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Method for preparing spiro2-diazido-indoline

A technology based on indole and azido, which is applied in the field of preparing spirocyclic 2-diazidoindoline, can solve the problems of harmful by-products, and achieve the effects of simple operation, easy preparation, and mild reaction conditions

Inactive Publication Date: 2016-05-11
INST OF CHEM CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Traditional methods of introducing azide compounds are Sandmeyer reactions, copper-catalyzed coupling reactions of aryl halides or aryl boronic acids with sodium azide or azidotrimethylsilane, which generate unwanted by-products

Method used

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  • Method for preparing spiro2-diazido-indoline
  • Method for preparing spiro2-diazido-indoline
  • Method for preparing spiro2-diazido-indoline

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1. Compound Preparation

[0038] 1) Follow figure 1 The synthetic route shown to prepare the indole raw material shown in I-a, the specific operation is as follows:

[0039] Add tryptamine (16.01g, 100.0mmol), THF (150.0mL) to the reactor in turn, and Et at room temperature 3 N(15.3mL,110mmol),(Boc) 2 O (24.007g, 110.0mmol), stir overnight. After rotary drying and column chromatography, the compound represented by formula 2-a is obtained.

[0040] Add the compound shown in 2-a (2.6g, 10.0mmol), dichloromethane (100.0mL) to the reactor, add DMAP (0.244g, 2.0mmol), Et 3 N (2.78 mL, 20.0 mmol) and ClCOOEt (3.78 mL, 40.0 mmol) were stirred at room temperature overnight. After spin-drying and column chromatography, the white solid product represented by formula I-a was 1.065 g, 32% yield.

[0041] The structure verification results are as follows: 1 HNMR(400MHz, CDCl 3 )δ8.23-8.09(m,1H),7.54(d,J=7.6Hz,1H),7.45(s,1H),7.34(t,J=7.6Hz,1H),7.25(t,J=7.6 Hz, 1H), 4.69 (brs, 1H),...

Embodiment 2

[0046] Example 2. Compound Preparation

[0047] 1) Follow image 3 The shown synthetic route prepares the indole raw material shown in I-b, and the specific operation is as follows:

[0048] Into the reactor was added 5-methoxytryptamine (1.14g, 6.0mmol), THF (20.0mL), at room temperature, Et 3 N(1.0mL,7.2mmol),(Boc) 2 O (1.54mL, 7.2mmol), stir overnight. After spin-drying, column chromatography obtains formula 2-b.

[0049] 2-b (1.63g, 5.6mmol), acetonitrile (17.0mL) were added to the reactor, DBU (0.852g, 5.6mmol) and compound 3 (1.02g, 7.3mmol) were added sequentially, and stirred at room temperature overnight. After rotary drying and column chromatography, 1.64 g of the indole raw material represented by formula I-b was obtained as a white solid with 81% yield.

[0050] The structure verification results are as follows: 1 HNMR(400MHz, CDCl 3 )δ8.15-7.95(m,1H),7.43(s,1H),7.02-6.91(m,2H), 4.63(brs,1H), 4.46(q,J=7.2Hz,2H), 3.87(s ,3H),3.52-3.40(m,2H),2.86(t,J=6.8Hz,2H),1.46(t,J=7....

Embodiment 3

[0055] Example 3. Compound Preparation

[0056] 1) Follow Figure 5 The synthetic route shown to prepare the indole raw material shown in I-c, the specific operation is as follows:

[0057] Add 5-chlorotryptamine hydrochloride (1.16g, 5.0mmol), THF (10.0mL) to the reactor successively, and Et at room temperature 3 N(2.1mL, 1.5mmol), (Boc) 2 O (1.26mL, 5.5mmol), stir overnight. After rotary drying and column chromatography, the compound represented by formula 2-c is obtained.

[0058] The compound shown in 2-c (1.47g, 5.0mmol), acetonitrile (15.0mL) were added to the reactor, DBU (0.761g, 5.0mmol) and 3 (0.910g, 6.5mmol) were added successively, and stirred at room temperature overnight. After rotary drying and column chromatography, a white solid was obtained, that is, 1.3715 g of the compound represented by formula I-c, 75% yield.

[0059] The structure verification results are as follows: 1 HNMR(400MHz, CDCl 3 )δ8.14-8.04 (m, 1H), 7.50 (d, J = 1.6 Hz, 1H), 7.47 (s, 1H), 7.29 (dd, ...

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Abstract

The invention provides a method for preparing a compound shown in the formula II (please see the formula in the description). The method includes the following step of making indole shown in the formula I (please see the formula in the description) react with a precursor and ceric ammonium nitrate in the inert atmosphere so that spiro2-diazido-indoline can be obtained, wherein the precursor can provide azide groups. In the formula I and the formula II, R1 is selected from at least one of hydrogen, an alkyl group of C1-C5, alkoxy of C1-C5, F, Br and Cl; R2 is an alkyl group of C1-C5; Boc represents t-butyloxycarboryl. The precursor is sodium azide or trimethylsilyl azide. The mole ratio of indole shown in the formula I to the precursor to ceric ammonium nitrate is 1:(2-4):(4-8). According to the simple method, the two azide groups are introduced to the organic molecule, and in other words, spiro2-diazido-indoline is effectively prepared under the effects of the precursor capable of providing the azide groups and ceric ammonium nitrate with indole of different structures as the raw material. The raw material is easy to prepare, the reaction condition is gentle, operation is easy and convenient, and yield can reach 45% at most.

Description

Technical field [0001] The invention belongs to the field of organic synthesis, and specifically relates to a method for preparing spirocyclic 2-diazidoindoline. Background technique [0002] Organic azide compounds are an important preparation intermediate, which can be easily converted into nitrogen-containing compounds, especially nitrogen-containing heterocycles in some drugs. Azide compounds have a wide range of applications in materials science, polymer chemistry, medicinal chemistry and biology. In addition, azide compounds have important biological activities. The traditional method of introducing azide compounds is the Sandmeyer reaction, a copper-catalyzed coupling reaction of aryl halide or aryl boronic acid with sodium azide or azidotrimethylsilane. These reactions can produce harmful by-products. Summary of the invention [0003] The purpose of the present invention is to provide a new method for preparing spirocyclic 2-diazidoindolines. [0004] The method for prepar...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D498/10
Inventor 史一安李静刘懋田华
Owner INST OF CHEM CHINESE ACAD OF SCI