Unlock instant, AI-driven research and patent intelligence for your innovation.

A kind of chemical synthesis method of carbitinib

A technology of chemical synthesis and carbitinib, applied in organic chemistry methods, organic chemistry, etc., can solve the problems of long synthesis steps, difficult separation, environmental pollution, etc., and achieve mild synthesis conditions, easy control of reactions, and safety high effect

Active Publication Date: 2017-12-26
JINING MEDICAL UNIV
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] To sum up, there have been many research reports on the synthesis methods of carbitinib, but there are many defects, such as rare raw materials, long synthesis steps, low yield, difficult separation, serious environmental pollution, etc.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A kind of chemical synthesis method of carbitinib
  • A kind of chemical synthesis method of carbitinib
  • A kind of chemical synthesis method of carbitinib

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Synthesis of Example 1 Compound 2

[0045]

[0046] Compound 1 (26.6g, 0.1mol, 1.0eq) was dissolved in DMF (200ml), stirred to dissolve, and 2-fluoro-4-iodoaniline (26.07g, 0.11mol, 1.1eq) was added, and placed in 0 o Under the condition of C, N, N-diisopropylethylamine (69.3ml, 0.5mol, 5.0eq) was added dropwise under stirring. After the addition, the reaction solution was placed in 60 o Under the condition of C, react for 6h, add 1000ml of 0.5mol / L HCl solution to the reaction solution, stir for 10min, then add 500ml of ethyl acetate to the reaction solution, extract, collect the organic layer, and extract the aqueous layer with ethyl acetate (500ml×3 ), combined organic layers, dried over anhydrous magnesium sulfate for 2h, filtered, and removed ethyl acetate by distillation under reduced pressure to obtain a yellow oily liquid, which was purified by column chromatography (200-300 mesh silica gel was the stationary phase, dichloromethane : Methanol=4:1 is the elue...

Embodiment 2

[0050] Synthesis of Example 2 Compound 3

[0051]

[0052] A glass autoclave was charged with 10% Pd / C (11.7g, 4.4mmol, 0.05eq, 60.2%ww water, 10%ww palladium on carbon) and compound 2 (42.7g, 0.088mol, 1.0eq) under argon. Dissolve in 200ml absolute ethanol, room temperature H 2 Pressurize (20~60psi) to react overnight, remove 10% Pd / C by diatomaceous earth filtration, collect the filtrate, and remove the solvent under reduced pressure to obtain 34.20 g of compound 3 (yellow oil) with a yield of 98.8%. The magnetic resonance spectrum and mass spectrometry data of compound 3 are as follows:

[0053] 1 H NMR (500Hz, CDCl 3 ): δ7.704-7.695(m, 1H), 7.198-7.185(m, 1H), 7.064-7.054(m, 1H), 6.815-6.802(m, 1H), 6.556-6.545(m, 1H).

[0054] 13 C NMR (500Hz, CDCl 3 ): δ 169.743, 160.221, 154.859, 147.094, 138.428, 136.272, 130.569, 127.149, 125.144, 123.296, 112.885, 107.493, 94.195.

[0055] MS(EI): 393.98(MH + ).

Embodiment 3

[0056] Synthesis of Example 3 Compound 4

[0057]

[0058] Weigh compound 3 (33.07g, 0.08mmol, 1.0eq), 3-oxoazetidine hydrochloride (10.36g, 0.088mmol, 1.1eq), EDCI (18.41g, 0.096mol, 1.2eq) In DCM (300ml), then add DMAP (0.49g, 4mmol, 0.05eq), stir the reaction at room temperature for 9h, add 200ml of water to quench the reaction, extract the aqueous layer with DCM (200ml×2), collect the organic layer, and wash with saturated brine Then dried over anhydrous sodium sulfate. Filtration, the filtrate was concentrated to obtain a yellow solid, which was dissolved in 20ml of dichloromethane and dropped into 300ml of n-heptane. After the dropwise addition, stirred for 2h, a solid precipitated, collected by filtration, and dried to obtain compound 4 (white Solid matter) 32.85g, yield 91.9%. The magnetic resonance spectrum and mass spectrometry data of compound 4 are as follows:

[0059] 1 H NMR (500Hz, CDCl 3 ):δ 7.628-7.614(m, 1H), 7.245-7.231(m, 1H), 7.151-7.139(m, 1H), 6....

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention belongs to the field of chemical synthesis and specifically relates to a preparation method for cobimetinib. The method comprises the following steps: by taking 2,3,4-benzyl trifluorobenzoate as an initial raw material, performing substitution reaction, deprotection reaction, amidation reaction and catalytic addition reaction, thereby obtaining the cobimetinib. The method provided by the invention has the advantages of easily-obtained and low-cost raw materials, short process flow, easiness in operation of industrial reaction, high yield, environmental protection and suitability for industrial batch production.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and in particular relates to a chemical synthesis method of an antineoplastic drug carbitinib. Background technique [0002] Melanoma, also known as malignant melanoma, is a type of malignant tumor derived from melanocytes. It is commonly found in the skin, and also in mucous membranes, eye choroid and other parts. Prolonged exposure of the human body to ultraviolet light is the main cause of melanoma formation. Although melanoma accounts for only 5% of all skin cancers, it has grown rapidly in recent decades. Melanoma is the most malignant type of skin tumor, prone to distant metastasis, and has a high mortality rate. [0003] The treatment methods for malignant melanoma mainly include surgery, chemotherapy, immunotherapy and targeted therapy. Malignant melanoma has a high degree of malignancy and is easy to transfer. Once it is diagnosed, it should be surgically removed as soon as possible....

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07D401/04
CPCC07B2200/07C07D401/04
Inventor 石茂健周金辉徐志强管华上官国强
Owner JINING MEDICAL UNIV