Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Preparation method of midbody for preparing pomalidomide

A technology for pomalidomide and intermediates, applied in the field of preparation of pomalidomide intermediates, can solve the problems of unexplained compound synthesis methods, reports, and no synthetic methods, etc., and achieve simple post-processing, easy-to-obtain raw materials, and easy reaction The effect of fewer steps

Active Publication Date: 2014-05-14
SHANGHAI INST OF PHARMA IND +1
View PDF3 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The 3-amino-[(2,6-dioxopiperidin-3-yl)carbamoyl]benzoic acid and its ester compounds have been reported in patent WO2008 / 007979A1, but this document does not describe specific compounds synthetic method, and no other literature has reported its synthetic method

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
  • Preparation method of midbody for preparing pomalidomide
  • Preparation method of midbody for preparing pomalidomide
  • Preparation method of midbody for preparing pomalidomide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] The preparation of compound III-1, wherein R is H;

[0029] 3-Nitrophthalic anhydride (I, 44.0g, 0.23mol), 3-amino-2,6-piperidinedione hydrochloride (II, 37.9g, 0.23mol), dissolved in 600mL tetrahydrofuran (THF ), then slowly add triethylamine (23.27 g, 0.23mol) dropwise to the system, and control the temperature of the system 1 H-NMR (DMSO-D6) δ: 1.88 (-*CHC H a h b CH c h d -, 1H, m), 2.21 (-*CHCH a h b C H c h d -, 1H, m), 2.53 (-*CHCH a H b CH c h d -, 1H, m), 2.72 (-*CHCH a h b CH c H d -, 1H, m), 4.74 (-* CH CH a h b CH c h d -, 1H, m), 7.76 (-ArH, 1H, t), 8.16 (-ArH, 1H, d), 8.18 (-ArH, 1H, d), 8.99 (-COOH, 1H, d), 10.85 (- CO-NH-, 1H, s), 13.60 (-CO-NH-CO-, 1H, s); ESI-MS(m / z)=322.03[M+H] + .

Embodiment 2

[0031] Compounds III-2, III-3 and III-4 are prepared from compound III-1.

[0032] Preparation of compound Ⅲ-2: wherein: R is CH 3

[0033] Compound Ⅲ-1 (32.16g, 0.10mol), methanol (3.84g, 0.12mol), dissolved in 100mL of dichloromethane, cooled in an ice bath, slowly added thionyl chloride (11.75g, 0.12mol) dropwise to the system , control the temperature of the system <5°C during the dropwise addition. After the dropwise addition is completed, raise the temperature to room temperature and react for 3.0 hours. After the reaction is complete as detected by TLC, concentrate, and add saturated sodium bicarbonate solution to the residue. Solids are precipitated, and filtered. The target compound III-2 was obtained, 30.83 g, 92%.

[0034] Preparation of compound Ⅲ-3: wherein, R is C 2 h 5

[0035] Compound Ⅲ-1 (32.16g, 0.10mol), ethanol (5.52g, 0.12mol), dissolved in 100mL of dichloromethane, cooled in an ice bath, slowly added thionyl chloride (11.75g, 0.12mol) dropwise to th...

Embodiment 3

[0039] Preparation of compound Ⅳ-1

[0040] Compound Ⅲ-1 (32.10g, 0.10mol), 10%Pd / C (50%, 16.05g) and toluene (6.42L) were added to the hydrogenation kettle, filled with a pressure of 0.1MPa, and reacted at 100°C. After the reaction was detected by TLC, it was filtered, washed with methanol (20 mL×3), the filtrate was concentrated, and dried in vacuo to obtain 27.65 g of compound IV, with a yield of 95.0%. 1 H-NMR (DMSO-D 6 )δ: 1.89 (-*CHC Ha h b CH c h d -, 1H, m), 2.16 (-*CHCH a h b C H c h d -, 1H, m), 2.51 (-*CHCH a H b CH c h d -, 1H, m), 2.78 (-*CHCH a h b CH c H d -, 1H, m), 4.65 (-* CH CH a h b CH c h d -, 1H, m), 5.51 (-NH 2 , 2H, s), 6.86 (-ArH, 1H, t), 7.02 (-ArH, 1H, t), 7.13 (-ArH, 1H, d), 8.61 (-COOH, 1H, d), 10.92 (-CO -NH-, 1H, s), 13.62 (-CO-NH-CO-, 1H, s); ESI-MS(m / z)=292.09[M+H] + .

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 discloses a preparation method of a midbody for preparing anti-multiple myeloma pomalidomide. The preparation method comprises the following steps: dissolving a compound as shown in a formula III in a solvent, reducing by using hydrogen in the existence of a palladium carbon catalyst, and then collecting a compound as shown in a formula IV from a reaction product, the compound as shown in the formula IV is the midbody, namely 3-amion-[(2,6-dioxo-3-piperidyl) carbamoyl group] benzoic acid and esters thereof for preparing the pomalidomide. The preparation method has the advantages that reaction steps are few, conditions are mild, the aftertreatment is simple, the yield is high, the preparation method is suitable for large-scale industrial production, and the reaction formula is as shown in descriptions.

Description

technical field [0001] The invention relates to a preparation method for preparing an intermediate of anti-multiple myeloma drug pomalidomide, in particular to 3-amino-[(2,6-dioxo-3-piperidinyl)carbamoyl]benzoic acid and methods for preparing esters thereof. Background technique [0002] Multiple myeloma (MM) is a malignant plasma cell disease, and its tumor cells originate from plasma cells in the bone marrow, and plasma cells are cells that develop into the final functional stage of B lymphocytes, and are currently classified as B-cell lymphocytes by WHO. A type of tumor called plasma cell myeloma / plasma cell tumor. It is characterized by abnormal proliferation of bone marrow plasma cells with overproduction of monoclonal immunoglobulins or light chains (M protein), and in rare cases can be non-secretory MM that does not produce M protein. Multiple myeloma is often accompanied by multiple osteolytic lesions, hypercalcemia, anemia, and kidney damage. Due to the suppressi...

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
IPC IPC(8): C07D211/88
CPCC07D211/88
Inventor 李建其黄道伟刘育周爱南王慧慧
Owner SHANGHAI INST OF PHARMA IND
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com