22536-65-8

Usage

Uses

Used in Pharmaceutical Industry:
2-Chloro-5-methoxypyrimidine is used as an intermediate in the synthesis of various pharmaceutical compounds. Its application is particularly significant in the regioselective synthesis of aminoimidazopyrimidines, which are important for the development of new drugs with potential therapeutic applications.
Used in Chemical Synthesis:
In the field of chemical synthesis, 2-Chloro-5-methoxypyrimidine serves as a key building block for creating a wide range of molecules with diverse properties and functions. Its reactivity and structural features make it a valuable component in the synthesis of various organic compounds, including those with potential applications in materials science, agrochemistry, and other industries.

InChI:InChI=1/C5H5ClN2O/c1-9-4-2-7-5(6)8-3-4/h2-3H,1H3

Synthetic route

2,4-dichloro-5-methoxypyrimidine (19646-07-2) → 2-chloro-5-methoxy-pyrimidine (22536-65-8)

Conditions	Yield
With water; zinc In ethanol for 4h; Reflux;	58%
With zinc In ethanol; water for 4h; Reflux;	58%
With acetic acid; zinc In ethanol Reflux; Large scale;	50 g

5-Methoxypyrimidine-2,4(1H,3H)-dione (6623-81-0) → 2-chloro-5-methoxy-pyrimidine (22536-65-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: trichlorophosphate; N,N-dimethyl-aniline / 2 h / Reflux 2: zinc; water / ethanol / 4 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: trichlorophosphate / N,N-dimethyl-aniline / 2 h / Reflux 2: zinc / ethanol; water / 4 h / Reflux View Scheme

2-chloro-5-methoxy-pyrimidine (22536-65-8) → 2‐hydrazinyl‐5‐methoxypyrimidine (34712-29-3)

Conditions	Yield
With hydrazine hydrate In ethanol at 60℃; for 24h;	96%

2-chloro-5-methoxy-pyrimidine (22536-65-8) → 2-chloropyrimidine-5-ol (4983-28-2)

Conditions	Yield
With hydrogen bromide; DL-methionine In acetic acid for 5h; Reflux;	91%
Stage #1: 2-chloro-5-methoxy-pyrimidine With boron tribromide In dichloromethane at 20℃; Stage #2: With sodium hydrogencarbonate In dichloromethane; water	62%
With boron tribromide In dichloromethane at 20℃; for 20h;	61%

1-Methylpyrrolidine (120-94-5) + phthalimide (136918-14-4) + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → C18H20N4O3

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 160℃; for 12h;	85%

tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate (375853-82-0, 286961-14-6) + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → tert-butyl 4-(5-methoxypyrimidin-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (1440954-81-3)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane at 140℃; for 0.25h; Microwave irradiation;	83%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane at 140℃; for 0.25h; Microwave irradiation;	83%

piperazine (110-85-0) + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → 5-methoxy-2-(1-piperazinyl)pyrimidine (59215-39-3)

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); 2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1′-biphenyl; caesium carbonate In 1,4-dioxane at 100℃; for 0.666667h;	78%
In isopropyl alcohol at 140℃; for 1h; Microwave irradiation;	32%

(R)-3-((tert-butoxycarbonyl)amino)-4-(5-(4-hydroxyphenyl)-2H-tetrazol-2-yl)butyric acid tert-butyl ester + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → tert-butyl (R)-3-((tert-butoxycarbonyl)amino)-4-(5-(4-((5-methoxypyrimidin-2-yl)oxy)phenyl)-2H-tetrazol-2-yl)butanoate

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 90℃; for 3h;	72%

1,4-diaza-bicyclo[2.2.2]octane (280-57-9) + potassium phtalimide (1074-82-4) + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → 2-(2-(4-(5-methoxypyrimidin-2-yl)piperazin-1-yl)ethyl)isoindoline-1,3-dione

Conditions	Yield
In N,N-dimethyl-formamide at 120℃; for 24h; Inert atmosphere;	71%

4-methyl-2,6-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → 4-methyl-2,6-bis(5-methoxypyrimidin-2-yl)aniline

Conditions	Yield
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; potassium carbonate In water; acetonitrile at 100℃; for 16h; Inert atmosphere; Sealed tube;	71%

N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl]carbamic acid 1,1-dimethylethyl ester (1095708-32-9) + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → 4-(5-methoxypyrimidin-2-yl)pyridin-2-amine

Conditions	Yield
With sodium hydrogencarbonate In 1,4-dioxane; water at 140℃; for 0.833333h; Inert atmosphere; Microwave irradiation;	70%

2-chloro-5-methoxy-pyrimidine (22536-65-8) + allylmagnesium bromide (1730-25-2) → C8H9ClN2O

Conditions	Yield
Stage #1: 2-chloro-5-methoxy-pyrimidine; allylmagnesium bromide In tetrahydrofuran at 0 - 20℃; for 0.25h; Stage #2: With 2,3-dicyano-5,6-dichloro-p-benzoquinone In 1,4-dioxane at 0℃;	69%

methanol (67-56-1) + carbon monoxide (201230-82-2) + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → methyl 5-methoxypyrimidine-2-carboxylate (1415800-40-6)

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine In N,N-dimethyl-formamide at 120℃; under 22502.3 Torr;	57%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine In acetonitrile at 20 - 100℃; Inert atmosphere;	52%
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine In acetonitrile at 100℃; for 18h; Autoclave;	52%

2-chloro-5-methoxy-pyrimidine (22536-65-8) → 5-methoxypyrimidin-2-amine (13418-77-4)

Conditions	Yield
With ammonia In water at 150℃; for 3h; Irradiation;	55%
With ammonium hydroxide at 100℃; for 18h; Sealed tube;	45%

2-chloro-5-methoxy-pyrimidine (22536-65-8) → 2-bromo-5-hydroxypyrimidine

Conditions	Yield
With boron tribromide In dichloromethane at -78 - 20℃;	54%

2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1609393-90-9) + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → 2-methoxy-3-(5-methoxypyrimidin-2-yl)aniline

Conditions	Yield
With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 105℃; for 20h; Suzuki Coupling; Sealed tube; Inert atmosphere;	54%

4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(3-methoxyphenoxy)-4-pyrimidinyl]benzenesulfonamide (150725-87-4) + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → 4-tert-butyl-N-{5-(3-methoxy-phenoxy)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-yl}-benzenesulfonamide

Conditions	Yield
With sodium hydride In N,N-dimethyl acetamide at 20℃; for 48h;	52%

ciprofloxacin (85721-33-1) + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → C22H22FN5O4

Conditions	Yield
With potassium carbonate In acetonitrile at 80℃; for 23h;	51.4%

1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid (70458-96-7) + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → C21H22FN5O4

Conditions	Yield
With potassium carbonate In acetonitrile at 80℃; for 24h;	50.3%

(-)-(5S)-4-(4,4-difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-2-(piperidin-4-yl)-5,6,7,8-tetrahydroquinoline (1354495-70-7) + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → (-)-(5S)-4-(4,4-difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-2-[1-(5-methoxypyrimidin-2-yl)piperidin-4-yl]-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol (1354494-79-3)

Conditions	Yield
Stage #1: (-)-(5S)-4-(4,4-difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-2-(piperidin-4-yl)-5,6,7,8-tetrahydroquinoline; 2-chloro-5-methoxy-pyrimidine In 1,4-dioxane at 80℃; for 26.6h; Stage #2: With hydrogenchloride In 1,4-dioxane; water at 50℃; for 8h; Stage #3: With sodium hydrogencarbonate In 1,4-dioxane; water	45%

4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazole + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → 2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-5-methoxypyrimidine

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 160℃; for 1h; Microwave irradiation;	45%
With caesium carbonate In acetonitrile at 160℃; for 1.5h; Microwave irradiation;	45%

4-benzyl-3-ethoxy-5-methyl-1H-pyrazole (1116655-96-9) + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → 2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-methoxypyrimidine

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 160℃; for 1h; Microwave irradiation;	44%

4-((4-bromo-2-fluorophenoxy)methyl)piperidine hydrochloride + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → 2-(4-((4-bromo-2-fluorophenoxy)methyl)piperidin-1-yl)-5-methoxypyrimidine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 140℃; for 17h; Microwave irradiation;	42%
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 140℃; for 17h; Microwave irradiation;	42%

sodium salt of ethyl cyanoacetate + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → ethyl 5-methoxypyrimidyl-2-cyanoacetate (65364-67-2)

Conditions	Yield
at 90℃; for 1h;	40%

4-Chlorophenylboronic acid (1679-18-1) + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → 2-(4-chloro-phenyl)-5-methoxy-pyrimidine (1078166-55-8)

Conditions	Yield
With potassium carbonate; tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane; water at 100℃; for 0.833333h; Suzuki Coupling;	39.6%

clinafloxacin (105956-97-6) + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → C22H21ClFN5O4

Conditions	Yield
With potassium carbonate In acetonitrile at 80℃; for 25h;	36.3%

2-chloro-5-methoxy-pyrimidine (22536-65-8) + 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)aniline (214360-73-3) → 4-(5-methoxypyrimidin-2-yl)aniline

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,4-dioxane; water at 80℃; for 12h; Inert atmosphere;	36%

bis(tri-n-butyltin) (813-19-4) + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → 2-(tributylstannyl)-5-methoxypyrimidine (727388-71-8)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0) In toluene Inert atmosphere; Reflux;	35.8%
With tetrakis(triphenylphosphine) palladium(0) In toluene for 15h; Inert atmosphere; Reflux;

1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-one hydrochloride (1104442-13-8) + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → 4-(1-(5-methoxypyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one (1104448-30-7)

Conditions	Yield
With hydrogenchloride; potassium carbonate In water; N,N-dimethyl-formamide at 100℃; for 0.166667h; Microwave irradiation; Inert atmosphere;	35%

1-butyn-4-ol (927-74-2) + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → 2-(but-3-ynyloxy)-5-methoxypyrimidine

Conditions	Yield
Stage #1: 3-Butyn-1-ol With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: 2-chloro-5-methoxy-pyrimidine In tetrahydrofuran at 20℃; for 17h; Inert atmosphere;	32%

4-((4-(benzo[d][1,3]oxathiol-6-yl)-2-fluorophenoxy)methyl)piperidine + 2-chloro-5-methoxy-pyrimidine (22536-65-8) → 2-(4-((4-(benzo[d][1,3]oxathiol-6-yl)-2-fluorophenoxy)methyl)piperidin-1-yl)-5-methoxypyrimidine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile Reflux;	31%
With N-ethyl-N,N-diisopropylamine In acetonitrile Reflux;	31%

Upstream product

• 6623-81-0 5-Methoxypyrimidine-2,4(1H,3H)-dione 
• 19646-07-2 2,4-dichloro-5-methoxypyrimidine 

Downstream Products

• 1439936-07-8 1-{4-((5-methoxypyrimidin-2-yl)oxy)-2,6-dimethylphenyl}ethanone 
• 1439936-08-9 2-bromo-1-{4-((5-methoxypyrimidin-2-yl)oxy)-2,6-dimethylphenyl}ethanone 
• 1439936-09-0 4-{4-((5-methoxypyrimidin-2-yl)oxy)-2,6-dimethylphenyl}thiazol-2-amine 
• 1439936-06-7 N-(4-{4-((5-methoxypyrimidin-2-yl)oxy)-2,6-dimethylphenyl}thiazol-2-yl)isonicotinamide 
• 1078166-55-8 2-(4-chloro-phenyl)-5-methoxy-pyrimidine 
• 13418-77-4 5-methoxypyrimidin-2-amine 
• 4983-28-2 2-chloropyrimidine-5-ol 
• 34712-29-3 2‐hydrazinyl‐5‐methoxypyrimidine 
• 59215-39-3 5-methoxy-2-(1-piperazinyl)pyrimidine 

Relevant academic research and scientific papers

Preparation method of 2-chloro-5-methoxypyrimidine

The invention relates to the field of compound preparation methods, and in particular relates to a preparation method of 2-chloro-5-methoxypyrimidine, which is prepared by taking methyl methoxyacetateas a raw material. The product prepared by the preparation method has high purity, the catalyst and the solvent can be recycled, the reaction is mild, the control is easy, and the method is suitablefor industrial production.