TAK-733

Base Information

• Chemical Name: TAK-733
• CAS No.: 1035555-63-5
• Molecular Formula: C17H15F2IN4O4
• Molecular Weight: 504.232
• Hs Code.: 2933399990
• Mol file: 1035555-63-5.mol

Synonyms:TAK-733

Chemical Property of TAK-733

Chemical Property:

• Boiling Point: 530.5±60.0 °C(Predicted)
• PKA: 13.72±0.20(Predicted)
• PSA: 109.38000
• Density: 1.91±0.1 g/cm3(Predicted)
• LogP: 1.14780
• Solubility.: ≥25.2 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O

Purity/Quality:

98%,99%, ^*data from raw suppliers

(R)-3-(2,3-Dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione 95% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: TAK-733 is a potent and selective MEK allosteric site inhibitor for MEK1 with IC50 of 3.2 nM, inactive to Abl1, AKT3, c-RAF, CamK1, CDK2, c-Met, etc. Phase 1.

Technology Process of TAK-733

There total 16 articles about TAK-733 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: 84.0%

(R)-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido-[2,3-d]pyrimidine-4,7(3H,8H)-dione (1227054-01-4) → TAK-733 (1035555-63-5)

Guidance literature:

With hydrogenchloride; water; In 1-methyl-pyrrolidin-2-one; methanol; at 55 ℃; for 2h; Large scale;

DOI:10.1021/op300198a

Reference yield: 33.0%

(R)-3-(2,3-dihydroxypropyl)-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (1035555-51-1) → TAK-733 (1035555-63-5)

Guidance literature:

With Selectfluor; In N,N-dimethyl-formamide; acetonitrile; at 20 ℃; for 0.166667h;

Reference yield:

3-benzyl-5-(2-fluoro-4-nitrophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (1035556-25-2) → TAK-733 (1035555-63-5)

Guidance literature:

Multi-step reaction with 5 steps

1: acetic acid; zinc

2: hydrogenchloride; potassium iodide; sodium nitrite

3: ammonium formate; palladium(II) hydroxide / 1,4-dioxane

4: potassium carbonate / N,N-dimethyl-formamide

5: Selectfluor / acetonitrile

With hydrogenchloride; ammonium formate; palladium(II) hydroxide; potassium carbonate; acetic acid; Selectfluor; potassium iodide; zinc; sodium nitrite; In 1,4-dioxane; N,N-dimethyl-formamide; acetonitrile;

DOI:10.1016/j.bmcl.2011.01.071

upstream raw materials:

(R)-3-(2,3-dihydroxypropyl)-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

(R)-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido-[2,3-d]pyrimidine-4,7(3H,8H)-dione

3-benzyl-5-(2-fluoro-4-nitrophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

3-benzyl-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

Downstream raw materials:

(R)-3-(2,3-dihydroxypropyl)-5-(4-ethynyl-2-fluorophenylamino)-6-fluoro-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

Refernces

• 1、 Dong, Qing,Dougan, Douglas R.,Gong, Xianchang,Halkowycz, Petro,Jin, Bohan,Kanouni, Toufike,O'Connell, Shawn M.,Scorah, Nicholas,Shi, Lihong,Wallace, Michael B.,Zhou, Feng. "Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer". scheme or table. p. 1315 - 1319. Retrieved 2011/04/16.
• 2、 -. "MAPK/ERK KINASE INHIBITORS". Page/Page column 122-123. . Retrieved 2008/12/07.