MK-8617

Base Information

• Chemical Name: MK-8617
• CAS No.: 1187990-87-9
• Molecular Formula: C24H21N5O4
• Molecular Weight: 443.462
• Mol file: 1187990-87-9.mol

Synonyms:N-[bis(4-methoxyphenyl)methyl]4-hydroxy-2-pyridazin-3-ylpyrimidine-5-carboxamide;

Chemical Property of MK-8617

Chemical Property:

• PKA: 5.54±0.50(Predicted)
• PSA: 119.35000
• Density: 1.32±0.1 g/cm3(Predicted)
• LogP: 3.56670

Purity/Quality:

97% ^*data from raw suppliers

MK-8617 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Uses: MK-8617 is a potent, selective and bioavailable hypoxia-inducible factor prolyl hydroxylase 1-3 (HIF PHD1-3) inhibitor used in the treatment of anemia.

Technology Process of MK-8617

There total 5 articles about MK-8617 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: 87.0%

4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxylic acid (1187992-93-3) + p,p'-dimethoxybenzhydrylamine (19293-62-0) → N-[bis(4-methoxyphenyl)methyl]-4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamide (1187990-87-9)

Guidance literature:

4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxylic acid; With triethylamine; 1,1'-carbonyldiimidazole; In 1-methyl-pyrrolidin-2-one; at 70 ℃; for 1h; Inert atmosphere;

p,p'-dimethoxybenzhydrylamine; In 1-methyl-pyrrolidin-2-one; at 70 ℃; for 0.5h; Inert atmosphere;

DOI:10.1021/acs.jmedchem.6b01242

Reference yield:

2-[(4-methylphenyl)sulfonyl]-2,3-dihydropyridazine-3-carbonitrile (106861-14-7) → N-[bis(4-methoxyphenyl)methyl]-4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamide (1187990-87-9)

Guidance literature:

Multi-step reaction with 5 steps

1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere

2.1: sodium methylate / methanol / 20 °C / Inert atmosphere

2.2: 5 h / Reflux; Inert atmosphere

2.3: 20 °C / Inert atmosphere

3.1: sodium ethanolate / ethanol / 28 h / Reflux; Inert atmosphere

4.1: potassium hydroxide / water; ethanol / 6 h / Inert atmosphere

5.1: 1,1'-carbonyldiimidazole; triethylamine / 1-methyl-pyrrolidin-2-one / 1 h / 70 °C / Inert atmosphere

5.2: 0.5 h / 70 °C / Inert atmosphere

With sodium methylate; sodium ethanolate; 1,8-diazabicyclo[5.4.0]undec-7-ene; triethylamine; 1,1'-carbonyldiimidazole; potassium hydroxide; In tetrahydrofuran; 1-methyl-pyrrolidin-2-one; methanol; ethanol; water;

DOI:10.1021/acs.jmedchem.6b01242

Reference yield:

pyridazine-3-carbonitrile (53896-49-4) → N-[bis(4-methoxyphenyl)methyl]-4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamide (1187990-87-9)

Guidance literature:

Multi-step reaction with 4 steps

1.1: sodium methylate / methanol / 20 °C / Inert atmosphere

1.2: 5 h / Reflux; Inert atmosphere

1.3: 20 °C / Inert atmosphere

2.1: sodium ethanolate / ethanol / 28 h / Reflux; Inert atmosphere

3.1: potassium hydroxide / water; ethanol / 6 h / Inert atmosphere

4.1: 1,1'-carbonyldiimidazole; triethylamine / 1-methyl-pyrrolidin-2-one / 1 h / 70 °C / Inert atmosphere

4.2: 0.5 h / 70 °C / Inert atmosphere

With sodium methylate; sodium ethanolate; triethylamine; 1,1'-carbonyldiimidazole; potassium hydroxide; In 1-methyl-pyrrolidin-2-one; methanol; ethanol; water;

DOI:10.1021/acs.jmedchem.6b01242

upstream raw materials:

4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxylic acid

p,p'-dimethoxybenzhydrylamine

2-[(4-methylphenyl)sulfonyl]-2,3-dihydropyridazine-3-carbonitrile

pyridazine-3-carbonitrile

Downstream raw materials:

N-[bis(4-methoxyphenyl)methyl]-4-hydroxy-2-pyridazin-3-ylpyrimidine-5-carboxamide 1,3-dihydroxy-2-(hydroxymethyl)propan-2-ammonium

N-[bis(4-methoxyphenyl)methyl]-4-hydroxy-2-pyridazin-3-ylpyrimidine-5-carboxamide potassium

N-[bis(4-hydroxyphenyl)methyl]-4-hydroxy-2-pyridazin-3-ylpyrimidine-5-carboxamide