Alternatived Products of [ 606143-89-9 ]
Product Details of [ 606143-89-9 ]
CAS No. : | 606143-89-9 |
MDL No. : | MFCD22124525 |
Formula : |
C17H15BrF2N4O3
|
Boiling Point : |
- |
Linear Structure Formula : | - |
InChI Key : | ACWZRVQXLIRSDF-UHFFFAOYSA-N |
M.W : |
441.23
|
Pubchem ID : | 10288191 |
Synonyms : |
MEK162;ARRY-162;Brand name: Mektovi.;ARRY438162, Binimetinib;ARRY-438162;ARRY-438162
|
Safety of [ 606143-89-9 ]
Application In Synthesis of [ 606143-89-9 ]
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
- Upstream synthesis route of [ 606143-89-9 ]
- Downstream synthetic route of [ 606143-89-9 ]
- 2
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[ 606143-48-0 ]
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[ 606143-89-9 ]
- 3
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6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid methyl ester
[ No CAS ]
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[ 606143-89-9 ]
- 4
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6-(4-bromo-2-fluoro-phenylamino)-7-fluoro-3-methyl-3 Hbenzoimidazole-5-carboxylic acid (2-vinyloxy-ethoxy)-amide
[ No CAS ]
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[ 606143-89-9 ]
Yield | Reaction Conditions | Operation in experiment |
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With hydrogenchloride; In ethanol; for 24.0h; |
Hydrochloric acid (14 mL, 1.0 M aqueous solution, 14 mmol) is added to a suspensionof the previous compound in ethanol and the reaction mixture allowed to stir for 24 hours. Thereaction mixture is concentrated to dryness by rotary evaporation and the solids partitioned between 3:1 ethyl acetate/tetrahydrofuran and saturated potassium carbonate. The aqueous phase is extracted with 3:1 ethyl acetate/tetrahydrofuran (3x), the combined organics dried (Na2SO4), and concentrated to 6-(4-bromo-2-fluoro-phenylamino)-7-fluoro-3 -methyl-3 H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide as an off-white solid. |
- 5
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6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid
[ No CAS ]
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[ 606143-89-9 ]
- 6
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[ 1604812-70-5 ]
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[ 606143-89-9 ]
Yield | Reaction Conditions | Operation in experiment |
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With phosphoric acid; water; In acetonitrile; at 20 - 53℃; for 6.25h; |
6-(4-Bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5- carboxylic acid-(2-tert-butoxyethoxy)-amide (Compound 5) monohydrate is added in 3 portions to a premixed solution of Acetonitrile and excess Phosphoric acid (85 % aqueous solution) at internal temperature 20-25 C. After stirring for about 15 minutes, the suspension is heated to internal temperature 50-53 C. The suspension is maintained at this temperature for 6 hours, cooled to internal temperature 20-25 C. The mixture is then heated to internal temperature 35-37C and diluted with Ethanol- Water (3 :1 v/v). EKNS and CEFOK are added, the reaction mixture is stirred approximately 15 minutes and filtered over a funnel coated with CEFOK. The filtrate is cooled to approximately 30C. 3 N aqueous potassium hydroxide (KappaOmicronEta) is added to the cooled filtrate over a period of 90 minutes until a pH- value of about 8.1 is reached. The suspension is heated to internal temperature 60-63 C, stirred at this temperature for a period of about 2 hours, cooled to 20-23 C over a period of about 45 minutes, filtered over a funnel, and dried at 50C pressure <100 mbar over a period of about 17 hours, providing 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H- benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide (Compound A) as a white powder. |
- 7
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[ 1604812-73-8 ]
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[ 606143-89-9 ]
- 8
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[ 918321-20-7 ]
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[ 606143-89-9 ]
- 9
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[ 105931-73-5 ]
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[ 606143-89-9 ]
- 10
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[ 1604812-72-7 ]
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[ 606143-89-9 ]
- 11
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[ 606143-89-9 ]
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[ 1211441-98-3 ]
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C23H30N8O*C17H15BrF2N4O3
[ No CAS ]
Yield | Reaction Conditions | Operation in experiment |
|
In water; acetonitrile; at 50℃; |
26.6 mg of MEK 162 and 4 mL of acetonitrile / water (v: v = 19: 1) were stirred at 50 C for 30 minutes, 16.0 mg of LEE011 was added, stirring was continued overnight and the temperature was slowly cooled to 20 C and the solid was collected. |
- 12
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[ 606143-89-9 ]
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[ 77-92-9 ]
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[ 2469765-25-9 ]
Yield | Reaction Conditions | Operation in experiment |
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In methanol for 2h; |
6 Example 6 - Binimetinib citric acid molecular complex
Binimetinib (ca. 30 mg) and 1 .0 eq. (ca. 13 mg) of citric acid were dispensed into an HPLC vial and two stainless steel grinding balls (3 mm diameter) added. Solvent was added (MeOH, 10 mI) and the sample was subjected to grinding on a Fritsch planetary mill (500 rpm, 2 hour duration). The solid obtained was analysed by XRPD and was identified as binimetinib citric acid molecular complex. |
- 13
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[ 284030-58-6 ]
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[ 606143-89-9 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 7 steps
1: 5,5-dimethyl-1,3-cyclohexadiene / 150 - 155 °C
2: palladium on activated charcoal; hydrogen / methanol; tetrahydrofuran / 50 - 55 °C
3: toluene-4-sulfonic acid / water; acetonitrile / 60 - 65 °C
4: toluene-4-sulfonic acid; N-Bromosuccinimide / methanol; tetrahydrofuran / -78 - 20 °C / Inert atmosphere
5: sodium hydroxide; water / tetrahydrofuran / 20 °C
6: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / N,N-dimethyl-formamide / 20 °C
7: water; hydrogenchloride; ethanol / 24 h |
|
- 14
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[ 348-54-9 ]
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[ 606143-89-9 ]
Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 7 steps
1: 5,5-dimethyl-1,3-cyclohexadiene / 150 - 155 °C
2: palladium on activated charcoal; hydrogen / methanol; tetrahydrofuran / 50 - 55 °C
3: toluene-4-sulfonic acid / water; acetonitrile / 60 - 65 °C
4: toluene-4-sulfonic acid; N-Bromosuccinimide / methanol; tetrahydrofuran / -78 - 20 °C / Inert atmosphere
5: sodium hydroxide; water / tetrahydrofuran / 20 °C
6: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / N,N-dimethyl-formamide / 20 °C
7: water; hydrogenchloride; ethanol / 24 h |
|
- 15
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[ 2509103-99-3 ]
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[ 606143-89-9 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 3 steps
1: sodium hydroxide; water / tetrahydrofuran / 20 °C
2: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / N,N-dimethyl-formamide / 20 °C
3: water; hydrogenchloride; ethanol / 24 h |
|
- 16
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[ 606143-94-6 ]
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[ 606143-89-9 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 6 steps
1: palladium on activated charcoal; hydrogen / methanol; tetrahydrofuran / 50 - 55 °C
2: toluene-4-sulfonic acid / water; acetonitrile / 60 - 65 °C
3: toluene-4-sulfonic acid; N-Bromosuccinimide / methanol; tetrahydrofuran / -78 - 20 °C / Inert atmosphere
4: sodium hydroxide; water / tetrahydrofuran / 20 °C
5: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / N,N-dimethyl-formamide / 20 °C
6: water; hydrogenchloride; ethanol / 24 h |
|
- 17
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[ 1415560-46-1 ]
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[ 606143-89-9 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 5 steps
1: toluene-4-sulfonic acid / water; acetonitrile / 60 - 65 °C
2: toluene-4-sulfonic acid; N-Bromosuccinimide / methanol; tetrahydrofuran / -78 - 20 °C / Inert atmosphere
3: sodium hydroxide; water / tetrahydrofuran / 20 °C
4: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / N,N-dimethyl-formamide / 20 °C
5: water; hydrogenchloride; ethanol / 24 h |
|
- 18
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[ 1415559-89-5 ]
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[ 606143-89-9 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 4 steps
1: toluene-4-sulfonic acid; N-Bromosuccinimide / methanol; tetrahydrofuran / -78 - 20 °C / Inert atmosphere
2: sodium hydroxide; water / tetrahydrofuran / 20 °C
3: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / N,N-dimethyl-formamide / 20 °C
4: water; hydrogenchloride; ethanol / 24 h |
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- 19
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[ 2649854-86-2 ]
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[ 606143-89-9 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 3 steps
1.1: potassium carbonate / N,N-dimethyl-formamide / 20 °C
1.2: 20 °C
1.3: Inert atmosphere
2.1: N-Bromosuccinimide; toluene-4-sulfonic acid / tetrahydrofuran; methanol / -77 - 20 °C / Inert atmosphere
3.1: water; phosphoric acid / acetonitrile / 50 - 55 °C |
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- 20
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[ 2649854-88-4 ]
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[ 606143-89-9 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 2 steps
1: N-Bromosuccinimide; toluene-4-sulfonic acid / tetrahydrofuran; methanol / -77 - 20 °C / Inert atmosphere
2: water; phosphoric acid / acetonitrile / 50 - 55 °C |
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- 21
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[ 2649854-82-8 ]
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[ 606143-89-9 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 5 steps
1: potassium carbonate / N,N-dimethyl-formamide / 20 °C
2: sodium hydroxide; water / tetrahydrofuran / 20 °C
3: benzotriazol-1-ol; triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 20 °C / Inert atmosphere
4: 5,5-dimethyl-1,3-cyclohexadiene / 125 - 140 °C
5: water; phosphoric acid / acetonitrile / 50 - 55 °C |
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- 22
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[ 2649854-83-9 ]
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[ 606143-89-9 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 4 steps
1: sodium hydroxide; water / tetrahydrofuran / 20 °C
2: benzotriazol-1-ol; triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 20 °C / Inert atmosphere
3: 5,5-dimethyl-1,3-cyclohexadiene / 125 - 140 °C
4: water; phosphoric acid / acetonitrile / 50 - 55 °C |
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- 23
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[ 2649854-84-0 ]
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[ 606143-89-9 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 3 steps
1: benzotriazol-1-ol; triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 20 °C / Inert atmosphere
2: 5,5-dimethyl-1,3-cyclohexadiene / 125 - 140 °C
3: water; phosphoric acid / acetonitrile / 50 - 55 °C |
|
- 24
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[ 606143-89-9 ]
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[ 1415564-99-6 ]
Yield | Reaction Conditions | Operation in experiment |
69.51% |
With hydrogenchloride In water at 85℃; |
88 Synthesis ooff 5-((4-bromo-2-fluorophenyl)amino)-4-fluoro-l -methyl- 1H- benzo[d]imidazole-6-carboxylic acid
Binimetinib (3.92 g, 8.88 mmol) in aqueous 1 M hydrogen chloride (47.2 mL, 1.72 g, 47.19 mmol) was heated to 85 °C for 48 h. The reaction was cooled to room temperature and neutralized with aqueous 1 M NaOH to pH 6. The resulting precipitate was collected by filtration and lyophilized to provide 5-((4-bromo-2-fluorophenyl)amino)-4-fluoro-l-methyl-lH- benzo[d]imidazole-6-carboxylic acid (2.36 g, 69.51%) as a white solid. LCMS: CisHioBrFzNsCh requires: 381.0, found: m/z = 382.2 [M+H]+. |
69.51% |
With hydrogenchloride In water at 85℃; |
88 Synthesis ooff 5-((4-bromo-2-fluorophenyl)amino)-4-fluoro-l -methyl- 1H- benzo[d]imidazole-6-carboxylic acid
Binimetinib (3.92 g, 8.88 mmol) in aqueous 1 M hydrogen chloride (47.2 mL, 1.72 g, 47.19 mmol) was heated to 85 °C for 48 h. The reaction was cooled to room temperature and neutralized with aqueous 1 M NaOH to pH 6. The resulting precipitate was collected by filtration and lyophilized to provide 5-((4-bromo-2-fluorophenyl)amino)-4-fluoro-l-methyl-lH- benzo[d]imidazole-6-carboxylic acid (2.36 g, 69.51%) as a white solid. LCMS: CisHioBrFzNsCh requires: 381.0, found: m/z = 382.2 [M+H]+. |
- 25
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[ 606143-89-9 ]
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[ 2865157-15-7 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 2 steps
1: hydrogenchloride / water / 48 h / 85 °C
2: triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C |
|
- 26
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[ 606143-89-9 ]
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[ 2939086-75-4 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 3 steps
1: hydrogenchloride / water / 48 h / 85 °C
2: triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C
3: dichloromethane / 3 h / 20 °C |
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- 27
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[ 606143-89-9 ]
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[ 2865157-17-9 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 2 steps
1: hydrogenchloride / water / 48 h / 85 °C
2: triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C |
|
- 28
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[ 606143-89-9 ]
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[ 2939086-76-5 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 3 steps
1: hydrogenchloride / water / 48 h / 85 °C
2: triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C
3: 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran / 2 h / 20 °C |
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- 29
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[ 197520-71-1 ]
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[ 606143-89-9 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 6 steps
1.1: ammonia / water / 2.5 h / 0 - 30 °C
2.1: N-ethyl-N,N-diisopropylamine / 9.16 h / 25 - 110 °C
3.1: hydrogen / methanol; tetrahydrofuran / 13 h / 25 - 70 °C / Autoclave
4.1: toluene-4-sulfonic acid / water; acetonitrile / 5 min / 25 - 30 °C
4.2: 210 min / 25 - 65 °C
5.1: benzotriazol-1-ol / N,N-dimethyl-formamide / 20 min / 25 - 30 °C
5.2: 10 min / 25 - 30 °C
5.3: 5 h / 25 - 30 °C
6.1: trifluoroacetic acid / dichloromethane / 5 h / 5 - 30 °C |
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- 30
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[ 284030-57-5 ]
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[ 606143-89-9 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 5 steps
1.1: N-ethyl-N,N-diisopropylamine / 9.16 h / 25 - 110 °C
2.1: hydrogen / methanol; tetrahydrofuran / 13 h / 25 - 70 °C / Autoclave
3.1: toluene-4-sulfonic acid / water; acetonitrile / 5 min / 25 - 30 °C
3.2: 210 min / 25 - 65 °C
4.1: benzotriazol-1-ol / N,N-dimethyl-formamide / 20 min / 25 - 30 °C
4.2: 10 min / 25 - 30 °C
4.3: 5 h / 25 - 30 °C
5.1: trifluoroacetic acid / dichloromethane / 5 h / 5 - 30 °C |
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- 31
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[ 1908446-79-6 ]
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[ 606143-89-9 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 4 steps
1.1: hydrogen / methanol; tetrahydrofuran / 13 h / 25 - 70 °C / Autoclave
2.1: toluene-4-sulfonic acid / water; acetonitrile / 5 min / 25 - 30 °C
2.2: 210 min / 25 - 65 °C
3.1: benzotriazol-1-ol / N,N-dimethyl-formamide / 20 min / 25 - 30 °C
3.2: 10 min / 25 - 30 °C
3.3: 5 h / 25 - 30 °C
4.1: trifluoroacetic acid / dichloromethane / 5 h / 5 - 30 °C |
|
- 32
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[ 1908446-77-4 ]
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[ 606143-89-9 ]
Yield | Reaction Conditions | Operation in experiment |
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Multi-step reaction with 3 steps
1.1: toluene-4-sulfonic acid / water; acetonitrile / 5 min / 25 - 30 °C
1.2: 210 min / 25 - 65 °C
2.1: benzotriazol-1-ol / N,N-dimethyl-formamide / 20 min / 25 - 30 °C
2.2: 10 min / 25 - 30 °C
2.3: 5 h / 25 - 30 °C
3.1: trifluoroacetic acid / dichloromethane / 5 h / 5 - 30 °C |
|
- 33
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[ 2952778-64-0 ]
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[ 606143-89-9 ]
Yield | Reaction Conditions | Operation in experiment |
9 g |
With trifluoroacetic acid In dichloromethane at 5 - 30℃; |
8 Example-8: Preparation of Binimetinib of Formula-1.
Dichloromethane (150.0 ml) was added to compound of formula-2 (15.0 gm) at 25-30°C and stirred for 5 minutes. Cooled the mixture to 5-10°C and stirred for 20 minutes. Trifluoroacetic acid (75.0 ml) was added to the mixture at 5-10°C and stirred for 1 hour. Raised the temperature of the mixture to 25-30°C and stirred for 4 hours. Mixture was added to precooled sodium carbonate solution at 5-10°C and stirred for 1 hour. Raised the temperature of the mixture to 25-30°C and stirred for 1 hour. Filtered the solid and washed with water. Water (300.0 ml) was added to the obtained compound at 25-30°C and stirred for 10 minutes. Heated the mixture to 55-60°C and stirred for 90 minutes. Filtered the solid, washed with water and dried. Acetonitrile (220.0 ml) was added to the obtained compound at 25-30°C and stirred for 5 minutes. Heated the mixture to 80-85°C and stirred for 1 hour. Cooled the mixture to 25-30°C and stirred for 2 hours. Filtered the solid and washed with acetonitrile. Acetonitrile (200.0 ml) was added to the obtained compound at 25-30°C and stirred for 5 minutes. Heated the mixture to 80-85°C and stirred for 1 hour. Cooled the mixture to 25-30°C and stirred for 2 hours. Filtered the solid, washed with acetonitrile and dried to get the title compound.Yield: 9.0 gm; Purity by HPLC: 99.59% |