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

Preparation of N-{4-[3-chloro-4-(3-fluoro-benzyloxy)-anilino]-quinazoline-6-yl}-acrylamide

A technology of acrylamide and benzyloxy, which is applied in the field of pharmaceutical synthesis, can solve the problems of no crystal form, low product quality, high price, etc., and achieves the effects of mild and fast reaction conditions, simplified purification method, and convenient post-processing

Active Publication Date: 2009-01-21
江苏艾力斯生物医药有限公司
View PDF6 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This reaction requires a relatively expensive condensing agent, and it takes a long time to complete the reaction. In addition, the post-treatment of this reaction is not easy, and it needs to be purified by column chromatography, which is not conducive to industrial production.
The product prepared by this process does not have a crystalline form, the product quality is not high, and needs to be further purified, which also brings inconvenience to the subsequent further research on using it as a medicine

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 of N-{4-[3-chloro-4-(3-fluoro-benzyloxy)-anilino]-quinazoline-6-yl}-acrylamide
  • Preparation of N-{4-[3-chloro-4-(3-fluoro-benzyloxy)-anilino]-quinazoline-6-yl}-acrylamide
  • Preparation of N-{4-[3-chloro-4-(3-fluoro-benzyloxy)-anilino]-quinazoline-6-yl}-acrylamide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] 3H-Quinazolin-4-one

[0024] Stir 50mL of formamide to raise the temperature to 145°C, then slowly add 60g of anthranilic acid, after the addition, keep warm until a large amount of solids are precipitated, terminate the reaction, pour the reaction solution into ice water, filter with suction, wash the filter cake with water until it is colorless, Vacuum drying gave 40 g of 3H-quinazolin-4-one with a yield of 62.6%, Mp 215°C.

Embodiment 2

[0026] 6-nitro-3H-quinazolin-4-one

[0027] Cool 60mL of concentrated sulfuric acid to 0°C, slowly add 30g of 3H-quinazolin-4-one obtained in the above step (the feeding temperature is controlled within 10°C), after the addition is complete, continue stirring for 10min, and slowly add 60mL of concentrated nitric acid (dropwise The heating temperature is controlled within 10°C), and then the temperature is slowly raised to about 98°C, and the reaction is kept for 3 hours. Cool to room temperature, pour the reaction solution into 600mL ice water, stir, a large amount of yellow solid precipitates, filter with suction, wash the filter cake with water until neutral, and dry in vacuo to give 6-nitro-3H-quinazolin-4-one 32.6 g, yield 83.2%.

[0028] 1 H-NMR (DMSO-d 6 , 400MHz): δ10.21(1H, d), 9.11(1H, s), 8.39(1H, d), 8.03(1H, d), 7.65(3H, d).

Embodiment 3

[0030] 4-Chloro-6-nitro-quinazoline

[0031]Add 30 g of 6-nitro-3H-quinazolin-4-one obtained in the previous step into 400 mL of dichloromethane, protect with argon, and cool in an ice-water bath. After adding 30mL of DMF, 60mL of oxalyl chloride was slowly added dropwise, a large amount of gas was generated. After the dropwise addition was completed, the temperature was raised to 25° C., and the temperature was kept until the liquid became clear, and the end point of the reaction was determined by TLC. Then the reaction solution was slowly poured into ice water with stirring. Stand still, separate layers, and the organic layer is sequentially washed with saturated Na 2 CO 3 solution, saturated NaCl solution, anhydrous Na 2 SO 4 Dry, filter with suction, and concentrate to dryness under reduced pressure to obtain 28.0 g of 4-chloro-6-nitro-quinazoline with a yield of 84.8%.

[0032] 1 H-NMR (DMSO-d 6 , 400MHz): δ9.18(1H, m), 8.60(1H, s), 8.39(1H, dd), 7.89(1H, dd), 7.6...

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 provides a method for making N-{4-[3-chloro-(3-fluoro-benzyloxy)- anilinothi]- quinazoline-6-group}-acrylamide (compound I). The method comprises following steps that N<4>-[3-chloro-4- (3-fluoro-benzyloxy)-anilinothi]-quinazoline-4,6-diamine is used as a raw material which reacts with a compound shown in the general formula III to obtain the compound II first, the compound II subsequently undergoes an elimination reaction under alkali condition to obtain the N-{4-[3-chloro-(3-fluoro-benzyloxy)- anilinothi]- quinazoline-6-group}- acrylamide.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular to a preparation method of N-{4-[3-chloro-4-(3-fluoro-benzyloxy)-anilino]-quinazolin-6-yl}-acrylamide. Background technique [0002] Protein tyrosine kinases (PTKs) are a class of enzymes that play an important role in normal cell growth, which can catalyze the transfer of phosphate groups from ATP to residues of protein substrates. Many epidermal growth factor receptor (EGFR) proteins function as protein tyrosine kinases, and the interaction of these receptors and growth factors is also required for the normal regulation of cell growth. However, the overexpression of EGFR, through the action of its own tyrosine kinase, will cause the excessive proliferation of cells, and eventually lead to the formation of tumors. [0003] The epidermal growth factor receptor family can be divided into EGFR (Erb-B1), Erb-B2 (HER-2 / neu), ErB-B3 and Erb-B4 according to their different structures. Thes...

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 Applications(China)
IPC IPC(8): C07D239/94
Inventor 姜勇蔡璇郭建辉
Owner 江苏艾力斯生物医药有限公司