GDC-0068

Base Information

• Chemical Name: GDC-0068
• CAS No.: 1001264-89-6
• Molecular Formula: C24H32ClN5O2
• Molecular Weight: 458
• Mol file: 1001264-89-6.mol

Synonyms:RG7440;(S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)propan-1-one;

Chemical Property of GDC-0068

Chemical Property:

• Appearance/Colour: Peach Solid
• Melting Point: >106°C (dec.)
• Boiling Point: 669.4±55.0 °C(Predicted)
• PKA: 13.11±0.40(Predicted)
• PSA: 81.59000
• Density: 1.254
• LogP: 3.49480
• Storage Temp.: Hygroscopic, Refrigerator, under inert atmosphere
• Solubility.: Soluble in DMSO.

Purity/Quality:

98% ^*data from raw suppliers

(2S)-2-(4-Chlorophenyl)-1-[4-[(5R,7R)-6,7-dihydro-7-hydroxy-5-methyl-5H-cyclopentapyrimidin-4-yl]-1-piperazinyl]-3-[(1-methylethyl)amino]-1-propanone ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Uses: DC-0068 is a highly selective pan-Akt inhibitor targeting Akt1, Akt2, and Akt3 with IC50 of 5 nM, 18 nM, and 8 nM, respectively. GDC-0068 is a highly selective AKT inhibitor targeting Akt1 , Akt2 and Akt3. Studies have shown its use in combination with vemurafenib (V118500), have demonstrated therapeutic value in the treatment of hyperproliferative disorders such as cancer. (2S)-2-(4-Chlorophenyl)-1-[4-[(5R,7R)-6,7-dihydro-7-hydroxy-5-methyl-5H-cyclopentapyrimidin-4-yl]-1-piperazinyl]-3-[(1-methylethyl)amino]-1-propanone is a highly selective AKT inhibitor targeting Akt1, Akt2 and Akt3. Studies have shown its use in combination with vemurafenib (V118500), have demonstrated therapeutic value in the treatment of hyperproliferative disorders such as cancer.

Technology Process of GDC-0068

There total 45 articles about GDC-0068 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: 90.0%

tert-butyl ((S)-2-(4-chlorophenyl)-3-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl)(isopropyl)carbamate (1001270-64-9) → (2S)-2-(4-chlorophenyl)-1-[4-[(5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]piperazin-1-yl]-3-(propan-2-yiamino)propan-1-one (1001264-89-6)

Guidance literature:

With hydrogenchloride; In 1,4-dioxane; at 20 ℃;

Reference yield:

tert-butyl 4-((5R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-piperazine-1-carboxylate (1001180-15-9) → (2S)-2-(4-chlorophenyl)-1-[4-[(5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]piperazin-1-yl]-3-(propan-2-yiamino)propan-1-one (1001264-89-6)

Guidance literature:

Multi-step reaction with 5 steps

1.1: ethanol; hexane

2.1: lithium hydroxide; water / tetrahydrofuran / 6 h / 20 °C

3.1: hydrogenchloride / 1,4-dioxane / 20 h / 20 °C

4.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 20 °C

4.2: 1 h / 20 °C

5.1: hydrogenchloride / 1,4-dioxane / 20 °C

With hydrogenchloride; lithium hydroxide; water; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; 1,4-dioxane; ethanol; hexane; dichloromethane;

Reference yield:

tert-butyl 4-((5R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-piperazine-1-carboxylate (1001180-18-2) → (2S)-2-(4-chlorophenyl)-1-[4-[(5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]piperazin-1-yl]-3-(propan-2-yiamino)propan-1-one (1001264-89-6)

Guidance literature:

Multi-step reaction with 5 steps

1.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 1.58 h / -78 °C

1.2: 0.5 h / -78 - 20 °C

2.1: formic acid; triethylamine / Ru catalyst / dichloromethane / 18 h

3.1: hydrogenchloride / 1,4-dioxane / 20 h / 20 °C

4.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 20 °C

4.2: 1 h / 20 °C

5.1: hydrogenchloride / 1,4-dioxane / 20 °C

With hydrogenchloride; formic acid; oxalyl dichloride; dimethyl sulfoxide; triethylamine; N-ethyl-N,N-diisopropylamine; Ru catalyst; In 1,4-dioxane; dichloromethane;

upstream raw materials:

tert-butyl ((S)-2-(4-chlorophenyl)-3-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl)(isopropyl)carbamate

(R)-3-methylpentanedioic acid monomethyl ester

tert-butyl 4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]-pyrimidin-4-yl)piperazine-1-carboxylate

4-chlorophenylacetic Acid

Refernces

• 1、 -. "COMBINATIONS OF AKT INHIBITOR COMPOUNDS AND VEMURAFENIB, AND METHODS OF USE". Page/Page column 80-81. . Retrieved 2012/10/18.