Production Method 1

1115035-61-4

877133-54-5

Reaction Conditions

1.1 Reagents: Pentabromophosphorane Solvents: Chloroform ;  1 h, 60 °C
1.2 8 h, 120 °C; cooled
1.3 Reagents: Sodium hydroxide Solvents: Water

Reference

Discovery of (R)-6-Cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-3-((5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl)-4-hydroxy-5,6-dihydropyran-2-one (PF-00868554) as a Potent and Orally Available Hepatitis C Virus Polymerase Inhibitor

Li, Hui; et al, Journal of Medicinal Chemistry, 2009, 52(5), 1255-1258

Production Method 2

1035267-63-0

877133-54-5

Reaction Conditions

1.1 Reagents: Phosphorus tribromide Solvents: Dichloromethane

Reference

Synthetic route optimization of PF-00868554, an HCV polymerase inhibitor in clinical evaluation

Johnson, Sarah; et al, Synlett, 2010, (5), 796-800

Production Method 3

1115035-61-4

877133-54-5

Reaction Conditions

1.1 Reagents: Phosphoric tribromide Solvents: Dimethylformamide ;  120 °C

Reference

Synthetic route optimization of PF-00868554, an HCV polymerase inhibitor in clinical evaluation

Johnson, Sarah; et al, Synlett, 2010, (5), 796-800

Production Method 4

1115035-61-4

877133-54-5

Reaction Conditions

1.1 Reagents: Phosphoric tribromide ;  90 min, 130 °C

Reference

Di-substituted pyridinyl aminohydantoins as potent and highly selective human β-secretase (BACE1) inhibitors

Malamas, Michael S.; et al, Bioorganic & Medicinal Chemistry, 2010, 18(2), 630-639

Production Method 5

542-05-2

877133-54-5

Reaction Conditions

1.1 Reagents: Sulfuric acid ;  100 °C
1.2 Reagents: Acetic acid ,  Sodium bicarbonate Solvents: Water ;  100 °C; 100 °C → rt
1.3 Reagents: Chloroform ;  reflux
1.4 Reagents: Ammonia Solvents: Water ;  50 °C
1.5 Reagents: Pentabromophosphorane ;  120 °C

Reference

A New Fluorogenic Small-Molecule Labeling Tool for Surface Diffusion Analysis and Advanced Fluorescence Imaging of β-Site Amyloid Precursor Protein-Cleaving Enzyme 1 Based on Silicone Rhodamine: SiR-BACE1

Karch, Sandra ; et al, Journal of Medicinal Chemistry, 2018, 61(14), 6121-6139

Production Method 6

542-05-2

877133-54-5

Reaction Conditions

1.1 Reagents: Sulfuric acid ;  100 °C
1.2 Reagents: Sodium sulfate ;  100 °C
1.3 Reagents: Hydrochloric acid ;  100 °C
1.4 Reagents: Ammonium hydroxide ;  50 °C
2.1 Reagents: Phosphoric tribromide Solvents: Dimethylformamide ;  120 °C

Reference

Synthetic route optimization of PF-00868554, an HCV polymerase inhibitor in clinical evaluation

Johnson, Sarah; et al, Synlett, 2010, (5), 796-800

Production Method 7

542-05-2

877133-54-5

Reaction Conditions

1.1 Reagents: Sulfuric acid
1.2 Reagents: Acetic acid ,  Sodium carbonate
1.3 Reagents: Hydrochloric acid
2.1 Reagents: Ammonium hydroxide
2.2 Reagents: Methyl iodide ,  Lithium diisopropylamide Solvents: Tetrahydrofuran
3.1 Reagents: Phosphoric tribromide ;  90 min, 130 °C

Reference

Di-substituted pyridinyl aminohydantoins as potent and highly selective human β-secretase (BACE1) inhibitors

Malamas, Michael S.; et al, Bioorganic & Medicinal Chemistry, 2010, 18(2), 630-639

Production Method 8

114960-28-0

877133-54-5

Reaction Conditions

1.1 Reagents: Sulfuric acid ,  Nitric acid
2.1 Reagents: Acetyl bromide Solvents: Acetic acid
3.1 Reagents: Phosphorus tribromide Solvents: Dichloromethane

Reference

Synthetic route optimization of PF-00868554, an HCV polymerase inhibitor in clinical evaluation

Johnson, Sarah; et al, Synlett, 2010, (5), 796-800

Production Method 9

14774-14-2

877133-54-5

Reaction Conditions

1.1 Reagents: Ammonium hydroxide
1.2 Reagents: Methyl iodide ,  Lithium diisopropylamide Solvents: Tetrahydrofuran
2.1 Reagents: Phosphoric tribromide ;  90 min, 130 °C

Reference

Di-substituted pyridinyl aminohydantoins as potent and highly selective human β-secretase (BACE1) inhibitors

Malamas, Michael S.; et al, Bioorganic & Medicinal Chemistry, 2010, 18(2), 630-639

Production Method 10

14774-14-2

877133-54-5

Reaction Conditions

1.1 Reagents: Ammonia Solvents: Water ;  overnight, 50 °C; 50 °C → rt
2.1 Reagents: Pentabromophosphorane Solvents: Chloroform ;  1 h, 60 °C
2.2 8 h, 120 °C; cooled
2.3 Reagents: Sodium hydroxide Solvents: Water

Reference

Discovery of (R)-6-Cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-3-((5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl)-4-hydroxy-5,6-dihydropyran-2-one (PF-00868554) as a Potent and Orally Available Hepatitis C Virus Polymerase Inhibitor

Li, Hui; et al, Journal of Medicinal Chemistry, 2009, 52(5), 1255-1258

Production Method 11

457919-59-4

877133-54-5

Reaction Conditions

1.1 Reagents: Acetyl bromide Solvents: Acetic acid
2.1 Reagents: Phosphorus tribromide Solvents: Dichloromethane

Reference

Synthetic route optimization of PF-00868554, an HCV polymerase inhibitor in clinical evaluation

Johnson, Sarah; et al, Synlett, 2010, (5), 796-800

Production Method 12

935-28-4

877133-54-5

Reaction Conditions

1.1 Reagents: m-Chloroperbenzoic acid Solvents: Chloroform
2.1 Reagents: Sulfuric acid ,  Nitric acid
3.1 Reagents: Acetyl bromide Solvents: Acetic acid
4.1 Reagents: Phosphorus tribromide Solvents: Dichloromethane

Reference

Synthetic route optimization of PF-00868554, an HCV polymerase inhibitor in clinical evaluation

Johnson, Sarah; et al, Synlett, 2010, (5), 796-800

Production Method 13

2402-78-0

925-90-6

877133-54-5

Reaction Conditions

1.1 Catalysts: Dichloro[1,1′-(1,3-propanediyl)bis[1,1-diphenylphosphine-κP]]nickel Solvents: Diethyl ether
2.1 Reagents: m-Chloroperbenzoic acid Solvents: Chloroform
3.1 Reagents: Sulfuric acid ,  Nitric acid
4.1 Reagents: Acetyl bromide Solvents: Acetic acid
5.1 Reagents: Phosphorus tribromide Solvents: Dichloromethane

Reference

Synthetic route optimization of PF-00868554, an HCV polymerase inhibitor in clinical evaluation

Johnson, Sarah; et al, Synlett, 2010, (5), 796-800

4-Bromo-2,6-diethylpyridine Raw materials

• 2,6-Dichloropyridine
• Ethylmagnesium Bromide (3M in Et2O)
• 4H-Pyran-4-one,2,6-diethyl-
• 2,6-Diethylpyridine
• 1,3-Acetonedicarboxylic acid
• Pyridine, 2,6-diethyl-4-nitro-, 1-oxide
• 2,6-Diethylpyridin-4-ol

4-Bromo-2,6-diethylpyridine Preparation Products

• 4-Bromo-2,6-diethylpyridine (877133-54-5)

• 1. Fe/Fe3C@C nanoparticles encapsulated in N-doped graphene–CNTs framework as an efficient bifunctional oxygen electrocatalyst for robust rechargeable Zn–air batteries?
  Zhiyan Chen,Nan Wu,Yaobing Wang,Bing Wang,Yingde Wang J. Mater. Chem. A, 2018,6, 516-526
• 2. Dissociative dynamics of O2 on Ag(110)?
  Ivor Lon?ari? Phys. Chem. Chem. Phys., 2015,17, 9436-9445
• 3. Exceptional activity of sub-nm Pt clusters on CdS for photocatalytic hydrogen production: a combined experimental and first-principles study?
  Qiyuan Wu,Shangmin Xiong,Peichuan Shen,Shen Zhao,Alexander Orlov Catal. Sci. Technol., 2015,5, 2059-2064
• 4. Fatty acid eutectic mixtures and derivatives from non-edible animal fat as phase change materials?
  Pau Gallart-Sirvent,Marc Martín,Gemma Villorbina,Mercè Balcells,Aran Solé,Luisa F. Cabeza,Ramon Canela-Garayoa RSC Adv., 2017,7, 24133-24139
• 5. Evidence of field induced slow magnetic relaxation in cis-[Co(hfac)2(H2O)2] exhibiting tri-axial anisotropy with a negative axial component?
  Denis V. Korchagin,Elena A. Yureva,Alexander V. Akimov,Eugenii Ya. Misochko,Gennady V. Shilov,Artem D. Talantsev,Roman B. Morgunov,Alexander A. Shakin,Sergey M. Aldoshin,Boris S. Tsukerblat Dalton Trans., 2017,46, 7540-7548

• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Pyridines and derivatives Pyridines and derivatives
• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Pyridines and derivatives

• 2055841-93-3(4-Bromo-2,6-diethylpyridine hydrochloride)
• 1643563-99-8(4-Bromo-(2-methyl-6-ethyl-d8)-pyridine)
• 1563532-13-7(4-Bromo-2-isobutylpyridine)
• 886372-51-6((4-Bromo-6-methyl-pyridin-2-YL)-acetonitrile)
• 1823567-27-6(Pyridine, 4-bromo-2-butyl-)
• 155887-27-7(Pyridine, 4-bromo-2-ethyl-6-methyl-)
• 98420-99-6(4-Bromo-2-propylpyridine)
• 1379368-18-9(4-Bromo-2,6-dicyclopropylpyridine)
• 156761-88-5(4-Bromo-2-ethylpyridine)
• 908267-63-0(4-bromo-2-(propan-2-yl)pyridine)