5018-38-2

Basic information

• Product Name: 4,6-Dichloro-5-methoxypyrimidine
• Synonyms: 4,6-DICHLORO-5-METHOXYPYRIMIDINE;2,4-dimethoxy-2-methylmercapyrimidine;4,6-Dichlor-5-methoxypyrimidin;4,6-DICHLORO-5-METHOXYPYRIMIDINE 99%;Pyrimidine, 4,6-dichloro-5-methoxy-;2,4-Dichloro-5-MetoxyPyriMidine;5-Methoxy-4,6-dichloropyriMidine;4,6-Dichloro-5-methoxy-1,3-diazine
• CAS NO: 5018-38-2
• Molecular Formula: C₅H₄Cl₂N₂O
• Molecular Weight: 179
• EINECS: 225-699-1
• Product Categories: Pyrimidine series;APIs & Intermediate;Pyrimidine;Pyrimidine Derivertives;Halides;Pyrazines, Pyrimidines & Pyridazines;Heterocycle-Pyrimidine series
• Mol File: 5018-38-2.mol
• Article Data: 7

Chemical Properties

• Melting Point: 50-56℃
• Boiling Point: 257.8 °C at 760 mmHg
• Flash Point: 109.7 °C
• Appearance: /
• Density: 1.446 g/cm³
• Vapor Pressure: 0.023mmHg at 25°C
• Refractive Index: 1.541
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Chloroform (Slightly), Dichloromethane (Slightly)
• PKA: -4.13±0.26(Predicted)
• CAS DataBase Reference: 4,6-Dichloro-5-methoxypyrimidine(CAS DataBase Reference)
• NIST Chemistry Reference: 4,6-Dichloro-5-methoxypyrimidine(5018-38-2)
• EPA Substance Registry System: 4,6-Dichloro-5-methoxypyrimidine(5018-38-2)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 22-41
• Safety Statements: 26-39
• WGK Germany: 3
• Hazardous Substances Data: 5018-38-2(Hazardous Substances Data)

Usage

Chemical Properties

Off-white solid

Uses

4,6-Dichloro-5-methoxypyrimidine is an important raw material and intermediate used in organic synthesis, pharmaceuticals, agrochemicals and dyestuff.

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

Synthetic route

4,6-Dihydroxy-5-methoxypyrimidine (5193-84-0) → 4,6-dichloro-5-methoxypyrimidine (5018-38-2)

Conditions	Yield
With triethylamine; trichlorophosphate In toluene at 100 - 105℃; for 1.5h; Reflux;	86%
With N,N-diethylaniline; trichlorophosphate In heptane-ethyl acetate	75.6%
Stage #1: 4,6-Dihydroxy-5-methoxypyrimidine With trichlorophosphate for 1h; Heating / reflux; Stage #2: With N,N-diethylaniline at 20℃; Heating / reflux;	40%

ethanolamine (141-43-5) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 2-((6-chloro-5-methoxypyrimidin-4-yl)amino)ethanol (1309377-77-2)

Conditions	Yield
With potassium carbonate In 1,4-dioxane at 125℃; Inert atmosphere;	100%
With potassium carbonate In 1,4-dioxane at 140℃; for 1h; Microwave irradiation;
With potassium carbonate In 1,4-dioxane at 125℃; for 8h;	10.5 g

4-amino-3-nitrophenylboronic acid pinacol ester (833486-94-5) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 4-(6-chloro-5-methoxypyrimidin-4-yl)-2-nitroaniline

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane; water at 80℃; for 3h; Suzuki Coupling;	100%

isopropyl 4-hydroxypiperidine-1-carboxylate (832715-51-2) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 4-(6-chloro-5-methoxy-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (897732-25-1)

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at 5 - 10℃; for 2h; Inert atmosphere;	98.6%
With potassium tert-butylate In tetrahydrofuran at 0℃; for 0.75h;	85%
Stage #1: isopropyl 4-hydroxypiperidine-1-carboxylate With potassium tert-butylate In tetrahydrofuran at 20℃; for 0.5h; Stage #2: 4,6-dichloro-5-methoxypyrimidine In tetrahydrofuran at 20℃; for 8h;	65%

(S)-1-(4-Fluoro-phenyl)-ethylamine (66399-30-2) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → (S)-6-chloro-N-(1-(4-fluorophenyl)ethyl)-5-methoxypyrimidin-4-amine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 50℃; for 24h;	98%

1-(tert-butoxycarbonyl)-4-aminopiperidine (87120-72-7) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → tert-butyl 4-(6-chloro-5-methoxypyrimidin-4-ylamino)piperidine-1-carboxylate (1079053-99-8)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 20℃; for 16h;	96%

t-butyl 4-hydroxy piperidine-1-carboxylate (109384-19-2) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 4-(6-Chloro-5-methoxy-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (897732-98-8)

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at 0℃; for 1h;	94.8%

4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 6-amino-4-chloro-5-methoxypyrimidine (5018-41-7)

Conditions	Yield
With ammonium hydroxide In water; isopropyl alcohol at 70℃; for 48h; Autoclave;	94%
With ammonia In water; butan-1-ol at 85℃; for 8h; Sealed tube;	90%
With ammonium hydroxide In butan-1-ol at 85℃; for 8h; Sealed tube;	90%

4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 4-chloro-5,6-dimethoxypyrimidine (5193-88-4)

Conditions	Yield
With sodium methylate In methanol at 0 - 5℃; for 1h;	93%
With sodium methylate In methanol

4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 4,6-dichloropyrimidin-5-ol (425394-89-4)

Conditions	Yield
With aluminum (III) chloride In dichloromethane at 0 - 50℃; for 6h;	91.11%
Stage #1: 4,6-dichloro-5-methoxypyrimidine With aluminum (III) chloride In 1,2-dichloro-ethane at 0 - 50℃; for 6h; Stage #2: With hydrogenchloride; water In methanol; 1,2-dichloro-ethane at 0 - 20℃; for 0.166667h;	91.11%
With aluminum (III) chloride In 1,2-dichloro-ethane at 0 - 50℃; for 6h;

2-methyl-3-pyridinol (1121-25-1) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 4-chloro-5-methoxy-6-[(2-methylpyridin-3-yl)oxy]pyrimidine (1417392-51-8)

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran; N,N-dimethyl-formamide at 70℃; for 1.5h; Inert atmosphere;	87%

4-piperidinemethanol (6457-49-4) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → C11H16ClN3O2 (1422049-36-2)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 20℃;	86%

sodium 4-aminobenzenesulfonylacetamide (127-56-0) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 4-(p-aminobenzenesulfonamido)-5-methoxy-6-chloropyrimidine (5018-23-5)

Conditions	Yield
In N,N-dimethyl-formamide at 88 - 90℃; for 3h;	85.3%

N-(3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine (477600-70-7) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-6-chloro-5-methoxy-N-methylpyrimidin-4-amine

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 70℃; Inert atmosphere;	85%

4,6-dichloro-5-methoxypyrimidine (5018-38-2) + sodium sulfonamide derivative → 4-(p-aminobenzenesulfonamido)-5-methoxy-6-chloropyrimidine (5018-23-5)

Conditions	Yield
In N,N-dimethyl-formamide	85%

2-[2-fluoro-4-[[2-(trifluoromethyl)-4-pyridyl]oxy]phenyl]ethanamine hydrochloride (1448545-46-7) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 6-chloro-N-[2-[2-fluoro-4-[[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]ethyl]-5-methoxy-pyrimidin-4-amine (1448663-73-7)

Conditions	Yield
Stage #1: 2-[2-fluoro-4-[[2-(trifluoromethyl)-4-pyridyl]oxy]phenyl]ethanamine hydrochloride With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 20℃; for 0.0833333h; Stage #2: 4,6-dichloro-5-methoxypyrimidine In 1-methyl-pyrrolidin-2-one at 80℃;	78%

2-[2-fluoro-4-[[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]ethanamine hydrochloride + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 6-chloro-N-[2-[2-fluoro-4-[[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]ethyl]-5-methoxy-pyrimidin-4-amine (1448663-73-7)

Conditions	Yield
Stage #1: 2-[2-fluoro-4-[[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]ethanamine hydrochloride With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 20℃; for 0.0833333h; Stage #2: 4,6-dichloro-5-methoxypyrimidine In 1-methyl-pyrrolidin-2-one at 80℃;	78%
With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 80℃;	78%

sodium salt of sulfanilamide (10103-15-8) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 4-(p-aminobenzenesulfonamido)-5-methoxy-6-chloropyrimidine (5018-23-5)

Conditions	Yield
Stage #1: sodium salt of sulfanilamide; 4,6-dichloro-5-methoxypyrimidine With 1-butyl-3-methylimidazolium chloride at 60 - 92℃; for 1.5h; pH=8 - 9; Stage #2: With hydrogenchloride In water; N,N-dimethyl-formamide pH=7 - 7.2;	77.5%

tert-butyl (3S)-3-aminopiperidine-1-carboxylate (625471-18-3) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 3-(S)-(6-chloro-5-methoxypyrimidin-4-ylamino)piperidine-1-carboxylic acid tert-butyl ester (886584-07-2)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol at 80℃; for 15h;	74%

7-(piperidin-4-yl)-1,2,3,4-tetrahydro-1,8-naphthyridine (315240-28-9) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 6-[4-(1,2,3,4-tetrahydro-1,8-naphthyridin-7-yl)-1-piperidinyl]-5-methoxy-4-chloro-pyrimidine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In ISOPROPYLAMIDE at 130℃; for 2h;	68%

sulfanilamide (63-74-1) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 4-(p-aminobenzenesulfonamido)-5-methoxy-6-chloropyrimidine (5018-23-5)

Conditions	Yield
Stage #1: sulfanilamide With sodium hydroxide at 70℃; for 1h; Stage #2: 4,6-dichloro-5-methoxypyrimidine With N,N-dimethyl-formamide at 95℃; for 3h;	64%

sodium methylate (124-41-4) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 4-chloro-5,6-dimethoxypyrimidine (5193-88-4)

Conditions	Yield
In methanol at 0 - 20℃; for 19h;	57%

methanol (67-56-1) + sodium methylate (124-41-4) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 4-chloro-5,6-dimethoxypyrimidine (5193-88-4)

Conditions	Yield
at 0 - 20℃; for 19h; Inert atmosphere;	57%

4-cyano-2-fluoroaniline (63069-50-1) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 4-((6-chloro-5-methoxypyrimidin-4-yl)amino)-3-fluorobenzonitrile

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 65℃;	55%
With potassium carbonate In N,N-dimethyl-formamide at 65℃;	55%

(4-(3-phenylpropyl)piperidin-4-yl)methanol hydrochloride + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → (1-(6-chloro-5-methoxypyrimidin-4-yl)-4-(3-phenylpropyl)piperidin-4-yl)methanol

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 120℃; for 21h; Sealed tube;	51%

1-(2-fluorophenyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1402240-89-4) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → C14H10ClFN4O

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate In 1,4-dioxane; water at 90℃; for 16h;	40%

1-[4-[[4-(trifluoromethyl)-2-pyridyl]oxy]phenoxy]propan-2-amine hydrochloride + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 6-chloro-5-methoxy-N-[1-methyl-2-[4-[[4-(trifluoromethyl)-2-pyridyl]oxy]phenoxy]ethyl]pyrimidin-4-amine

Conditions	Yield
Stage #1: 1-[4-[[4-(trifluoromethyl)-2-pyridyl]oxy]phenoxy]propan-2-amine hydrochloride With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 20℃; for 0.0833333h; Stage #2: 4,6-dichloro-5-methoxypyrimidine In 1-methyl-pyrrolidin-2-one at 80℃;	37%

2-tri-n-butylstannylpyridine (17997-47-6) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 4-chloro-5-methoxy-6-(pyridin-2-yl)pyrimidine

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0) In toluene for 5h; Inert atmosphere; Reflux;	34%

tyramine hydrochloride (60-19-5) + 4,6-dichloro-5-methoxypyrimidine (5018-38-2) → 6-chloro-N-[2-[4-(6-chloro-5-methoxypyrimidin-4-yl)oxyphenyl]ethyl]-5-methoxypyrimidin-4-amine (1449201-35-7)

Conditions	Yield
Stage #1: tyramine hydrochloride; 4,6-dichloro-5-methoxypyrimidine With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 16h; Stage #2: With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #3: 4,6-dichloro-5-methoxypyrimidine In N,N-dimethyl-formamide at 20℃; for 48h;	31%
With sodium hydride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 64h;	31%

Upstream product

• 5193-84-0 4,6-Dihydroxy-5-methoxypyrimidine 

Downstream Products

• 886584-07-2 3-(S)-(6-chloro-5-methoxypyrimidin-4-ylamino)piperidine-1-carboxylic acid tert-butyl ester 
• 1309377-80-7 4-(4-chloro-6,7-dihydro-8H-pyrimido[5,4-b][1,4]oxazin-8-yl)-3-fluorobenzonitrile 
• 1309377-53-4 C₂₅H₂₈FN₅O₅ 
• 5018-41-7 6-chloro-5-methoxypyrimidine-4-amine 
• 114969-73-2 5-Methoxy-6-phenyl-pyrimidine-4-carbonitrile 
• 1264925-89-4 C₁₉H₂₁N₅OS 
• 1264926-73-9 C₂₀H₁₈N₄O₂ 
• 1264926-91-1 N₆-(5-methoxy-6-p-tolylpyrimidin-4-yl)benzo[d]isoxazole-3,6-diamine 
• 1264926-02-4 N-[5-methoxy-6-(4-methylphenyl)-4-pyrimidinyl]-7-isoquinolinamine 

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