147118-36-3

Basic information

• Product Name: 4-(4-Fluorophenyl)-6-isopropyl-2-[(N-methyl-n-methylsulfonyl)amino]pyrimidine-5-yl-methanol
• Synonyms: 4-(4-FLUOROPHENYL)-6-ISOPROPYL-2-(N-METHYL-N-METHYLSULFONYLAMINO)PYRIMIDINE-5-METHANOL;4-(4-FLUOROPHENYL)-6-ISOPROPYL-2-[(N-METHYL-N-METHYLSULFONYL)AMINO]PYRIMIDINE-5-YL-METHANOL;4-(4-FLUOROPHENYL)-6-ISOPROPYL-2-(N-METHYL-N-METHYLSULFONYLAMINO)PYRIMIDINE-5-ME;ZD-2 ;4-(4-Fluorophenyl)-6-Isopropyl-2-[(N-Methyl-N-Methylsulfonyl)Amino]Pyrimidin-5-Yl-Methanol;(Methanol) 4-(4-Fluorophenyl)-6-Isopropyl-2-(N-Methyl-N-Methylsulfonylamino)Pyrimidine-5-yl-Methanol;4-(4-Fluorophenyl)-6-isopropyl-2- [(N-methyl-N- methylsulfony)amino]pyrimidine-5-yl-methanol;4-(4-Fluorophenyl)-6-Isopropyl-2-(N-Mehyl-N-Mehylsulfonylamino)Pyrimidine-5-yl-Methanol
• CAS NO: 147118-36-3
• Molecular Formula: C₁₆H₂₀FN₃O₃S
• Molecular Weight: 353.41
• EINECS: 1312995-182-4
• Product Categories: INTERMEDIATESOFROSUVASTATINCALCIUM;Rosuvastatin Calcium and its intermediates;Rosuvastatin intermediates;Heterocycles;Inhibitors;Intermediates;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;Fluorine series;INTERMEDIATES OF ROSUVASTATIN
• Mol File: 147118-36-3.mol
• Article Data: 26

Chemical Properties

• Boiling Point: 538.273 °C at 760 mmHg
• Flash Point: 279.338 °C
• Appearance: White or off-white powder
• Density: 1.317 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.579
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 13.02±0.10(Predicted)
• CAS DataBase Reference: 4-(4-Fluorophenyl)-6-isopropyl-2-[(N-methyl-n-methylsulfonyl)amino]pyrimidine-5-yl-methanol(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(4-Fluorophenyl)-6-isopropyl-2-[(N-methyl-n-methylsulfonyl)amino]pyrimidine-5-yl-methanol(147118-36-3)
• EPA Substance Registry System: 4-(4-Fluorophenyl)-6-isopropyl-2-[(N-methyl-n-methylsulfonyl)amino]pyrimidine-5-yl-methanol(147118-36-3)

Safety Data

• Hazardous Substances Data: 147118-36-3(Hazardous Substances Data)

Usage

Description

4-(4-Fluorophenyl)-6-isopropyl-2-[(N-methyl-n-methylsulfonyl)amino]pyrimidine-5-yl-methanol is a complex organic compound characterized by its unique molecular structure. It is a white solid with specific chemical properties that make it a valuable intermediate in the pharmaceutical industry.

Uses

Used in Pharmaceutical Industry:
4-(4-Fluorophenyl)-6-isopropyl-2-[(N-methyl-n-methylsulfonyl)amino]pyrimidine-5-yl-methanol is used as an intermediate for the synthesis of Rosuvastatin (R700500), a HMG-CoA reductase inhibitor. 4-(4-Fluorophenyl)-6-isopropyl-2-[(N-methyl-n-methylsulfonyl)amino]pyrimidine-5-yl-methanol plays a crucial role in the development of Rosuvastatin, which is a widely prescribed medication for lowering cholesterol levels and reducing the risk of cardiovascular diseases.
As a Rosuvastatin (R700500) intermediate, 4-(4-Fluorophenyl)-6-isopropyl-2-[(N-methyl-n-methylsulfonyl)amino]pyrimidine-5-yl-methanol contributes to the production of a drug that effectively manages high cholesterol and helps prevent heart attacks and strokes in patients at risk.

InChI:InChI=1/C16H20FN3O3S/c1-10(2)14-13(9-21)15(11-5-7-12(17)8-6-11)19-16(18-14)20(3)24(4,22)23/h5-8,10,21H,9H2,1-4H3

Synthetic route

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%

N-[5-(bromomethyl)-4-(4-fluorophenyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (799842-07-2) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
With water In tetrahydrofuran for 6h; Reflux;	100%
With oxygen; eosin y In dimethyl sulfoxide at 40℃; Irradiation;	82%
With water; sodium hydrogencarbonate In acetonitrile for 4h; Reflux;
With water; sodium hydrogencarbonate In acetonitrile for 4h; Reflux;
With sodium hydrogencarbonate In acetonitrile for 4h; Reflux;

N-[4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide (147118-37-4) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
With methanol; sodium tetrahydroborate In tetrahydrofuran at 5 - 25℃; for 2h;	98%
With methanol; sodium tetrahydroborate In tetrahydrofuran at 5 - 10℃;
With methanol; sodium tetrahydroborate In tetrahydrofuran at 0 - 20℃; for 1h;

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

Conditions	Yield
With lithium borohydride; boron trifluoride diethyl etherate In tetrahydrofuran at -5 - 20℃; for 4h; Reagent/catalyst; Temperature;	97.8%
With chloro-trimethyl-silane; potassium borohydride In tetrahydrofuran at 65℃; for 30h; Temperature; Reagent/catalyst; Inert atmosphere;	97%
Stage #1: 4-(4-fluorophenyl)-6-isopropyl-2-(methanesulfonyl(methyl)amino)pyrimidine-5-carboxylic acid With potassium borohydride In tetrahydrofuran for 0.0833333h; Cooling with ice; Stage #2: With aluminum (III) chloride In tetrahydrofuran at 74℃; for 4.08333h; Reagent/catalyst;	97.9%
With sodium tetrahydroborate; boron trifluoride diethyl etherate In tetrahydrofuran at -5 - 30℃; Reagent/catalyst; Temperature;	96.4%
With sodium tetrahydroborate; chloro-trimethyl-silane In tetrahydrofuran for 24h; Reagent/catalyst; Reflux; Inert atmosphere;	92%

methyl 4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methanesulfonyl)amino]pyrimidin-5-carboxylate → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
With sodium tetrahydroborate In methanol for 4h;	88.1%

ethyl 2-(N-methyl-N-methanesulfonylamino)-4-(4-fluorophenyl)-6-isopropyl-pyrimidin-5-carboxylic acid (147118-30-7) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Stage #1: ethyl 2-(N-methyl-N-methanesulfonylamino)-4-(4-fluorophenyl)-6-isopropyl-pyrimidin-5-carboxylic acid With diisobutylaluminium hydride In toluene at -78 - 0℃; Inert atmosphere; Stage #2: With water In toluene	81%
With diisobutylaluminium hydride In toluene at -74℃; for 1h;	277 mg
Multi-step reaction with 2 steps 1: lithium hydroxide monohydrate / water; methanol / 60 - 70 °C 2: lithium borohydride; boron trifluoride diethyl etherate / tetrahydrofuran / 4 h / -5 - 20 °C View Scheme
Multi-step reaction with 2 steps 1: lithium hydroxide monohydrate; water / methanol / 60 - 70 °C 2: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / -5 - 30 °C View Scheme

4-fluorobenzaldehyde (459-57-4) + PhCH2CH2MgHal → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: 86.7 percent / piperidine, AcOH / benzene / Heating 2: 1.) HMPA, 2.) DDQ / 1.) 100 deg C, 22 h, 2.) benzene, 30 min 3: 95.7 percent / m-CPBA / CHCl3 / Ambient temperature 4: 46.9 g / ethanol / 1 h / Ambient temperature 5: 1.) NaH / 1.) DMF, 30 min, 2.) DMF, RT, 2 h 6: 277 mg / DIBAL-H / toluene / 1 h / -74 °C View Scheme

(E)-2-<(4-fluorophenyl)methylene>-4-methyl-3-oxopentanoic acid ethyl ester (122930-45-4) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 1.) HMPA, 2.) DDQ / 1.) 100 deg C, 22 h, 2.) benzene, 30 min 2: 95.7 percent / m-CPBA / CHCl3 / Ambient temperature 3: 46.9 g / ethanol / 1 h / Ambient temperature 4: 1.) NaH / 1.) DMF, 30 min, 2.) DMF, RT, 2 h 5: 277 mg / DIBAL-H / toluene / 1 h / -74 °C View Scheme

ethyl 4-methyl-3-oxo-pentanoate (7152-15-0) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: 86.7 percent / piperidine, AcOH / benzene / Heating 2: 1.) HMPA, 2.) DDQ / 1.) 100 deg C, 22 h, 2.) benzene, 30 min 3: 95.7 percent / m-CPBA / CHCl3 / Ambient temperature 4: 46.9 g / ethanol / 1 h / Ambient temperature 5: 1.) NaH / 1.) DMF, 30 min, 2.) DMF, RT, 2 h 6: 277 mg / DIBAL-H / toluene / 1 h / -74 °C View Scheme

5-ethoxycarbonyl-6-(4'-fluorophenyl)-4-isopropyl-2-(methylamino)pyrimidine (147118-32-9) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) NaH / 1.) DMF, 30 min, 2.) DMF, RT, 2 h 2: 277 mg / DIBAL-H / toluene / 1 h / -74 °C View Scheme

ethyl 4-(4-fluorophenyl)-2-(methylsulfanyl)-6-(propan-2-yl)-pyrimidine-5-carboxylate (147118-27-2) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 95.7 percent / m-CPBA / CHCl3 / Ambient temperature 2: 46.9 g / ethanol / 1 h / Ambient temperature 3: 1.) NaH / 1.) DMF, 30 min, 2.) DMF, RT, 2 h 4: 277 mg / DIBAL-H / toluene / 1 h / -74 °C View Scheme

ethyl 4-(4-fluorophenyl)-6-isopropyl-2-(methylsulfonyl)pyrimidine-5-carboxylate (147118-28-3) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 46.9 g / ethanol / 1 h / Ambient temperature 2: 1.) NaH / 1.) DMF, 30 min, 2.) DMF, RT, 2 h 3: 277 mg / DIBAL-H / toluene / 1 h / -74 °C View Scheme

N-(4-(4-fluorophenyl)-6-isopropyl-5-methylpyrimidin-2-yl)-N-methylmethanesulfonamide (953776-62-0) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-Bromosuccinimide / acetonitrile / 0.5 h / UV-irradiation; Inert atmosphere; Sealed flow reactor 2: sodium hydrogencarbonate; water / acetonitrile / 4 h / Reflux View Scheme
Stage #1: N-(4-(4-fluorophenyl)-6-isopropyl-5-methylpyrimidin-2-yl)-N-methylmethanesulfonamide With N-Bromosuccinimide In acetonitrile at 20℃; for 4h; UV-irradiation; Stage #2: With sodium hydrogencarbonate In acetonitrile for 4h; Reflux; Stage #3: With water In acetonitrile at 20℃;
Multi-step reaction with 2 steps 1: N-Bromosuccinimide / acetonitrile / 16 h / 20 °C / Inert atmosphere; UV-irradiation 2: water / tetrahydrofuran / 6 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: N-Bromosuccinimide / acetonitrile / 68 h / 20 °C / UV-irradiation 2: sodium hydrogencarbonate / acetonitrile / 4 h / Reflux View Scheme

1-(4-Fluorophenyl)-3-isopropylpropan-1,3-dione (114433-94-2) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: potassium carbonate / acetone / 24 h / 20 °C 2: caesium carbonate / 2-methyltetrahydrofuran / 10 h / 40 °C 3: triethylamine / dichloromethane / 8 h / -5 °C / Inert atmosphere 4: N-Bromosuccinimide / acetonitrile / 0.5 h / UV-irradiation; Inert atmosphere; Sealed flow reactor 5: sodium hydrogencarbonate; water / acetonitrile / 4 h / Reflux View Scheme
Multi-step reaction with 5 steps 1: potassium carbonate / acetone / 48 h / 20 °C / Inert atmosphere 2: potassium tert-butylate / tert-butyl alcohol / 24 h / 70 °C 3: triethylamine / dichloromethane / 8 h / -5 °C / Inert atmosphere 4: N-Bromosuccinimide / acetonitrile / 16 h / 20 °C / Inert atmosphere; UV-irradiation 5: water / tetrahydrofuran / 6 h / Reflux View Scheme
Multi-step reaction with 5 steps 1: potassium carbonate / acetone / 48 h / 20 °C / Inert atmosphere 2: caesium carbonate / 2-methyltetrahydrofuran / 24 h / 70 °C 3: triethylamine / dichloromethane / 8 h / -5 °C / Inert atmosphere 4: N-Bromosuccinimide / acetonitrile / 16 h / 20 °C / Inert atmosphere; UV-irradiation 5: water / tetrahydrofuran / 6 h / Reflux View Scheme
Multi-step reaction with 5 steps 1.1: potassium carbonate / acetone / 24 h / 20 °C 2.1: tetrahydrofuran / 0.17 h / 20 °C 2.2: 8 h / 40 °C 3.1: triethylamine / dichloromethane / 26 h / 0 - 20 °C 4.1: N-Bromosuccinimide / acetonitrile / 68 h / 20 °C / UV-irradiation 5.1: sodium hydrogencarbonate / acetonitrile / 4 h / Reflux View Scheme

4-(4-fluorophenyl)-6-isopropyl-N,5-dimethylpyrimidin-2-amine (1207460-34-1) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 8 h / -5 °C / Inert atmosphere 2: N-Bromosuccinimide / acetonitrile / 0.5 h / UV-irradiation; Inert atmosphere; Sealed flow reactor 3: sodium hydrogencarbonate; water / acetonitrile / 4 h / Reflux View Scheme
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 8 h / -5 °C / Inert atmosphere 2: N-Bromosuccinimide / acetonitrile / 16 h / 20 °C / Inert atmosphere; UV-irradiation 3: water / tetrahydrofuran / 6 h / Reflux View Scheme
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 26 h / 0 - 20 °C 2: N-Bromosuccinimide / acetonitrile / 68 h / 20 °C / UV-irradiation 3: sodium hydrogencarbonate / acetonitrile / 4 h / Reflux View Scheme

1-(4-fluorophenyl)-2-methyl-3-isopropylpropan-1,3-dione (1354455-77-8) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: caesium carbonate / 2-methyltetrahydrofuran / 10 h / 40 °C 2: triethylamine / dichloromethane / 8 h / -5 °C / Inert atmosphere 3: N-Bromosuccinimide / acetonitrile / 0.5 h / UV-irradiation; Inert atmosphere; Sealed flow reactor 4: sodium hydrogencarbonate; water / acetonitrile / 4 h / Reflux View Scheme
Multi-step reaction with 4 steps 1: potassium tert-butylate / tert-butyl alcohol / 24 h / 70 °C 2: triethylamine / dichloromethane / 8 h / -5 °C / Inert atmosphere 3: N-Bromosuccinimide / acetonitrile / 16 h / 20 °C / Inert atmosphere; UV-irradiation 4: water / tetrahydrofuran / 6 h / Reflux View Scheme
Multi-step reaction with 4 steps 1: caesium carbonate / 2-methyltetrahydrofuran / 24 h / 70 °C 2: triethylamine / dichloromethane / 8 h / -5 °C / Inert atmosphere 3: N-Bromosuccinimide / acetonitrile / 16 h / 20 °C / Inert atmosphere; UV-irradiation 4: water / tetrahydrofuran / 6 h / Reflux View Scheme
Multi-step reaction with 4 steps 1.1: tetrahydrofuran / 0.17 h / 20 °C 1.2: 8 h / 40 °C 2.1: triethylamine / dichloromethane / 26 h / 0 - 20 °C 3.1: N-Bromosuccinimide / acetonitrile / 68 h / 20 °C / UV-irradiation 4.1: sodium hydrogencarbonate / acetonitrile / 4 h / Reflux View Scheme

N-(4-(4-fluorophenyl)-6-isopropyl-5-methylpyrimidin-2-yl)-N-methylmethanesulfonamide (953776-62-0) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) + N-[4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide (147118-37-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-Bromosuccinimide / acetonitrile / 16 h / 20 °C / Inert atmosphere; UV-irradiation 2: sodium hydrogencarbonate; dimethyl sulfoxide; sodium iodide / 71 h / 20 °C / Inert atmosphere View Scheme

N-[5-(bromomethyl)-4-(4-fluorophenyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (799842-07-2) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) + N-[4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide (147118-37-4)

Conditions	Yield
With sodium hydrogencarbonate; dimethyl sulfoxide; sodium iodide at 20℃; for 71h; Kornblum oxidation; Inert atmosphere;

1-(4-fluorophenyl)-2-methyl-3-isopropylpropan-1,3-dione (1354455-77-8) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) + N-[4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide (147118-37-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: potassium tert-butylate / tert-butyl alcohol / 24 h / 70 °C 2: triethylamine / dichloromethane / 8 h / -5 °C / Inert atmosphere 3: N-Bromosuccinimide / acetonitrile / 16 h / 20 °C / Inert atmosphere; UV-irradiation 4: sodium hydrogencarbonate; dimethyl sulfoxide; sodium iodide / 71 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1: caesium carbonate / 2-methyltetrahydrofuran / 24 h / 70 °C 2: triethylamine / dichloromethane / 8 h / -5 °C / Inert atmosphere 3: N-Bromosuccinimide / acetonitrile / 16 h / 20 °C / Inert atmosphere; UV-irradiation 4: sodium hydrogencarbonate; dimethyl sulfoxide; sodium iodide / 71 h / 20 °C / Inert atmosphere View Scheme

4-(4-fluorophenyl)-6-isopropyl-N,5-dimethylpyrimidin-2-amine (1207460-34-1) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) + N-[4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide (147118-37-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 8 h / -5 °C / Inert atmosphere 2: N-Bromosuccinimide / acetonitrile / 16 h / 20 °C / Inert atmosphere; UV-irradiation 3: sodium hydrogencarbonate; dimethyl sulfoxide; sodium iodide / 71 h / 20 °C / Inert atmosphere View Scheme

1-(4-Fluorophenyl)-3-isopropylpropan-1,3-dione (114433-94-2) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) + N-[4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide (147118-37-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: potassium carbonate / acetone / 48 h / 20 °C / Inert atmosphere 2: potassium tert-butylate / tert-butyl alcohol / 24 h / 70 °C 3: triethylamine / dichloromethane / 8 h / -5 °C / Inert atmosphere 4: N-Bromosuccinimide / acetonitrile / 16 h / 20 °C / Inert atmosphere; UV-irradiation 5: sodium hydrogencarbonate; dimethyl sulfoxide; sodium iodide / 71 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 5 steps 1: potassium carbonate / acetone / 48 h / 20 °C / Inert atmosphere 2: caesium carbonate / 2-methyltetrahydrofuran / 24 h / 70 °C 3: triethylamine / dichloromethane / 8 h / -5 °C / Inert atmosphere 4: N-Bromosuccinimide / acetonitrile / 16 h / 20 °C / Inert atmosphere; UV-irradiation 5: sodium hydrogencarbonate; dimethyl sulfoxide; sodium iodide / 71 h / 20 °C / Inert atmosphere View Scheme

4-methyl-3-oxopentanoic acid benzyl ester (94250-56-3) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: copper(l) chloride; sulfuric acid / methanol / 12 h / 50 °C 2.1: sodium nitrite; nitric acid / dichloromethane / 1 h / 0 °C 3.1: potassium carbonate; acetic acid butyl ester; p-toluenesulfonyl chloride / 2 h / 40 °C 3.2: 12 h / 120 °C 4.1: 5%-palladium/activated carbon; hydrogen / methanol / 5 h / 20 °C 5.1: sodium tetrahydroborate; chloro-trimethyl-silane / tetrahydrofuran / 24 h / Reflux; Inert atmosphere View Scheme

benzyl 6-(4-fluorophenyl)-4-isopropyl-2-oxo-1,2,5,6-tetrahydropyrimidine-5-carboxylate → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium nitrite; nitric acid / dichloromethane / 1 h / 0 °C 2.1: potassium carbonate; acetic acid butyl ester; p-toluenesulfonyl chloride / 2 h / 40 °C 2.2: 12 h / 120 °C 3.1: 5%-palladium/activated carbon; hydrogen / methanol / 5 h / 20 °C 4.1: sodium tetrahydroborate; chloro-trimethyl-silane / tetrahydrofuran / 24 h / Reflux; Inert atmosphere View Scheme

benzyl 4-(4-fluorophenyl)-2-hydroxy-6-isopropylpyrimidine-5-carboxylate → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium carbonate; acetic acid butyl ester; p-toluenesulfonyl chloride / 2 h / 40 °C 1.2: 12 h / 120 °C 2.1: 5%-palladium/activated carbon; hydrogen / methanol / 5 h / 20 °C 3.1: sodium tetrahydroborate; chloro-trimethyl-silane / tetrahydrofuran / 24 h / Reflux; Inert atmosphere View Scheme

benzyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidine-5-carboxylate → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 5%-palladium/activated carbon; hydrogen / methanol / 5 h / 20 °C 2: sodium tetrahydroborate; chloro-trimethyl-silane / tetrahydrofuran / 24 h / Reflux; Inert atmosphere View Scheme

Methyl 4-methyl-3-oxopentanoate (42558-54-3) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: 150 °C 2.1: copper(l) chloride; sulfuric acid / methanol / 12 h / 50 °C 3.1: sodium nitrite; nitric acid / dichloromethane / 1 h / 0 °C 4.1: potassium carbonate; acetic acid butyl ester; p-toluenesulfonyl chloride / 2 h / 40 °C 4.2: 12 h / 120 °C 5.1: 5%-palladium/activated carbon; hydrogen / methanol / 5 h / 20 °C 6.1: sodium tetrahydroborate; chloro-trimethyl-silane / tetrahydrofuran / 24 h / Reflux; Inert atmosphere View Scheme
Multi-step reaction with 5 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 5.1: diisobutylaluminium hydride / toluene / 1.5 h / -15 - 0 °C View Scheme
Multi-step reaction with 5 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 5.1: diisobutylaluminium hydride / toluene / 1.5 h / -15 - 0 °C View Scheme
Multi-step reaction with 5 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 4.1: sodium hydroxide / ethanol / 0.5 h / 82 °C 5.1: potassium borohydride / tetrahydrofuran / 0.08 h / Cooling with ice 5.2: 4.08 h / 74 °C View Scheme

4-fluorobenzaldehyde (459-57-4) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Multi-step reaction with 5 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 5.1: diisobutylaluminium hydride / toluene / 1.5 h / -15 - 0 °C View Scheme
Multi-step reaction with 5 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 5.1: diisobutylaluminium hydride / toluene / 1.5 h / -15 - 0 °C View Scheme
Multi-step reaction with 5 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 4.1: sodium hydroxide / ethanol / 0.5 h / 82 °C 5.1: potassium borohydride / tetrahydrofuran / 0.08 h / Cooling with ice 5.2: 4.08 h / 74 °C View Scheme

methyl 4-(4-fluorophenyl)-6-isopropyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Multi-step reaction with 4 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 4.1: diisobutylaluminium hydride / toluene / 1.5 h / -15 - 0 °C View Scheme
Multi-step reaction with 4 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 4.1: diisobutylaluminium hydride / toluene / 1.5 h / -15 - 0 °C View Scheme
Multi-step reaction with 4 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 3.1: sodium hydroxide / ethanol / 0.5 h / 82 °C 4.1: potassium borohydride / tetrahydrofuran / 0.08 h / Cooling with ice 4.2: 4.08 h / 74 °C View Scheme

4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-3,4-dihydropyrimidine-2(1H)-one → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Multi-step reaction with 3 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 3.1: diisobutylaluminium hydride / toluene / 1.5 h / -15 - 0 °C View Scheme
Multi-step reaction with 3 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 3.1: diisobutylaluminium hydride / toluene / 1.5 h / -15 - 0 °C View Scheme
Multi-step reaction with 3 steps 1.1: potassium carbonate; p-toluenesulfonyl chloride / acetic acid butyl ester / 0.5 h / 45 °C 1.2: 3 h / 125 °C 2.1: sodium hydroxide / ethanol / 0.5 h / 82 °C 3.1: potassium borohydride / tetrahydrofuran / 0.08 h / Cooling with ice 3.2: 4.08 h / 74 °C View Scheme

2-chloro-4-(4-fluoro-phenyl)-6-isopropyl-pyrimidine-5-carboxylic acid methyl ester (488798-38-5) → N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydride / mineral oil; acetonitrile / 0.08 h 1.2: 7 h / Reflux 2.1: diisobutylaluminium hydride / toluene / 1.5 h / -15 - 0 °C View Scheme

N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → N-[4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide (147118-37-4)

Conditions	Yield
With 1-methyl-1H-imidazole; [2,2]bipyridinyl; tetrakis(acetonitrile)copper(I) trifluoromethanesulfonate; 9-azabicyclo<3.3.1>nonane-N-oxyl In acetonitrile at 20 - 50℃; for 2h; Sealed tube;	99%
With fluorosulfonyl fluoride; potassium carbonate; dimethyl sulfoxide at 20℃; for 2h; Sealed tube; chemoselective reaction;	99%
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; copper(II) nitrate trihydrate In 2-methyltetrahydrofuran at 40℃; for 18h; Temperature; Reagent/catalyst; Solvent;	99%

N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → N-[5-(bromomethyl)-4-(4-fluorophenyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (799842-07-2)

Conditions	Yield
With phosphorus tribromide In toluene; acetonitrile at 10 - 20℃; for 1h; Inert atmosphere;	99%
With phosphorus tribromide In dichloromethane at 0 - 10℃; for 1h;	90.6%
With phosphorus tribromide In dichloromethane at 20℃; for 1h;	82%

N,N-dimethyl-formamide (68-12-2, 33513-42-7) + N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → (4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidin-5-yl)methyl formate

Conditions	Yield
With fluorosulfonyl fluoride; caesium carbonate at 20℃; for 12h; Sealed tube;	99%

triphenylsulfonium trifluoromethanesulfonate (66003-78-9) + N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → N-(4-(4-fluorophenyl)-6-isopropyl-5-(phenoxymethyl)pyrimidin-2-yl)-N-methylmethanesulfonamide

Conditions	Yield
With cesium hydroxide In 1,4-dioxane at 50℃; for 24h; Inert atmosphere; Glovebox;	99%

triphenylphosphine (603-35-0) + N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → [4-[4-fluorophenyl-6-(1-methylethyl)-2-[N-methyl-(N-methanesulfonyl)amino]]-5-pyrimidinyl]methylphenyltriphenylphosphonium bromide

Conditions	Yield
With hydrogen bromide In acetonitrile Solvent; Reflux;	98%

triphenylphosphonium tetrafluoroborate + N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → ((4-p-fluorophenyl-6-isopropyl-2-(N-methylmethylsulfonylamino)-5-pyrimidyl)methyl)triphenylphosphonium tetrafluoroborate

Conditions	Yield
In acetonitrile for 24h; Reflux;	97%

ethyl 5-(bromomethyl)-1,3-diphenyl-1H-pyrazole-4-carboxylate (191419-22-4) + N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → ethyl 5-(((4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidin-5-yl)methoxy)methyl)-1,3-diphenyl-1H-pyrazole-4-carboxylate

Conditions	Yield
With tetrabutylammomium bromide; potassium hydroxide In tetrahydrofuran at 20℃;	95%

triphenylphosphine hydrobromide (6399-81-1) + N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → [4-[4-fluorophenyl-6-(1-methylethyl)-2-[N-methyl-(N-methanesulfonyl)amino]]-5-pyrimidinyl]methylphenyltriphenylphosphonium bromide

Conditions	Yield
In toluene for 10h; Reflux;	94%
In toluene for 10h; Reflux;	83%

silver(I) trifluoromethanethiolate (811-68-7) + N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → N-(4-(4-fluorophenyl)-6-isopropyl-5-(((trifluoromethyl)thio)methyl)pyrimidin-2-yl)-N-methylmethanesulfonamide

Conditions	Yield
With tetra-(n-butyl)ammonium iodide In toluene at 80℃; for 10h; Schlenk technique; Inert atmosphere;	93%

tributylphosphine (998-40-3) + trifluoroacetic anhydride (407-25-0) + N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → ((4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethyl-sulfonamido)pyrimidin-5-yl)methyl)tributylphosphonium 2,2,2-trifluoro-acetate

Conditions	Yield
Stage #1: trifluoroacetic anhydride; N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide With triethylamine In acetic acid butyl ester at 20 - 60℃; Stage #2: tributylphosphine In acetic acid butyl ester for 2h; Product distribution / selectivity; Heating / reflux;	90%

N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → N-[5-chloromethyl-4-(4-fluorophenyl)-6-isopropyl-pyrimidin-2-yl]-N-methyl-methanesulfonamide (925422-06-6)

Conditions	Yield
With methanesulfonyl chloride; triethylamine In dichloromethane at 0 - 25℃; for 5h;	88%

Ag(1+)*CF3S(1-)*(x)C2H3N + N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → N-(4-(4-fluorophenyl)-6-isopropyl-5-(((trifluoromethyl)thio)methyl)pyrimidin-2-yl)-N-methylmethanesulfonamide

Conditions	Yield
With 1,2-Diiodoethane; tetra-(n-butyl)ammonium iodide; triphenylphosphine In N,N-dimethyl-formamide; acetonitrile at 80℃; for 0.25h; Inert atmosphere; Sealed tube;	87%

tetramethylammonium trifluoromethylselenate(0) (75264-92-5) + N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → N-(4-(4-fluorophenyl)-6-isopropyl-5-(((trifluoromethyl)selanyl)methyl)pyrimidin-2-yl)-N-methylmethanesulfonamide

Conditions	Yield
With calcium chloride In acetonitrile at 80℃; for 2h; Time; Inert atmosphere; Sealed tube; Glovebox;	87%

diphenylphosphinous acid methyl ester (4020-99-9) + N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → N-(5-((diphenylphosphoryl)methyl)-4-(4-fluorophenyl)- 6-isopropylpyrimidin-2-yl)-N-methylmethansulfonamide (289042-10-0)

Conditions	Yield
Stage #1: N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide With phosphorus tribromide In acetonitrile at 20℃; Stage #2: diphenylphosphinous acid methyl ester at 60℃;	86%

N-[5-(bromomethyl)-4-(4-fluorophenyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (799842-07-2) + N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → C32H38F2N6O5S2

Conditions	Yield
With potassium carbonate In toluene for 12h; Reflux;	82.4%

sodium phenoxide (139-02-6) + N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → N-(4-(4-fluorophenyl)-6-isopropyl-5-(phenoxymethyl)pyrimidin-2-yl)-N-methylmethanesulfonamide

Conditions	Yield
Stage #1: N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide With 1,2-Diiodoethane; N,N-dimethyl-formamide; triphenylphosphine at 20℃; for 0.0166667h; Sealed tube; Inert atmosphere; Stage #2: sodium phenoxide at 20℃; Sealed tube; Inert atmosphere;	77%

(trifluoromethyl)trimethylsilane (81290-20-2) + N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → N-(4-(4-fluorophenyl)-6-isopropyl-5-((trifluoromethoxy)methyl)pyrimidin-2-yl)-N-methylmethanesulfonamide

Conditions	Yield
With potassium fluoride; 2-fluoropyridine; silver trifluoromethanesulfonate; Selectfluor In ethyl acetate at 20℃; for 12h; Glovebox; Inert atmosphere;	76%

trimethyl(pentafluoroethyl)silane (124898-13-1) + N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → N-(4-(4-fluorophenyl)-6-isopropyl-5-((perfluoroethoxy)methyl)pyrimidin-2-yl)-N-methylmethanesulfonamide

Conditions	Yield
With potassium fluoride; 2-fluoropyridine; silver trifluoromethanesulfonate; lithium trifluoromethanesulfonate; Selectfluor In ethyl acetate at 20℃; for 12h; Inert atmosphere;	64%

N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → N-(5-(fluoromethyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide

Conditions	Yield
With potassium 2-(difluoro(trifluoromethoxy)methoxy)-2,2-difluoroacetate; tetramethylammonium fluoride at 150℃; for 5h; Glovebox; Inert atmosphere; Schlenk technique; Sealed tube;	57%

N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → [4-(4-fluorophenyl)-2-methylamino-6-(1-methylethyl)-pyrimidin-5-yl]methanol

Conditions	Yield
With acetone; lithium diisopropyl amide In tetrahydrofuran at -10℃; for 4.5h; Temperature;	49.6%

acetone (67-64-1) + N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (147118-36-3) → [4-(4-fluorophenyl)-2-[(2-hydroxy-2-methylpropyl)sulfonyl(methyl)amino]-6-(1-methylethyl)-pyrimidin-5-yl]methanol

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran at -10℃; for 4.5h; Temperature;	49.6%

Upstream product

• 147118-30-7 ethyl 2-(N-methyl-N-methanesulfonylamino)-4-(4-fluorophenyl)-6-isopropyl-pyrimidin-5-carboxylic acid 
• 459-57-4 4-fluorobenzaldehyde 
• 122930-45-4 (E)-2-<(4-fluorophenyl)methylene>-4-methyl-3-oxopentanoic acid ethyl ester 
• 7152-15-0 ethyl 4-methyl-3-oxo-pentanoate 
• 147118-32-9 5-ethoxycarbonyl-6-(4'-fluorophenyl)-4-isopropyl-2-(methylamino)pyrimidine 
• 147118-27-2 ethyl 4-(4-fluorophenyl)-2-(methylsulfanyl)-6-(propan-2-yl)-pyrimidine-5-carboxylate 
• 147118-28-3 ethyl 4-(4-fluorophenyl)-6-isopropyl-2-(methylsulfonyl)pyrimidine-5-carboxylate 
• 289042-11-1 methyl 4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulphonyl-N-methylamino)pyrimidine-5-carboxylate 
• 147118-37-4 N-[4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide 
• 799842-07-2 N-[5-(bromomethyl)-4-(4-fluorophenyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide 
• 953776-62-0 N-(4-(4-fluorophenyl)-6-isopropyl-5-methylpyrimidin-2-yl)-N-methylmethanesulfonamide 
• 114433-94-2 1-(4-Fluorophenyl)-3-isopropylpropan-1,3-dione 
• 1207460-34-1 4-(4-fluorophenyl)-6-isopropyl-N,5-dimethylpyrimidin-2-amine 
• 1354455-77-8 1-(4-fluorophenyl)-2-methyl-3-isopropylpropan-1,3-dione 

Downstream Products

• 147118-37-4 N-[4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide 
• 147118-39-6 methyl (3R,6E)-7-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamido)-6-(propan-2-yl)pyrimidin-5-yl]-3-hydroxy-5-oxohept-6-enoate 
• 147118-40-9 (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid methyl ester 
• 147118-38-5 7-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesulfonamido)-pyrimidin-5-yl)-(3R)-3-tert-butyldimethylsiloxy-5-oxo-(E)-6-heptenoic acid methyl ester 
• 799842-07-2 N-[5-(bromomethyl)-4-(4-fluorophenyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide 
• 289042-10-0 N-(5-((diphenylphosphoryl)methyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide 
• 925421-83-6 5-(methanesulfonyl)methyl-4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidine 
• 925421-81-4 5-(trifluoroacetyloxy)methyl-4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidine 
• 289042-12-2 2-[(4R,6S)-6-[(E)-2-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamido)-6-(isopropyl)pyrimidin-5-yl]vinyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetic acid tert butyl ester 
• 956034-90-5 N-((5-(1H-benzo[d]imidazol-2-ylthio)methyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methyimethanesulfonamide 
• 956034-92-7 N-{4-(4-fluorophenyl)-6-isopropyl-5-[(1-methyl-1H-benzo[d]imidazol-2-ylsulfonyl)methyl]pyrimidin-2-yl}-N-methylmethanesulfonamide 
• 1221497-92-2 dimethyl [4-(4-fluorophenyl)-6-isopropyl-2-[methyl (methylsulfonyl) amino]pyrimidine-5-ylmethyl]phosphonate 
• 1344117-75-4 N-[4-(4-fluorophenyl)-5-{[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl}-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide 
• 1344117-77-6 N-[4-(4-fluorophenyl)-5-{[(5-methyl-1,3,4-thiadiazol-2-yl)sulfonyl]methyl}-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethane sulfonamide 

Relevant articles and documents

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.

Method for preparing rosuvastatin calcium intermediate

The invention discloses a preparation method for synthesizing a rosuvastatin calcium intermediate. The method comprises the following steps: taking 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonyl-2-(N-methyl-N-methane sulfonamide) pyrimidine ester shown as formula (II) as a raw material; adding a metal borohydride, in an inert organic solvent, adding BF3 at the temperature of -20 DEG Cto 20 DEG C; raising the temperature to 40-100 DEG C and reacting; treating an obtained reacted solution A, and dissolving obtained 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonyl-2-(N-methyl-N-methanesulfonamido) pyrimidine-5-methanol shown as formula (III) in an organic solvent; adding a catalyst and a co-catalyst, reacting fully at 20 to 100 DEG C at the air or oxygen atmosphere to obtain a reaction solution B, and carrying out aftertreatment on the reaction solution B to obtain 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonyl-2-(N-methyl-N-methane sulfonamide) pyrimidine-5-formaldehyde as shown in formula (IV). The method is mild in condition and simple in aftertreatment, the production cost is reduced, and the molar yield of the product is high.

A method for preparing a rosuvastatin calcium intermediate

The invention relates to the technical field of pharmaceutical chemistry, particularly the field of process optimization and cost control for pharmaceutical intermediate preparation, and more particularly relates to an impurity in preparation of a rosuvastatin calcium intermediate and a method for synthesizing the intermediate from the impurity. A compound I' is reacted with ozone and a reductantto obtain a compound IV and an important intermediate III, the compound IV is further subjected to reduction and substitution to prepare another intermediate II important in preparation of the rosuvastatin calcium intermediate, and the compound II and the compound III are adopted to prepare an intermediate compound I. Through recovery and utilization of the impurity compound I', the preparation cost of the compound I is significantly reduced. The method is simple in process and suitable for industrial large-scale production.