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

A kind of preparation method of deuterated compound

A technology of deuterated compounds and deuterated methanol, applied in the field of preparation of deuterated compounds, can solve the problems of high price, expensive metal catalysts, long synthesis routes, etc., and achieves simple and easy operation and preparation, short deuteration time, and deuterium. high generation effect

Active Publication Date: 2020-10-09
CHIA TAI TIANQING PHARMA GRP CO LTD
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] All of the above have their own shortcomings, which limit their application.
Method 1) The synthesis route is long and cumbersome, and the deuterated raw materials are more expensive; the deuterated reducing reagent of method 2) is expensive and difficult to obtain. At present, deuterated tetrahydropotassium aluminum (LiAlD 4 ) market shortage; method 3) metal catalysts are expensive and the deuterium substitution rate is difficult to meet the requirements
At present, there are a small amount of commonly used deuterated amine compounds in the foreign market, but they are not only expensive but also limited in supply. For example, deuterated piperazine can supply up to 5 grams, and the price is as high as 500 US dollars per gram.
Expensive prices make it difficult to develop deuterated compounds and drugs

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 preparation method of deuterated compound
  • A kind of preparation method of deuterated compound
  • A kind of preparation method of deuterated compound

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0120] In another aspect, the present invention provides a method for preparing deuterated compound III, which includes reacting deuterated compound I in the presence of a reducing agent to prepare deuterated compound III;

[0121] The deuterated compound I is a compound obtained by replacing all the hydrogen atoms on the atom directly connected to N with deuterium atoms in the structural elements of the non-deuterated compound Ia, the compound containing at least one structure of the formula CNX Element, and wherein the C atom of the structural element of the formula CNX is connected to at least one deuterium atom, the N atom of the structural element of the formula CNX is not connected to a deuterium atom or a hydrogen atom, and the atom directly connected to N is not connected to Hydrogen atom connection;

[0122] The deuterated compound III is that all structural elements of the formula C-N-X of the deuterated compound I are transformed into the formula C-N-NH 2 The compound or...

Embodiment 1

[0326] Example 1: N-[D 3 ] Preparation of methylaniline (compound of formula IV-1)

[0327]

[0328] (E / Z) Preparation of N-nitroso-N-methylaniline (compound of formula II-1): NaNO 2 (7.84g, 112mmol) and water (20mL) are slowly added dropwise to the solution composed of N-methylaniline (8.0g, 74.68mmol), water (9.6mL) and acetic acid (48mL), after the addition is complete The reaction was stirred at 0°C for 2 hours. After the reaction was completed, it was extracted 4 times with dichloromethane (20 mL each time). The dichloromethane layer was washed twice with a saturated aqueous sodium chloride solution (10 mL each time). Anhydrous sodium carbonate and The aqueous magnesium sulfate was dried, filtered, and the filtrate was concentrated under reduced pressure. The concentrate was dissolved in dichloromethane and adjusted to a pH greater than 7 with saturated sodium carbonate solution. After the organic phase was dried with anhydrous magnesium sulfate, filtered, and the filtrate w...

Embodiment 2

[0334] Example 2: Two-[D 3 ] Preparation of methylamine hydrochloride (compound of formula VIII-1)

[0335]

[0336] (E / Z) Preparation of N-nitrosodimethylamine (compound of formula VI-1): Weigh the compound of formula V-1 (45g, 0.552mol) and 2mol / L HCl aqueous solution (165mL) in 500mL two In a neck flask, cool down to 0℃, and put NaNO 2 (57g, 0.826mol) dissolved in 180mL of water, added dropwise to the reaction flask at 0°C, kept at 0°C and reacted for 2 hours after the dropwise addition, stirred overnight at room temperature, and extracted 4 times with dichloromethane after the reaction was completed. The dichloromethane layer was dried by adding anhydrous sodium carbonate and anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure at not higher than 30°C to obtain a compound of formula VI-1 (29.33g, yellow-green liquid).

[0337] 1 HNMR(300MHz, CDCl 3 ): δ3.04 (s, 3H, the same isomer with the N=O group), 3.76 (ms, 3H, the reverse isomer w...

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 present invention relates to the field of chemical synthesis, and specifically to a preparation method for a deuterated compound. The preparation method comprises: converting a non-deuterated compound at least containing one structural element having a C-N-X formula into a corresponding deuterated compound in the presence of a deuterium source, wherein X indicates nitroso, nitro, hydroxy, cyan or alogen, the used deuterium source is selected from heavy water or deuterated alcohol, and the deuterium source is easy to obtain; the cost is low, the operation is simple and convenient, the preparation is easy, the deuteration time is short, the deuteration rate is high, the primary deuteration rate can be up to above 90 percent, a deuteration process has no use of high-toxicity reagent, and the preparation method is green and environment-friendly, and is particularly suitable for being applied to develop deuterated medicine.

Description

Technical field [0001] The invention relates to the field of chemical synthesis, in particular to a method for preparing a deuterated compound. Background technique [0002] There are three isotopes of hydrogen: protium ( 1 H, Hydrogen, Protium), deuterium ( 2 H, Deuterium) and tritium ( 3 H, Tritium). Where deuterium ( 2 H or D) is one of the most widely used isotopes. It is the hydrogen that exists in nature ( 1 H, a stable isotope of protium), non-radioactive, was first discovered in water by Urey in 1932. The nucleus of deuterium is composed of one neutron and one proton, while hydrogen (protium) has only one proton. The content of deuterium in nature is about 0.015%. At present, a large amount of deuterium is separated from water in the form of deuterated water, and its content can reach 99.9%. Deuterated water, also called heavy water, is currently the most economical and easily available source of deuterium. [0003] Deuterium isotopes and their deuterated compounds have ...

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): C07C243/04C07C211/48C07D295/30C07D205/04C07D213/74C07D401/04C07D215/58C07D471/04C07D217/02C07D241/54
CPCC07C211/48C07C243/04C07D205/04C07D213/74C07D215/58C07D217/02C07D241/54C07D295/30C07D401/04C07D471/04
Inventor 张寅生高勇柳英帅林志强
Owner CHIA TAI TIANQING PHARMA GRP CO LTD