4241-27-4

Basic information

• Product Name: 3-Cyano-6-methyl-2(1H)-pyridinone
• Synonyms: 3-Cyano-6-methyl-2(1H)-pyridinone;2-keto-6-methyl-1H-pyridine-3-carbonitrile;Nicotinonitrile, 1,2-dihydro-6-methyl-2-oxo- (8CI);3-CYANO-6-METHYL-2(1H)-PYRIDINONE;3-CYANO-6-METHYL-2-PYRIDONE;3-CYANO-2-HYDROXY-6-METHYLPYRIDINE;6-METHYL-3-CYANO-2-PYRIDONE;6-METHYL-2-OXO-1,2-DIHYDROPYRIDINE-3-CARBONITRILE
• CAS NO: 4241-27-4
• Molecular Formula: C₇H₆N₂O
• Molecular Weight: 134.14
• EINECS: 224-202-5
• Product Categories: Boron, Nitrile, Thio,& TM-Cpds;Heterocycles;Pyridine;Building Blocks;C6 to C7;Chemical Synthesis;Heterocyclic Building Blocks;Pyridines;cyanide|alcohol
• Mol File: 4241-27-4.mol

Chemical Properties

• Melting Point: 293-295 °C
• Boiling Point: 247.23°C (rough estimate)
• Flash Point: 160.3 °C
• Appearance: SLIGHTLY YELLOW GRANULAR CRYSTALLINE POWDER
• Density: 1.2296 (rough estimate)
• Vapor Pressure: 0.00118mmHg at 25°C
• Refractive Index: 1.5880 (estimate)
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 9.03±0.10(Predicted)
• Water Solubility: 2.38 g/L (20 ºC)
• BRN: 120412
• CAS DataBase Reference: 3-Cyano-6-methyl-2(1H)-pyridinone(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Cyano-6-methyl-2(1H)-pyridinone(4241-27-4)
• EPA Substance Registry System: 3-Cyano-6-methyl-2(1H)-pyridinone(4241-27-4)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 36/37/38-20/21/22
• Safety Statements: 36/37/39-26-22-36
• RIDADR: 3276
• WGK Germany: 3
• TSCA: Yes
• HazardClass: IRRITANT
• PackingGroup: III
• Hazardous Substances Data: 4241-27-4(Hazardous Substances Data)

Usage

Chemical Properties

SLIGHTLY YELLOW GRANULAR CRYSTALLINE POWDER

Uses

3-Cyano-6-methyl-2(1H)-pyridinone is a reactant used in the synthesis of Milrinone (M344680), a selective phosphodiesterase inhibitor with vasodilating and positive inotropic activity. 3-It has also been used in the preparation of the N3?-pyridyl thiamine, a potent in vitro thiamine antagonist.

General Description

Supramolecular structures of coordination copper(I) compounds of 3-cyano-6-methyl-2(1H)-pyridinone has been investigated.

InChI:InChI=1/C7H6N2O/c1-9-4-2-3-6(5-8)7(9)10/h2-4H,1H3

Synthetic route

4-chloro-1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (582300-58-1) → 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4)

Conditions	Yield
With hydrogen; palladium on activated charcoal In methanol at 20℃;	88%

acetylacetaldehyde dimethyl acetal (5436-21-5) + cyanoacetic acid amide (107-91-5) → 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4)

Conditions	Yield
With piperdinium acetate In water for 24h; Reflux;	87.4%
With piperidinyl acetate at 80℃; for 24h;	80%
With piperdinium acetate at 80℃; for 24h;	73%

3-oxo-butyraldehyde; sodium enolate (41125-09-1, 14975-15-6, 926-59-0) + cyanoacetic acid amide (107-91-5) → 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4)

Conditions	Yield
With piperdinium acetate at 100℃; for 2h;	75%

acetone (67-64-1) + cyanoacetic acid amide (107-91-5) + formic acid ethyl ester (109-94-4) → 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4)

Conditions	Yield
Stage #1: acetone; formic acid ethyl ester With sodium methylate In tetrahydrofuran at 0 - 20℃; for 2h; Stage #2: cyanoacetic acid amide With piperidine; acetic acid In tetrahydrofuran; water for 2h; Reflux;	61%
Stage #1: acetone; formic acid ethyl ester With sodium In diethyl ether at 20℃; Cooling with ice; Stage #2: cyanoacetic acid amide In diethyl ether at 20℃; for 0.1h; Stage #3: With piperidine; water; acetic acid In diethyl ether for 2h; Reflux;	58%
Stage #1: acetone; formic acid ethyl ester With sodium methylate In diethyl ether at 0 - 20℃; for 2h; Stage #2: cyanoacetic acid amide With piperdinium acetate In water for 2h; Heating / reflux;	49%

3-oxo-butyraldehyde; sodium (Z)-1-enolate (42731-40-8) + cyanoacetic acid amide (107-91-5) → 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4)

Conditions	Yield
With piperdinium acetate In water for 0.166667h; Cycloaddition; Heating;	58%

5-cyano-2-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid (101184-51-4) → 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4)

Conditions	Yield
With copper In quinoline for 3h; Heating;	57%

1-cyanoformamide (4370-12-1) + acetylacetaldehyde dimethyl acetal (5436-21-5) → 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4)

Conditions	Yield
With piperdinium acetate for 24h; pH=9.5; Heating;	57%

piperidine (110-89-4) + cyanoacetic acid amide (107-91-5) + formic acid ethyl ester (109-94-4) → 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4)

Conditions	Yield
With sodium methylate; piperdinium acetate; acetic acid In diethyl ether; water; acetone	49%
With sodium methylate; piperdinium acetate; acetic acid In diethyl ether; water; acetone	49%
With sodium methylate; piperdinium acetate; acetic acid In diethyl ether; water; acetone	49%
With sodium methylate; piperdinium acetate; acetic acid In diethyl ether; water; acetone	49%

4-Ethoxy-4-hydroxy-butan-2-one + cyanoacetic acid amide (107-91-5) → 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4)

Conditions	Yield
In water for 2h; Heating; Yield given;

2-amino-6-methyl-4-oxo-4H-pyran-3-carbonitrile (67643-16-7) → 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 87 percent / HCl / H2O / 4 h / Heating 2: 75 percent / POCl3; PCl5 / CHCl3 / 6 h / Heating 3: 88 percent / H2 / Pd-C / methanol / 20 °C View Scheme

4-hydroxy-6-methyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile (67643-17-8) → 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 75 percent / POCl3; PCl5 / CHCl3 / 6 h / Heating 2: 88 percent / H2 / Pd-C / methanol / 20 °C View Scheme

5-Cyano-2-methyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid ethyl ester (52600-52-9) → 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 98 percent / KOH / aq. ethanol / 4 h / Heating 2: 57 percent / copper powder / quinoline / 3 h / Heating View Scheme

piperidine (110-89-4) + P2 O5 + potassium carbonate (584-08-7) + cyanoacetic acid amide (107-91-5) + formic acid ethyl ester (109-94-4) → 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4)

Conditions	Yield
With sodium methylate In water; acetic acid; acetone

trans-4-methoxy-3-buten-2-one (51731-17-0) + cyanoacetic acid amide (107-91-5) → 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4)

Conditions	Yield
In 2-methoxy-ethanol; water; acetic acid

1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) → 2-chloro-6-methylnicotinonitrile (28900-10-9)

Conditions	Yield
With trichlorophosphate at 130℃; for 2h; Inert atmosphere;	99%
With trichlorophosphate at 80 - 90℃; for 2.5h;	94%
With trichlorophosphate In 1,4-dioxane at 80℃; for 1h;	77%

1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) + thiourea (17356-08-0) → 4-amino-7-methyl-1H-pyrido[2,3-d]pyrimidine-2-thione

Conditions	Yield
With iodine In water for 1h;	96%

1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) → C7H10N2O*ClH

Conditions	Yield
Stage #1: 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile With ammonium hydroxide; nickel In methanol at 50℃; Inert atmosphere; Stage #2: With hydrogenchloride In ethyl acetate for 0.5h; Cooling with ice;	93.5%

1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) → 5-bromo-6-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (84725-13-3)

Conditions	Yield
With N-Bromosuccinimide In 1,2-dichloro-ethane Heating;	92%
With N-Bromosuccinimide In 1,2-dichloro-ethane for 18h; Reflux;	92.3%
With N-Bromosuccinimide In 1,2-dichloro-ethane at 85℃; for 7h;	91%

1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) → 6-Methylpyrid-2-one-3-carboxylic Acid (38116-61-9)

Conditions	Yield
With sodium hydroxide at 140℃; for 24h; pressure vessel;	85%
In sodium hydroxide	81%
In sodium hydroxide	81%

1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) → 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarboxaldehyde (78440-89-8)

Conditions	Yield
Stage #1: 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile With 1,1,1,3,3,3-hexamethyl-disilazane In toluene at 120℃; for 2h; Inert atmosphere; Stage #2: With diisobutylaluminium hydride In toluene at 0℃; for 9h; Inert atmosphere;	85%
Stage #1: 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile With 1,1,1,3,3,3-hexamethyl-disilazane In toluene for 2h; Inert atmosphere; Heating; Stage #2: With diisobutylaluminium hydride In toluene at 0℃; Inert atmosphere;	82%
With hydrogenchloride; diisobutylaluminium hydride; 1,1,1,3,3,3-hexamethyl-disilazane 1) toluen, refl. 3 hrs., 2) -42 deg C, 6 hrs.; Yield given. Multistep reaction;

trimethoxonium tetrafluoroborate (420-37-1) + 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) → 2-methoxy-6-methylpyridine-3-carbonitrile (72918-03-7)

Conditions	Yield
In dichloromethane for 48h; Ambient temperature;	83%

1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) → 1,2-dihydro-6-<(hydroxyimino)methyl>-2-oxo-3-pyridinecarbonitrile (343867-99-2)

Conditions	Yield
With n-Butyl nitrite; ammonia; potassium amide In diethyl ether for 1h;	80%

1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) + 4-bromobutanenitrile (5332-06-9) → 2-(3-cyanopropoxy)-6-methylpyridine-3-carbonitrile (174895-32-0)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80 - 90℃; for 2h;	76%

benzyl chloride (100-44-7) + 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) → 2-(benzyloxy)-6-methylnicotinonitrile (84647-23-4)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; zinc(II) oxide; zinc(II) chloride In 1,4-dioxane at 110℃; Inert atmosphere;	73%

1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) → 2-bromo-6-methylpyridine-3-carbonitrile (155265-57-9)

Conditions	Yield
With phosphorus pentaoxide; sodium bicarbonate; sodium chloride; tetrabutylammomium bromide In water; toluene	72.5%
With phosphorus pentoxide; tetrabutylammomium bromide In toluene for 5h; Reflux;

2-Methyl-1-phenyl-2-propanol (100-86-7) + 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) → C17H18N2O (1072954-70-1)

Conditions	Yield
With sulfuric acid In benzene at 60 - 70℃; for 0.5h;	72%

1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) + phenylmagnesium bromide (100-58-3) → 3-Benzoyl-6-methyl-2-oxopyridine (36228-62-3)

Conditions	Yield
In diethyl ether for 4h; Heating;	68%

1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) + cyclopentylmagnesium bromide (33240-34-5) → 3-Cyclopentanecarbonyl-6-methyl-1H-pyridin-2-one

Conditions	Yield
In diethyl ether for 4h; Heating;	63%

1-bromo-butane (109-65-9) + 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) → 6-Butyl-3-cyano-2-pyridone (118420-86-3)

Conditions	Yield
Stage #1: 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile With n-butyllithium; diisopropylamine In tetrahydrofuran; hexanes at -50 - 43℃; for 2.25h; Stage #2: 1-bromo-butane In tetrahydrofuran; hexanes at -50 - 25℃; for 1h;	61%

1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) + 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (572-09-8) → 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-3-cyano-6-methylpyridin-2-one (255391-45-8)

Conditions	Yield
With potassium hydroxide In water; acetone at 20℃; Condensation;	57%

1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) + allyl bromide (106-95-6) → 1-allyl-6-methyl-2-oxo-1,2-dihydro-pyridine-3-carbonitrile (641621-30-9)

Conditions	Yield
With sodium hydride; lithium bromide In 1,2-dimethoxyethane; N,N-dimethyl-formamide at 0 - 65℃;	57%

1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) + bromoacetic acid methyl ester (96-32-2) → methyl 2-((3-cyano-6-methylpyridin-2-yl)oxy)acetate + methyl 2-(3-cyano-6-methyl-2-oxopyridin-1(2H)-yl)acetate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide	A 31% B 56%

1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) + methyl iodide (74-88-4) → 3-cyano-6-ethyl-2(1H)-pyridinone (4241-20-7) + 6-isopropyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (5782-69-4)

Conditions	Yield
Stage #1: 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile With lithium diisopropyl amide In tetrahydrofuran at -78 - 0℃; for 2h; Stage #2: methyl iodide In tetrahydrofuran at 20℃; for 18h;	A 50% B 18%

methyl magnesium iodide (917-64-6) + 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) → 3-acetyl-6-methyl-2-(1H)pyridone (25957-23-7)

Conditions	Yield
In diethyl ether for 4h; Heating;	46%

1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) → 6-methyl-5-nitro-2-oxo-1,2-dihydropyridine-3-carbonitrile (85216-54-2)

Conditions	Yield
With sulfuric acid; nitric acid for 4h; Cooling with ice;	45%

di-tert-butyl dicarbonate (24424-99-5) + 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (4241-27-4) → (6-methyl-2-oxo-1,2-dihydropyridin-3-ylmethyl)carbamic acid tert-butyl ester

Conditions	Yield
With sodium tetrahydroborate; nickel dichloride In methanol at 0 - 20℃; for 15h;	35%