1316214-52-4

Basic information

• Product Name: ACY-1215
• Synonyms: Rocilinostat (ACY-1215);2-(Diphenylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]-5-pyrimidinecarboxamide;ACY 63;2-(DiphenylaMino)-N-(7-(hydroxyaMino)-7-oxoheptyl)pyriMidine-5-carboxaMide;5-Pyrimidinecarboxamide, 2-(diphenylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]-;2-(Diphenylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]-5-pyrimidinecarboxamide ACY 1215;Rocilinostat, >=99%;Ricolinostat
• CAS NO: 1316214-52-4
• Molecular Formula: C₂₄H₂₇N₅O₃
• Molecular Weight: 433.50288
• Product Categories: Inhibitor;Inhibitors
• Mol File: 1316214-52-4.mol
• Article Data: 26

Chemical Properties

• Appearance: /
• Density: 1.2±0.1 g/cm³
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 9.47±0.20(Predicted)
• CAS DataBase Reference: ACY-1215(CAS DataBase Reference)
• NIST Chemistry Reference: ACY-1215(1316214-52-4)
• EPA Substance Registry System: ACY-1215(1316214-52-4)

Safety Data

• Hazardous Substances Data: 1316214-52-4(Hazardous Substances Data)

Usage

Description

ACY-1215 is an inhibitor of histone deacetylase 6 (HDAC6; IC50 = 5 nM). It is at least 10-fold less active against other HDACs in enzymatic assays. ACY-1215 shows synergistic activity with the proteasome inhibitor bortezomib against multiple myeloma (MM) cells, inducing protracted endoplasmic reticulum stress and apoptosis. ACY-1215 combined with proteasome inhibitors suppresses tumor growth and increases survival in mice with MM and mantle cell lymphoma xenografts. A multicenter phase I trial examining ACY-1215 combined with the E3 ligase inhibitor lenalidomide and dexamethasone in multiple myeloma found inhibition of HDAC6 in vivo. ACY-1215 also diminishes liver cyst development and fibrosis in a rat model of polycystic liver disease.

Uses

This compound acts as a selective HDAC-6 (histone deacetylase) inihibitor. HDAC is linked to the transcription of DNA in cancers, including multiple myeloma (MM).

Synthetic route

C25H28N4O3 (1316216-07-5) → N-[7-(hydroxyamino)-7-oxo-heptyl]-2-(N-phenylanilino)pyrimidine-5-carboxamide (1316214-52-4)

Conditions	Yield
Stage #1: C25H28N4O3 With sodium hydroxide In methanol; dichloromethane at 0℃; for 0.166667h; Stage #2: With hydroxylamine In methanol; dichloromethane; water at 0 - 20℃; for 0.333333h; Stage #3: With hydrogenchloride In water	48%
Stage #1: C25H28N4O3 With methanol; sodium hydroxide In dichloromethane at 0℃; for 0.166667h; Stage #2: With hydroxylamine In dichloromethane at 0 - 20℃; for 0.333333h;	48%
Stage #1: C25H28N4O3 With sodium hydroxide In methanol; dichloromethane at 0℃; for 0.166667h; Stage #2: With hydroxylamine In methanol; dichloromethane at 0 - 20℃; for 20h;	48%

ethyl 2-chloropyrimidine-5-carboxylate (89793-12-4) → N-[7-(hydroxyamino)-7-oxo-heptyl]-2-(N-phenylanilino)pyrimidine-5-carboxamide (1316214-52-4)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 120 °C 2.1: caesium carbonate / copper(l) iodide / tetraethoxy orthosilicate / 14 h / 140 °C 3.1: water / ethanol / 0.5 h / 60 °C 4.1: N-ethyl-N,N-diisopropylamine; HATU / tetrahydrofuran / 20 °C 5.1: sodium hydroxide / dichloromethane; methanol / 0.17 h / 0 °C 5.2: 0.33 h / 0 - 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 120 °C / Inert atmosphere 2.1: tetraethoxy orthosilicate; copper(l) iodide; caesium carbonate / 14 h / 140 °C / Inert atmosphere 3.1: sodium hydroxide; ethanol / 0.5 h / 60 °C 4.1: HATU; N-ethyl-N,N-diisopropylamine / 20 °C 5.1: sodium hydroxide; methanol / dichloromethane / 0.17 h / 0 °C 5.2: 0.33 h / 0 - 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 120 °C / Inert atmosphere 2.1: copper(l) iodide; caesium carbonate; tetraethoxy orthosilicate / 14 h / 140 °C / Inert atmosphere 3.1: sodium hydroxide / ethanol / 0.5 h / 60 °C 4.1: HATU; N-ethyl-N,N-diisopropylamine / 20 °C 5.1: sodium hydroxide / methanol; dichloromethane / 0.17 h / 0 °C 5.2: 20 h / 0 - 20 °C View Scheme

aniline (62-53-3) → N-[7-(hydroxyamino)-7-oxo-heptyl]-2-(N-phenylanilino)pyrimidine-5-carboxamide (1316214-52-4)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 120 °C 2.1: caesium carbonate / copper(l) iodide / tetraethoxy orthosilicate / 14 h / 140 °C 3.1: water / ethanol / 0.5 h / 60 °C 4.1: N-ethyl-N,N-diisopropylamine; HATU / tetrahydrofuran / 20 °C 5.1: sodium hydroxide / dichloromethane; methanol / 0.17 h / 0 °C 5.2: 0.33 h / 0 - 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 120 °C / Inert atmosphere 2.1: tetraethoxy orthosilicate; copper(l) iodide; caesium carbonate / 14 h / 140 °C / Inert atmosphere 3.1: sodium hydroxide; ethanol / 0.5 h / 60 °C 4.1: HATU; N-ethyl-N,N-diisopropylamine / 20 °C 5.1: sodium hydroxide; methanol / dichloromethane / 0.17 h / 0 °C 5.2: 0.33 h / 0 - 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 120 °C / Inert atmosphere 2.1: copper(l) iodide; caesium carbonate; tetraethoxy orthosilicate / 14 h / 140 °C / Inert atmosphere 3.1: sodium hydroxide / ethanol / 0.5 h / 60 °C 4.1: HATU; N-ethyl-N,N-diisopropylamine / 20 °C 5.1: sodium hydroxide / methanol; dichloromethane / 0.17 h / 0 °C 5.2: 20 h / 0 - 20 °C View Scheme

ethyl 2-(phenylamino)pyrimidine-5-carboxylate (864172-93-0) → N-[7-(hydroxyamino)-7-oxo-heptyl]-2-(N-phenylanilino)pyrimidine-5-carboxamide (1316214-52-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: caesium carbonate / copper(l) iodide / tetraethoxy orthosilicate / 14 h / 140 °C 2.1: water / ethanol / 0.5 h / 60 °C 3.1: N-ethyl-N,N-diisopropylamine; HATU / tetrahydrofuran / 20 °C 4.1: sodium hydroxide / dichloromethane; methanol / 0.17 h / 0 °C 4.2: 0.33 h / 0 - 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: tetraethoxy orthosilicate; copper(l) iodide; caesium carbonate / 14 h / 140 °C / Inert atmosphere 2.1: sodium hydroxide; ethanol / 0.5 h / 60 °C 3.1: HATU; N-ethyl-N,N-diisopropylamine / 20 °C 4.1: sodium hydroxide; methanol / dichloromethane / 0.17 h / 0 °C 4.2: 0.33 h / 0 - 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: copper(l) iodide; caesium carbonate; tetraethoxy orthosilicate / 14 h / 140 °C / Inert atmosphere 2.1: sodium hydroxide / ethanol / 0.5 h / 60 °C 3.1: HATU; N-ethyl-N,N-diisopropylamine / 20 °C 4.1: sodium hydroxide / methanol; dichloromethane / 0.17 h / 0 °C 4.2: 20 h / 0 - 20 °C View Scheme

C19H17N3O2 (1316216-05-3) → N-[7-(hydroxyamino)-7-oxo-heptyl]-2-(N-phenylanilino)pyrimidine-5-carboxamide (1316214-52-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: water / ethanol / 0.5 h / 60 °C 2.1: N-ethyl-N,N-diisopropylamine; HATU / tetrahydrofuran / 20 °C 3.1: sodium hydroxide / dichloromethane; methanol / 0.17 h / 0 °C 3.2: 0.33 h / 0 - 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydroxide; ethanol / 0.5 h / 60 °C 2.1: HATU; N-ethyl-N,N-diisopropylamine / 20 °C 3.1: sodium hydroxide; methanol / dichloromethane / 0.17 h / 0 °C 3.2: 0.33 h / 0 - 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydroxide / ethanol / 0.5 h / 60 °C 2.1: HATU; N-ethyl-N,N-diisopropylamine / 20 °C 3.1: sodium hydroxide / methanol; dichloromethane / 0.17 h / 0 °C 3.2: 20 h / 0 - 20 °C View Scheme

C17H13N3O2 (1316216-06-4) → N-[7-(hydroxyamino)-7-oxo-heptyl]-2-(N-phenylanilino)pyrimidine-5-carboxamide (1316214-52-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine; HATU / tetrahydrofuran / 20 °C 2.1: sodium hydroxide / dichloromethane; methanol / 0.17 h / 0 °C 2.2: 0.33 h / 0 - 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: HATU; N-ethyl-N,N-diisopropylamine / 20 °C 2.1: sodium hydroxide; methanol / dichloromethane / 0.17 h / 0 °C 2.2: 0.33 h / 0 - 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: HATU; N-ethyl-N,N-diisopropylamine / 20 °C 2.1: sodium hydroxide / methanol; dichloromethane / 0.17 h / 0 °C 2.2: 20 h / 0 - 20 °C View Scheme

2-hydroxy-pyrimidine-5-carboxylic acid ethyl ester (95928-49-7) → N-[7-(hydroxyamino)-7-oxo-heptyl]-2-(N-phenylanilino)pyrimidine-5-carboxamide (1316214-52-4)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: dmap; trichlorophosphate / 1.5 h / Reflux 1.2: pH 7 2.1: potassium carbonate / N,N-dimethyl-formamide / 120 °C 3.1: caesium carbonate / copper(l) iodide / tetraethoxy orthosilicate / 14 h / 140 °C 4.1: water / ethanol / 0.5 h / 60 °C 5.1: N-ethyl-N,N-diisopropylamine; HATU / tetrahydrofuran / 20 °C 6.1: sodium hydroxide / dichloromethane; methanol / 0.17 h / 0 °C 6.2: 0.33 h / 0 - 20 °C View Scheme
Multi-step reaction with 6 steps 1.1: trichlorophosphate; dmap / 1.5 h / Reflux 1.2: pH 7 2.1: potassium carbonate / N,N-dimethyl-formamide / 120 °C / Inert atmosphere 3.1: tetraethoxy orthosilicate; copper(l) iodide; caesium carbonate / 14 h / 140 °C / Inert atmosphere 4.1: sodium hydroxide; ethanol / 0.5 h / 60 °C 5.1: HATU; N-ethyl-N,N-diisopropylamine / 20 °C 6.1: sodium hydroxide; methanol / dichloromethane / 0.17 h / 0 °C 6.2: 0.33 h / 0 - 20 °C View Scheme

4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran (96042-30-7) → N-[7-(hydroxyamino)-7-oxo-heptyl]-2-(N-phenylanilino)pyrimidine-5-carboxamide (1316214-52-4)

Conditions	Yield
With sodium hydroxide; hydroxylamine

iodobenzene (591-50-4) → N-[7-(hydroxyamino)-7-oxo-heptyl]-2-(N-phenylanilino)pyrimidine-5-carboxamide (1316214-52-4)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: copper(l) iodide; caesium carbonate / 14 h / 140 °C / Inert atmosphere 2.1: sodium hydroxide / ethanol / 0.5 h / 60 °C 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 20 °C 4.1: sodium hydroxide / methanol; dichloromethane / 0.17 h / 0 °C 4.2: 0.33 h / 0 - 20 °C View Scheme

methyl 7-aminoheptanoate (39979-08-3) + C17H13N3O2 (1316216-06-4) → N-[7-(hydroxyamino)-7-oxo-heptyl]-2-(N-phenylanilino)pyrimidine-5-carboxamide (1316214-52-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 20 °C 2.1: sodium hydroxide / methanol; dichloromethane / 0.17 h / 0 °C 2.2: 0.33 h / 0 - 20 °C View Scheme

Upstream product

• 96042-30-7 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 
• 39979-08-3 methyl 7-aminoheptanoate 
• 1316216-06-4 C₁₇H₁₃N₃O₂ 
• 591-50-4 iodobenzene 
• 95928-49-7 2-hydroxy-pyrimidine-5-carboxylic acid ethyl ester 
• 1316216-07-5 C₂₅H₂₈N₄O₃ 
• 1316216-05-3 C₁₉H₁₇N₃O₂ 
• 864172-93-0 ethyl 2-(phenylamino)pyrimidine-5-carboxylate 
• 62-53-3 aniline 
• 89793-12-4 ethyl 2-chloropyrimidine-5-carboxylate 

Relevant articles and documents

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