289042-11-1

Basic information

• Product Name: Methyl 4-(4-fluorophenyl)-6-isopropyl-2-[(N-methyl-N-methylsulfonyl)amino]pyrimidine-5-carboxylate
• Synonyms: 4-(4-FLUOROPHENYL)-6-ISOPROPYL-2-[(METHANESULFONYL)METHYLAMINO]PYRIMIDINE-5-CARBOXYLIC ACID METHYL ESTER;METHYL 4-(4-FLUOROPHENYL)-6-ISOPROPYL-2-[(N-METHYL-N-METHANESULFONYL)-AMINO]-PYRIMIDINE-5-CARBOXYLATE;methyl 4-(4-fluorophenyl)-6-isopropyl-2-[(n-methyl-n-methylsulfonyl)amino]pyrimidine-5-carboxylate;R1-METHYL-4-(FLUOROMETHYL)-6-ISOPROPYL-2-(N-METHYLSULFONYLAMINO)PYRIMIDINO-5-CARBOXYLATE;Rosuvastatin intermediate R-1-1;ZD-1 ;4-(4-Fluorophenyl)-6-Isopropyl-2-(N-Methyl-N-Methylsulfonylamino)Pyrimidine-5-Carboxylate;( Carboxylate) 4-(4-Fluorophenyl)-6-Isopropyl-2-(N-Methyl-N-Methylsulfonyl amino)Pyrimidine-5-Carboxylate
• CAS NO: 289042-11-1
• Molecular Formula: C₁₇H₂₀FN₃O₄S
• Molecular Weight: 381.42
• EINECS: 1308068-626-2
• Product Categories: INTERMEDIATESOFROSUVASTATINCALCIUM;Rosuvastatin Calcium and its intermediates;Rosuvastatin intermediates;Amines;Aromatics;Bases & Related Reagents;Heterocycles;Nucleotides;Sulfur & Selenium Compounds
• Mol File: 289042-11-1.mol
• Article Data: 11

Chemical Properties

• Boiling Point: 551.956 °C at 760 mmHg
• Flash Point: 287.613 °C
• Appearance: White or off-white powder
• Density: 1.305 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.557
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), Ethyl Acetate (Slightly)
• PKA: -1.85±0.10(Predicted)
• CAS DataBase Reference: Methyl 4-(4-fluorophenyl)-6-isopropyl-2-[(N-methyl-N-methylsulfonyl)amino]pyrimidine-5-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: Methyl 4-(4-fluorophenyl)-6-isopropyl-2-[(N-methyl-N-methylsulfonyl)amino]pyrimidine-5-carboxylate(289042-11-1)
• EPA Substance Registry System: Methyl 4-(4-fluorophenyl)-6-isopropyl-2-[(N-methyl-N-methylsulfonyl)amino]pyrimidine-5-carboxylate(289042-11-1)

Safety Data

• Hazardous Substances Data: 289042-11-1(Hazardous Substances Data)

Usage

Uses

An intermediate of Rosuvastatin (R700500).

InChI:InChI=1/C17H20FN3O4S/c1-10(2)14-13(16(22)25-4)15(11-6-8-12(18)9-7-11)20-17(19-14)21(3)26(5,23)24/h6-10H,1-5H3

Synthetic route

4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-3,4-dihydropyrimidine-2(1H)-one + N-methylmethane sulphonamide (1184-85-6) → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
Stage #1: methyl 4-(4-fluorophenyl)-2-hydroxy-6-isopropylpyrimidine-5-carboxylate With potassium carbonate; p-toluenesulfonyl chloride In acetic acid butyl ester at 45℃; for 0.5h; Stage #2: N-methylmethane sulphonamide With potassium carbonate In acetic acid butyl ester at 125℃; for 3h;	94%

N-methylmethane sulphonamide (1184-85-6) + 2-chloro-4-(4-fluoro-phenyl)-6-isopropyl-pyrimidine-5-carboxylic acid methyl ester (488798-38-5) → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
Stage #1: N-methylmethane sulphonamide With sodium hydride In acetonitrile; mineral oil for 0.0833333h; Stage #2: 2-chloro-4-(4-fluoro-phenyl)-6-isopropyl-pyrimidine-5-carboxylic acid methyl ester In acetonitrile; mineral oil for 7h; Reagent/catalyst; Solvent; Reflux;	93.2%

4-(4-fluorophenyl)-6-isopropyl-2-(methylsulfonyl)pyrimidine-5-carboxylic acid methyl ester (799842-06-1) + sodium salt of N-methyl-N-methylsulfonylamine (41881-75-8) → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
In N,N-dimethyl-formamide at 30℃; for 1h;	92.42%

4-(4-fluorophenyl)-6-isopropyl-2-(methylsulfonyl)pyrimidine-5-carboxylic acid methyl ester (799842-06-1) + N-methylmethane sulphonamide (1184-85-6) → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
With potassium carbonate In acetonitrile at 25 - 85℃; for 2.5 - 3h; Product distribution / selectivity; Heating / reflux;	87.93%
With potassium carbonate In acetic acid butyl ester at 90℃; for 3h; Product distribution / selectivity;

methyl 4-(4-fluorophenyl)-6-isopropyl-2-(methylamino)pyrimidine-5-carboxylate (160009-36-9) + methanesulfonyl chloride (124-63-0) → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
Stage #1: methyl 4-(4-fluorophenyl)-6-isopropyl-2-(methylamino)pyrimidine-5-carboxylate With sodium tert-pentoxide In 1,2-dimethoxyethane at 20℃; for 1h; Inert atmosphere; Stage #2: methanesulfonyl chloride In 1,2-dimethoxyethane at -10℃; for 1h;	78%
Stage #1: methyl 4-(4-fluorophenyl)-6-isopropyl-2-(methylamino)pyrimidine-5-carboxylate With sodium tert-pentoxide In 1,2-dimethoxyethane at 20℃; for 0.5h; Stage #2: methanesulfonyl chloride In 1,2-dimethoxyethane at -10℃; for 0.5h;	76%
With n-butyllithium In tetrahydrofuran; hexane at -75 - -70℃;	63%
Stage #1: methyl 4-(4-fluorophenyl)-6-isopropyl-2-(methylamino)pyrimidine-5-carboxylate With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.25h; Stage #2: methanesulfonyl chloride In N,N-dimethyl-formamide for 1h; Product distribution / selectivity;

methyl 2-[1-amino-1-(4-fluorophenyl)methylene]-4-methyl-3-oxopentanoate + sodium tert-pentoxide (14593-46-5) + cyanogen chloride (506-77-4) → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
In water	74.1%

methyl 2-[1-amino-1-(4-fluorophenyl)methylene]-4-methyl-3-oxopentanoate + N-methylmethane sulphonamide (1184-85-6) + cyanogen chloride (506-77-4) → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
With sodium t-butanolate In methanol; water; tert-butyl alcohol	56.3%
In N,N-dimethyl acetamide; water; acetone	29% [concentration (GC)
In N,N-dimethyl acetamide; water; acetone	30.2% [concentration (GC)
In water; acetone

N-cyano-N-methylmethanesulphonamide (317806-76-1) + methyl 2-[1-amino-1-(4-fluorophenyl)methylene]-4-methyl-3-oxopentanoate + N-methylmethane sulphonamide (1184-85-6) → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
With sodium t-butanolate In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; tert-butyl alcohol	52.1%

N-cyano-N-methylmethanesulphonamide (317806-76-1) + methyl 2-[1-amino-1-(4-fluorophenyl)methylene]-4-methyl-3-oxopentanoate → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
In N,N-dimethyl acetamide; water	27%
In N,N-dimethyl acetamide; water
titanium tetrachloride In water; toluene	13.5% [concentration (HPLC)

methyl 2-[1-amino-1-(4-fluorophenyl)methylene]-4-methyl-3-oxopentanoate + N-methylmethane sulphonamide (1184-85-6) + N,N-dimethyl acetamide (127-19-5) + cyanogen chloride (506-77-4) → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
In water	22%

methyl 3-amino-2-[1-(4-fluorophenyl)methanoyl]-4-methylpent-2-enoate + N-methylmethane sulphonamide (1184-85-6) + cyanogen chloride (506-77-4) → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
With sodium t-butanolate In tert-butyl alcohol	13.6%

methyl 3-amino-2-[1-(4-fluorophenyl)methanoyl]-4-methylpent-2-enoate + N-cyano-N-methylmethanesulphonamide (317806-76-1) + N-methylmethane sulphonamide (1184-85-6) → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
With sodium t-butanolate In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; tert-butyl alcohol	9.8%

methyl 4-(4-fluorophenyl)-6-isopropyl-2-methylsulfinylpyrimidine-5-carboxylate (904743-95-9) + N-methylmethane sulphonamide (1184-85-6) → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
With potassium carbonate In acetic acid butyl ester at 90℃; Product distribution / selectivity;

methyl 2-amino-4-(4-fluorophenyl)-6-isopropyl-pyrimidine-5-carboxylate (160009-37-0) + sodium tert-pentoxide (14593-46-5) + methanesulfonyl chloride (124-63-0) → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
With sodium chloride; dimethyl sulfate In 1,2-dimethoxyethane; water

N-cyano-N-methylmethanesulphonamide (317806-76-1) + methyl 2-[1-amino-1-(4-fluorophenyl)methylene]-4-methyl-3-oxopentanoate + sodium tert-pentoxide (14593-46-5) → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
In N,N-dimethyl acetamide; ISOPROPYLAMIDE; water

methyl 2-amino-4-(4-fluorophenyl)-6-isopropyl-pyrimidine-5-carboxylate (160009-37-0) + methanesulfonyl chloride (124-63-0) → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
Stage #1: methyl 2-amino-4-(4-fluorophenyl)-6-isopropyl-pyrimidine-5-carboxylate With sodium tert-pentoxide In 1,2-dimethoxyethane at 25℃; for 0.5h; Stage #2: methanesulfonyl chloride In 1,2-dimethoxyethane at -10 - -5℃; for 0.333333h; Stage #3: With sodium tert-pentoxide; dimethyl sulfate more than 3 stages;

4-fluorobenzaldehyde (459-57-4) → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: copper(l) chloride; sulfuric acid / methanol / 24 h / 80 °C / Inert atmosphere 2.1: copper dichloride; potassium carbonate; tert.-butylhydroperoxide / dichloromethane / 7 h / 40 °C 3.1: trichlorophosphate; N,N-dimethyl-aniline / 2.5 h / 80 °C / Inert atmosphere 4.1: sodium hydride / mineral oil; acetonitrile / 0.08 h 4.2: 7 h / Reflux View Scheme
Multi-step reaction with 4 steps 1.1: copper(l) chloride; sulfuric acid / methanol / 24 h / 80 °C / Inert atmosphere 2.1: copper dichloride; potassium carbonate; tert.-butylhydroperoxide / dichloromethane / 7 h / 40 °C 3.1: trichlorophosphate; N,N-dimethyl-aniline / 2.5 h / 80 °C / Inert atmosphere 4.1: sodium hydride / mineral oil; acetonitrile / 0.08 h 4.2: 7 h / Reflux View Scheme
Multi-step reaction with 3 steps 1.1: copper(l) chloride; sulfuric acid / methanol / 9 h / 78 °C 2.1: dipotassium peroxodisulfate / water / Reflux 3.1: potassium carbonate; p-toluenesulfonyl chloride / acetic acid butyl ester / 0.5 h / 45 °C 3.2: 3 h / 125 °C View Scheme

Methyl 4-methyl-3-oxopentanoate (42558-54-3) → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: copper(l) chloride; sulfuric acid / methanol / 24 h / 80 °C / Inert atmosphere 2.1: copper dichloride; potassium carbonate; tert.-butylhydroperoxide / dichloromethane / 7 h / 40 °C 3.1: trichlorophosphate; N,N-dimethyl-aniline / 2.5 h / 80 °C / Inert atmosphere 4.1: sodium hydride / mineral oil; acetonitrile / 0.08 h 4.2: 7 h / Reflux View Scheme
Multi-step reaction with 4 steps 1.1: copper(l) chloride; sulfuric acid / methanol / 24 h / 80 °C / Inert atmosphere 2.1: copper dichloride; potassium carbonate; tert.-butylhydroperoxide / dichloromethane / 7 h / 40 °C 3.1: trichlorophosphate; N,N-dimethyl-aniline / 2.5 h / 80 °C / Inert atmosphere 4.1: sodium hydride / mineral oil; acetonitrile / 0.08 h 4.2: 7 h / Reflux View Scheme
Multi-step reaction with 3 steps 1.1: copper(l) chloride; sulfuric acid / methanol / 9 h / 78 °C 2.1: dipotassium peroxodisulfate / water / Reflux 3.1: potassium carbonate; p-toluenesulfonyl chloride / acetic acid butyl ester / 0.5 h / 45 °C 3.2: 3 h / 125 °C View Scheme

methyl 4-(4-fluorophenyl)-6-isopropyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: copper dichloride; potassium carbonate; tert.-butylhydroperoxide / dichloromethane / 7 h / 40 °C 2.1: trichlorophosphate; N,N-dimethyl-aniline / 2.5 h / 80 °C / Inert atmosphere 3.1: sodium hydride / mineral oil; acetonitrile / 0.08 h 3.2: 7 h / Reflux View Scheme
Multi-step reaction with 3 steps 1.1: copper dichloride; potassium carbonate; tert.-butylhydroperoxide / dichloromethane / 7 h / 40 °C 2.1: trichlorophosphate; N,N-dimethyl-aniline / 2.5 h / 80 °C / Inert atmosphere 3.1: sodium hydride / mineral oil; acetonitrile / 0.08 h 3.2: 7 h / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: dipotassium peroxodisulfate / water / Reflux 2.1: potassium carbonate; p-toluenesulfonyl chloride / acetic acid butyl ester / 0.5 h / 45 °C 2.2: 3 h / 125 °C View Scheme

4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-3,4-dihydropyrimidine-2(1H)-one → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: trichlorophosphate; N,N-dimethyl-aniline / 2.5 h / 80 °C / Inert atmosphere 2.1: sodium hydride / mineral oil; acetonitrile / 0.08 h 2.2: 7 h / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: trichlorophosphate; N,N-dimethyl-aniline / 2.5 h / 80 °C / Inert atmosphere 2.1: sodium hydride / mineral oil; acetonitrile / 0.08 h 2.2: 7 h / Reflux View Scheme

N-methylmethane sulphonamide (1184-85-6) + 2-chloro-4-(4-fluoro-phenyl)-6-isopropyl-pyrimidine-5-carboxylic acid methyl ester (488798-38-5) → methyl 4-(4-fluorophenyl)-6-isopropyl-2-(methylamino)pyrimidine-5-carboxylate (160009-36-9) + methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1) + 4-(4-fluorophenyl)-6-isopropyl-2-(methanesulfonyl(methyl)amino)pyrimidine-5-carboxylic acid (1263475-93-9)

Conditions	Yield
Stage #1: N-methylmethane sulphonamide With sodium hydride In acetonitrile; mineral oil for 0.0833333h; Stage #2: 2-chloro-4-(4-fluoro-phenyl)-6-isopropyl-pyrimidine-5-carboxylic acid methyl ester In acetonitrile; mineral oil for 7h; Reflux;

methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Stage #1: methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate With diisobutylaluminium hydride In hexane; toluene at -10℃; for 1h; Stage #2: With hydrogenchloride In methanol; hexane; water; toluene at -10 - 40℃; for 0.333333h;	100%
Stage #1: methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate With sodium tetrahydroborate; boron trifluoride diethyl etherate In tetrahydrofuran at 0 - 60℃; for 20h; Stage #2: With hydrogenchloride In tetrahydrofuran; water for 1.5h; Temperature; Reagent/catalyst; Solvent;	96.7%
Stage #1: methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate With diisobutylaluminium hydride In toluene at -15 - -5℃; for 2 - 2.5h; Stage #2: With hydrogenchloride; water In toluene at -10 - 40℃; for 1 - 1.33333h; Stage #3: With sodium hydrogencarbonate In water; ethyl acetate Product distribution / selectivity;	93%

methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1) → 4-(4-fluorophenyl)-6-isopropyl-2-(methanesulfonyl(methyl)amino)pyrimidine-5-carboxylic acid (1263475-93-9)

Conditions	Yield
With sodium hydroxide In ethanol at 82℃; for 0.5h;	95.8%
With lithium hydroxide In tetrahydrofuran; water at 60 - 70℃;	90.5%
With water; lithium hydroxide In tetrahydrofuran at 60 - 70℃;	90.5%

methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate (289042-11-1) + Ethyl diphenylphosphinite (719-80-2) → N-(5-((diphenylphosphoryl)methyl)-4-(4-fluorophenyl)- 6-isopropylpyrimidin-2-yl)-N-methylmethansulfonamide (289042-10-0)

Conditions	Yield
Stage #1: methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate With diisobutylaluminium hydride In toluene at -10 - 0℃; for 2.5h; Stage #2: With hydrogenchloride In methanol; water; acetonitrile at 0 - 40℃; for 2.83333h; Stage #3: Ethyl diphenylphosphinite With phosphorus tribromide more than 3 stages;

Upstream product

• 14593-46-5 sodium tert-pentoxide 
• 506-77-4 cyanogen chloride 
• 317806-76-1 N-cyano-N-methylmethanesulphonamide 
• 1184-85-6 N-methylmethane sulphonamide 
• 488798-38-5 2-chloro-4-(4-fluoro-phenyl)-6-isopropyl-pyrimidine-5-carboxylic acid methyl ester 
• 42558-54-3 Methyl 4-methyl-3-oxopentanoate 
• 459-57-4 4-fluorobenzaldehyde 
• 160009-37-0 methyl 2-amino-4-(4-fluorophenyl)-6-isopropyl-pyrimidine-5-carboxylate 
• 124-63-0 methanesulfonyl chloride 
• 799842-06-1 4-(4-fluorophenyl)-6-isopropyl-2-(methylsulfonyl)pyrimidine-5-carboxylic acid methyl ester 
• 41881-75-8 sodium salt of N-methyl-N-methylsulfonylamine 
• 127-19-5 N,N-dimethyl acetamide 
• 160009-36-9 methyl 4-(4-fluorophenyl)-6-isopropyl-2-(methylamino)pyrimidine-5-carboxylate 
• 904743-95-9 methyl 4-(4-fluorophenyl)-6-isopropyl-2-methylsulfinylpyrimidine-5-carboxylate 

Downstream Products

• 289042-10-0 N-(5-((diphenylphosphoryl)methyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide 
• 1263475-93-9 4-(4-fluorophenyl)-6-isopropyl-2-(methanesulfonyl(methyl)amino)pyrimidine-5-carboxylic acid 
• 147118-36-3 N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide 

Relevant articles and documents

Preparation method of rosuvastatin calcium intermediate

The invention provides a preparation method of a rosuvastatin calcium intermediate. The preparation method of the rosuvastatin calcium intermediate, namely, the compound shown as formula I in the description comprises the following steps: (1) a compound 5 shown as formula II in the description is generated from 4-fluorobenzaldehyde, methyl isobutyrylacetate and urea under the action of a catalyst; (2) a compound 6 shown as formula III in the description is generated from the compound 5 under the action of potassium persulfate as an oxidizing agent; (3) a compound 7 shown as formula IV in the description is generated from the compound 6, tosyl chloride and N-methyl methanesulfonamide under the action of a catalyst; (4) the target compound shown as the formula I is generated from the compound 7 under the action of a vitride solution as a reducing agent and crystallized with a crystallization solution, and a purified target compound is obtained. The preparation method of the rosuvastatin calcium intermediate has the advantages of low production cost, mild condition and simple and convenient operation.

Synthesis, characterization and crystal structure of N-(4-(4-Fluorophenyl)-5-(hydroxymethyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide

N-[4-(4-Fluorophenyl)-5-(hydroxymethyl)-6-isopropylpyrimidin-2-yl]-N-methylmethane sulfonamide (I), an important intermediate to synthesize rosuvastatin, an HMG-CoA reductase inhibitor. It was prepared from methyl 4-(4-fluorophenyl)-6-isopropyl-2-(methylamino)pyrimidine-5-carboxylate (1) via mesylation by mesyl chloride and sodium tert-pentoxide, then reduction by DIBAL/HCl. The product was characterized by NMR and LC-MS. The crystal structure of compound I was investigated using X-ray diffraction and SHELXTL-97 software. The result indicated that compound I crystallized in the monoclinic system, space group C2/C with a = 29.683(6), b = 7.6290 (15), c = 18.215(4) ?, V = 3451.1 (16) ?3; Z 8.

PREPARATION OF ALKYL 4-(4-FLUOROPHENYL)-6-ISOPROPYL-2-[METHYL(METHYLSULFONY)AMINO]-PYRIMIDINE-5-CARBOXYLATE AND ITS SUBSEQUENT CONVERSION TO N-[4-(4-FLUOROPHENYL)-5-FORMYL-6-ISOPROPYL PYRIMIDIN-2-YL]-N-METHYLMETHANESULFONAMIDE-A KEY INTERMEDIATE IN THE SYNTHESIS OF ROSUVASTATIN

The present invention discloses a novel process to prepare a compound of formula (IIA). By reacting a compound of formula-[D], wherein R1 is C1 to C6 alkyl, preferably R1 is methyl or ethyl, more preferably R1 is methyl ; and R2 is C1 to C8 n-alkyl or branched alkyl, cycloalkyl, phenyl , benzyl or substituted phenyl group, preferably R2 is methyl ; with N-methyl methanesulfonamide and a base, optionally with a salt of N-methyl methanesulfonamide, in suitable solvent(s) , to give a compound of formula (IIA), followed by converting compound of formula (IIA) to a compound for formula -[B], by a known process and finally converting a compound of formula (B) to a compound of formula (II), by a novel process using calcium hypochlorite / TEMPO as an oxidant.