-aminomethylpyrimidine

The invention discloses a fully continuous flow preparation method of 2-methyl-4-amino-5-aminomethylpyrimidine. The method comprises the following steps: mixing a mixed solution of cyanoacetamide, N, N-dimethylformamide and a catalyst with phosphorus oxychloride in a micro-mixer, and carrying out a continuous flow reaction in a micro-channel reactor to obtain (dimethyl aminomethylene) malononitrile; continuously quenching, continuously extracting and separating, concentrating an organic solution, mixing with a methanol solution, and continuously reacting with organic alkali to obtain 2-methyl-4-amino-5-cyanopyrimidine; continuously filtering the reaction mixed solution, dissolving the solid with methanol, conveying the dissolved solid and hydrogen to a fixed bed microchannel reactor through a micromixer, carrying out hydrogenation reaction, and concentrating, drying and purifying the product to obtain the 2-methyl-4-amino-5-aminomethylpyrimidine product. The method is mild in reaction condition, short in reaction time, high in product yield, low in energy consumption, green, safe and easy to industrially amplify and apply.

Fully Continuous Flow Synthesis of 5-(Aminomethyl)-2-methylpyrimidin-4-amine: A Key Intermediate of Vitamin B1

Herein, we demonstrate an expeditiously fully continuous flow synthesis of 5-(aminomethyl)-2-methylpyrimidin-4-amine, a key intermediate for vitamin B1. The process is accomplished via three chemical transformations in six sequential continuous flow devices from an economical starting material, 2-cyanoacetamide. First, single step continuous flow synthesis is demonstrated in a certain type of flow reactor for each reaction step, with a yield of 94, 90, and 99%, respectively. Then, fully continuous flow synthesis of 5-(aminomethyl)-2-methylpyrimidin-4-amine is demonstrated in 84% total yield with a total residence time of 74 min and 0.92 g/h throughput.

Method for preparing 2-methyl-4-amino-5-cyanopyrimidine by Mannich reaction

The invention relates to a method for preparing 2-methyl-4-amino-5-cyanopyrimidine by Mannich reaction. According to the invention, ethylamidine hydrochloride, malononitrile and an aldehyde compound are used as raw materials and subjected to the Mannich reaction to obtain 2-methyl-4-amino-5-cyano-5,6-dihydropyrimidine hydrochloride that is then oxidized by an oxidizer to obtain the 2-methyl-4-amino-5-cyanopyrimidine. The raw materials malononitrile and ethylamidine hydrochloride used for the method for preparing 2-methyl-4-amino-5-cyanopyrimidine by Mannich reaction are high in stability under reaction conditions, thereby reducing side reactions of the malononitrile and free ethylamidine hydrochloride under an alkaline condition and providing guarantee for high yield and high purity of the product.