A kind of synthetic method of n-deuteromethylindole compound
A deuterated methyl indole and synthetic method technology, applied in the field of synthesis of deuterium-containing compounds, can solve the problems of unfavorable industrial scale-up production, difficult experimental operation, high price, etc., and achieve the benefits of industrial scale-up production and low operation difficulty , easy storage effect
Active Publication Date: 2022-01-25
TETRANOV PHARMA CO LTD
View PDF0 Cites 0 Cited by
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
However, the deuterated methyl iodide reagent has the following disadvantages: it is expensive, highly toxic, volatile, and requires low-temperature storage, which causes difficulties in experimental operations and is not conducive to industrial scale-up production.
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 moreImage
Smart Image Click on the blue labels to locate them in the text.
Smart ImageViewing Examples
Examples
Experimental program
Comparison scheme
Effect test
Embodiment 1
[0036]
[0037] Preparation of target compound Ⅲ-1:
[0038] 65.3g of indole was dissolved in 500mL of acetonitrile, NaOH 67.2g was added at room temperature, and then 116g of formula II-1 (TsOCD 3 ) in 500 mL of acetonitrile, stirred overnight at room temperature. After the LC monitors that the reaction is complete, add 1000 mL of a mixed solvent with a volume ratio of petroleum ether / ethyl acetate = 10 / 1, filter, and dissolve the filtrate with 1000 mL of a mixed solvent with a volume ratio of petroleum ether / ethyl acetate = 5 / 1. After washing with water, the organic phase was dried and then concentrated to obtain the compound N-deuteromethylindole with a purity of >95% and a deuteration rate of >99.5%. The NMR data are as follows:
[0039] 1 H NMR (400MHz, CDCl 3 ,ppm):δ=7.62(d,J=9.2Hz,1H),7.31(dd,J=8.2Hz,0.8Hz1H),7.23-7.19(m,1H),7.12-7.08(m,1H),7.02 (d, J=3.1 Hz, 1H), 6.48 (dd, J=3.1 Hz, 0.7 Hz, 1H).
[0040] Referring to the above examples, a series of compounds 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
Login to View More Abstract
The invention belongs to the technical field of synthesis of deuterium-containing compounds, and specifically discloses a synthesis method of N-deuteromethylindole compounds. The synthesis method of the N-deuterated methyl indole compound is: the compound shown in formula I and the compound shown in formula II are in an organic solvent, under the condition of the presence of alkali, stirring and reacting to obtain the N-deuterated compound shown in formula III. Methylindole compounds. The method for synthesizing N-deuteromethylindole compounds provided by the invention has mild reaction conditions, low operation difficulty and easy industrial scale-up production. The deuterated methanol sulfonate represented by the deuterated reagent formula II has the characteristics of low cost, low toxicity and easy storage. Therefore, the synthesis method of the present invention has low cost and simple operation, which is beneficial to industrial scale-up production. The method for synthesizing N-deuteromethylindole compounds provided by the invention has complete reaction of reactants, few side reactions, high product yield and simple post-treatment.
Description
technical field [0001] The invention relates to the technical field of synthesis of deuterium-containing compounds, in particular to a synthesis method of N-deuteromethylindole compounds. Background technique [0002] Deuterium, a stable isotope of hydrogen (H), generally has very low toxicity. Since the deuterium atom is twice as heavy as the hydrogen atom, the carbon-deuterium bond (C—D) has a lower vibration zero point energy than the carbon-hydrogen bond (C—H), which means that the carbon-deuterium bond is more stable than the carbon-hydrogen bond. The isotope effect on order kinetics is approximately 9-fold at 37°C (kH / kD=9). Deuterated drugs replace part of the hydrogen atoms in the drug molecule with deuterium atoms, and the activity of the drug molecule remains basically unchanged. At the same time, the kinetic isotope effect can be used to block the metabolic site and prolong the half-life of the drug, thereby reducing the therapeutic dose. Improve the pharmacokin...
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
Login to View More Patent Type & Authority Patents(China)
IPC IPC(8): C07D209/08
CPCC07D209/08C07B2200/05
Inventor 吴豫生耿阳牛成山梁阿朋
Owner TETRANOV PHARMA CO LTD