MRK 560

Base Information

• Chemical Name: MRK 560
• CAS No.: 677772-84-8
• Molecular Formula: C19H17ClF5NO4S2
• Molecular Weight: 517.91800
• Mol file: 677772-84-8.mol

Synonyms:

Chemical Property of MRK 560

Chemical Property:

• Boiling Point: 580.1±60.0 °C(Predicted)
• PKA: 5.97±0.40(Predicted)
• PSA: 97.07000
• Density: 1.57±0.1 g/cm3(Predicted)
• LogP: 7.22170
• Solubility.: <51.79mg/ml in DMSO; <25.9mg/ml in ethanol

Purity/Quality:

98% ^*data from raw suppliers

MRK560 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: MRK-560 is a potent inhibitor of γ-secretase (IC50 = 0.65 nM). In vivo, MRK-560 (1-10 mg/kg) reduces diethanolamine-soluble amyloid-β (1-40) (Aβ40) levels in APP-YAC transgenic mouse brain. MRK-560 reduces brain and cerebrospinal fluid Aβ40 levels in rats (ED50s = 6 and 10 mg/kg, respectively). It also decreases brain-soluble Aβ40 and Aβ42 levels and recovers hippocampal long-term potentiation in the Tg2576 transgenic mouse model of Alzheimer''s disease.
• Uses: MRK 560 acts as a y-secretase inhibitor that is orally bioavailable and potent and may be used in a therapeutic strategy to counter low amyloid (β) production in Alheimer’s disease.

Technology Process of MRK 560

There total 7 articles about MRK 560 which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield:

cis-4-(4-chlorobenzenesulfonyl)-4-(2,5-difluorophenyl)cyclohexylamine → trifluoromethanesulfonic acid, N-[4-(4-chlorobenzenesulfonyl)-4-(2,5-difluorophenyl)-cyclohexyl]-amide (677772-84-8)

Guidance literature:

cis-4-(4-chlorobenzenesulfonyl)-4-(2,5-difluorophenyl)cyclohexylamine; With trifluoromethylsulfonic anhydride; triethylamine; In dichloromethane; at 0 ℃; for 2.5h;

With sodium hydroxide; In dichloromethane; water;

Reference yield:

4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexanone (471903-20-5) → MRK-560 (677772-84-8)

Guidance literature:

Multi-step reaction with 5 steps

1: NaBH₄ / ethanol / 10 °C

2: Et₃N / CH₂Cl₂ / -50 °C

3: NaN₃ / dimethylformamide / 90 °C

4: Ph₃P; H₂O / tetrahydrofuran

5: Et₃N / CH₂Cl₂

With sodium tetrahydroborate; sodium azide; water; triethylamine; triphenylphosphine; In tetrahydrofuran; ethanol; dichloromethane; N,N-dimethyl-formamide;

DOI:10.1016/j.bmcl.2005.10.009

Reference yield:

trans-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexanol (471903-41-0) → MRK-560 (677772-84-8)

Guidance literature:

Multi-step reaction with 4 steps

1: Et₃N / CH₂Cl₂ / -50 °C

2: NaN₃ / dimethylformamide / 90 °C

3: Ph₃P; H₂O / tetrahydrofuran

4: Et₃N / CH₂Cl₂

With sodium azide; water; triethylamine; triphenylphosphine; In tetrahydrofuran; dichloromethane; N,N-dimethyl-formamide;

DOI:10.1016/j.bmcl.2005.10.009

upstream raw materials:

4-(4-chloro-benzenesulfonyl)-4-(2,5-difluoro-phenyl)-cyclohexylamine

trifluoromethylsulfonic anhydride

4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexanone

trans-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexanol

Refernces

• 1、 Churcher, Ian,Beher, Dirk,Best, Jonathan D.,Castro, Jose L.,Clarke, Earl E.,Gentry, Amy,Harrison, Timothy,Hitzel, Laure,Kay, Euan,Kerrad, Sonia,Lewis, Huw D.,Morentin-Gutierrez, Pablo,Mortishire-Smith, Russell,Oakley, Paul J.,Reilly, Michael,Shaw, Duncan E.,Shearman, Mark S.,Teall, Martin R.,Williams, Susie,Wrigley, Jonathan D.J.. "4-Substituted cyclohexyl sulfones as potent, orally active γ-secretase inhibitors". . p. 280 - 284. Retrieved 2007/10/03.