CFI-400945

Base Information

• Chemical Name: CFI-400945
• CAS No.: 1338806-73-7
• Molecular Formula: C₃₃H₃₄N₄O₃
• Molecular Weight: 534.658
• Mol file: 1338806-73-7.mol

Synonyms:CFI-400945;ocifisertib;CFI-400945 (CFI400945;CFI-400945 (free base);Spiro[cyclopropane-1,3'-[3H]indol]-2'(1'H)-one, 2-[3-[(1E)-2-[4-[[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl]phenyl]ethenyl]-1H-indazol-6-yl]-5'-methoxy-, (1R,2S)-

Chemical Property of CFI-400945

Chemical Property:

• Boiling Point: 751.5±60.0 °C(Predicted)
• PKA: 13.09±0.40(Predicted)
• PSA: 79.48000
• Density: 1.32±0.1 g/cm3(Predicted)
• LogP: 5.80440
• Solubility.: insoluble in H2O; ≥109.8 mg/mL in DMSO; ≥93 mg/mL in EtOH

Purity/Quality:

99%+, ^*data from raw suppliers

CFI-400945 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Uses: (1R,?2S)?-2-?[3-?[(1E)?-?2-?[4-?[[(2R,?6S)?-?2,?6-?Dimethyl-?4-?morpholinyl]?methyl]?phenyl]?ethenyl]?-?1H-?indazol-?6-?yl]?-?5''-?methoxy-?spiro[cyclopropane-?1,?3''-?[3H]?indol]?-?2''(1''H)?-?one selectively inhibits polo-like kinase 4 (PLK4), which is a serine/threonine protein kinase that regulates centriole duplication during the cell cycle. PLK4 is a therapeutic target for various cancers.

Technology Process of CFI-400945

There total 18 articles about CFI-400945 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: 48.0%

(1R,2S)-2-(3-iodo-1H-indazol-6-yl)-5'-methoxyspiro[cyclopropane-1,3'-indolin]-2'-one (1247001-86-0) + cis-2,6-dimethyl-4-(4-((E)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl)benzyl)morpholine → (1R,2S)-(E)-2-(3-(4-((cis-2,6-dimethylmorpholino)methyl)styryl)-1H-indazol-6-yl)-5‘-methoxyspiro[cyclopropane-1,3’-indolin]-2-one (1338806-73-7)

Guidance literature:

With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate; In 1,4-dioxane; water; at 85 ℃; for 24h;

DOI:10.1021/jm5005336

Reference yield:

6-bromo-1H-indazole (79762-54-2) → (1R,2S)-(E)-2-(3-(4-((cis-2,6-dimethylmorpholino)methyl)styryl)-1H-indazol-6-yl)-5‘-methoxyspiro[cyclopropane-1,3’-indolin]-2-one (1338806-73-7)

Guidance literature:

Multi-step reaction with 8 steps

1.1: potassium tert-butylate / dimethyl sulfoxide / 0.17 h

1.2: 12 h / 20 - 150 °C

2.1: potassium carbonate; bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 7 h / 80 °C / Inert atmosphere

3.1: potassium carbonate; potassium osmate(VI) dihydrate; potassium hexacyanoferrate(III); 4-[(R)-[(2R,4R,5S)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxy-4-quinolinyl)methoxy]-1-[(R)-[(2R,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxy-4-quinolinyl)methoxy]phthalazine / water; tert-butyl alcohol / 6 h / 0 - 10 °C

4.1: triethylamine / dichloromethane / 0.5 h / 0 - 11 °C

5.1: sodium hydride / mineral oil; tetrahydrofuran / 0.25 h / 0 °C

5.2: 2 h / 0 °C

6.1: potassium tert-butylate; oxygen / dimethyl sulfoxide; tetrahydrofuran / 0 - 20 °C

7.1: potassium carbonate / methanol; N,N-dimethyl-formamide / 6 h / 20 °C

8.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / water; 1,4-dioxane / 24 h / 85 °C

With bis-triphenylphosphine-palladium(II) chloride; potassium osmate(VI) dihydrate; tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium tert-butylate; oxygen; sodium hydride; sodium carbonate; potassium carbonate; 4-[(R)-[(2R,4R,5S)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxy-4-quinolinyl)methoxy]-1-[(R)-[(2R,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxy-4-quinolinyl)methoxy]phthalazine; triethylamine; potassium hexacyanoferrate(III); In tetrahydrofuran; 1,4-dioxane; methanol; 1,2-dimethoxyethane; dichloromethane; water; dimethyl sulfoxide; N,N-dimethyl-formamide; mineral oil; tert-butyl alcohol; 2.1: |Suzuki-Miyaura Coupling;

DOI:10.1021/jm5005336

Reference yield:

cis-2,6-dimethylmorpholine + C27H21N3O3 → (1R*,2S*)-(E)-(2-(3-(4-(cis-2,6-dimethylmorpholino)methyl)styryl)-1H-indazol-6-yl)-5'-methoxyspiro[cyclopropane-1,3'-indolin]-2'-one (1338806-73-7)

Guidance literature:

cis-2,6-dimethylmorpholine; C₂₇H₂₁N₃O₃; With sodium tris(acetoxy)borohydride; acetic acid; In tetrahydrofuran; 1,2-dichloro-ethane; at 20 ℃; for 3h;

With sodium hydrogencarbonate; In tetrahydrofuran; water; 1,2-dichloro-ethane;

upstream raw materials:

(E)-4-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl)benzaldehyde

3-((3-iodo-1H-indazol-6-yl)methylene)-5-methoxyindolin-2-one

(1R,2S)-2-(3-iodo-1H-indazol-6-yl)-5'-methoxyspiro[cyclopropane-1,3'-indolin]-2'-one

6-bromo-1H-indazole

Downstream raw materials:

(1R,2S)-(E)-2-(3-(4-(cis-2,6-dimethylmorpholinomethyl)styryl)-1H-indazol-6-yl)-5'-methoxyspiro[cyclopropane-1,3'-indolin]-2'-one fumarate

(1R,2S)-(E)-2-(3-(4-((cis-2,6-dimethylmorpholino)methyl)styryl)-1H-indazol-6-yl)-5‘-methoxyspiro[cyclopropane-1,3’-indolin]-2-one maleic acid

(1R,2S)-(E)-2-(3-(4-((cis-2,6-dimethylmorpholino)methyl)styryl)-1H-indazol-6-yl)-5‘-methoxyspiro[cyclopropane-1,3’-indolin]-2-one fumarate

Refernces

• 1、 -. "KINASE INHIBITORS AND METHOD OF TREATING CANCER WITH SAME". Page/Page column 127-128. . Retrieved 2011/10/31.