Novel urea type compound preparation method

A compound and new method technology, applied in the field of preparation of urea compounds, can solve the problems of easy oxidation, difficult preparation, high toxicity, etc., and achieve the effect of mild reaction conditions, easy separation and purification, and stable oxidation

Inactive Publication Date: 2015-04-22
CHENGDU LIKAI CHIRAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these methods have some disadvantages such as: (1) some amine compounds are not stable and easy to be oxidized; (2) phosgene and its substitutes are too toxic and cumbersome to operate, and their activity is too high to easily cause s

Method used

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  • Novel urea type compound preparation method
  • Novel urea type compound preparation method
  • Novel urea type compound preparation method

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0023] Example 1: Synthesis of compound ( I - a )

[0024]

[0025] Add 3-bromo-3-benzylindolin-2-one ( II ) (0.1 mmol, 30.2 mg), O -Tosyl- N -Benoxycarbonyl hydroxylamine ( III ) (0.15 mmol, 48.2 mg), CsCO 3 (0.2 mmol, 38.6 mg), then 2 ml of dichloromethane was added, and the mixture was stirred at room temperature for 14 h. Then p-toluenesulfonic acid (0.25 mmol, 43.1 mg) was added, and the reaction mixture was stirred at room temperature for 8 h. After the reaction is complete, the solvent is evaporated under reduced pressure to obtain a crude product. The crude product is separated and purified by column chromatography to obtain the compound I - a , White solid, the yield is 94%.

[0026] Compound obtained I-a The hydrogen spectrum, carbon spectrum and mass spectrum data of is as follows:

[0027] 1 H NMR (DMSO-d 6 , 300 MHz), δ (ppm): 4.42 (s, 2H), 5.20 (s, 2H), 7.19-7.43 (m, 11H), 7.55-7.61 (m, 1H), 8.17-8.20 (m, 1H), 8.35 (d, J = 7.8 Hz, 1H), 10.53 (s, 1H), 11.88 (s, 1...

Example Embodiment

[0028] Example 2: Synthesis of compound ( I - b )

[0029]

[0030] Add 3-bromo-3-(2-methylbenzyl)indolin-2-one ( II ) (0.1 mmol, 31.6 mg), O -Tosyl- N -Benoxycarbonyl hydroxylamine ( III ) (0.15 mmol, 48.2 mg), K 2 CO 3 (0.2 mmol, 27.6 mg), then 2 ml of acetonitrile was added, and the mixture was stirred at room temperature for 16 h. Then p-toluenesulfonic acid (0.25 mmol, 43.1 mg) was added, and the reaction mixture was stirred at room temperature for 8 h. After the reaction is complete, acetonitrile is evaporated under reduced pressure to obtain a crude product. The crude product is separated and purified by column chromatography to obtain the compound I - b (White solid, yield 99%).

[0031] Compound obtained I-b The hydrogen spectrum, carbon spectrum and mass spectrum data of is as follows:

[0032] 1 H NMR (DMSO-d 6 , 300 MHz), δ (ppm): 2.15 (s, 3H), 4.47 (s, 2H), 5.17 (s, 2H), 7.15-7.18 (m, 4H), 7.24 (t, J = 7.8 Hz, 1H), 7.34-7.39 (m, 5H), 7.57-7.63 (m, 1H), 8.21-8.24 ...

Example Embodiment

[0033] Example 3: Synthesis of compound ( I - c )

[0034]

[0035] Add 3-bromo-3-(3-methylbenzyl)indolin-2-one ( II ) (0.1 mmol, 31.6 mg), O -Tosyl- N -Benoxycarbonyl hydroxylamine ( III ) (0.15 mmol, 48.2 mg), Et 3 N (0.4 mmol, 40.4 mg), then 2 ml of toluene was added, and the mixture was stirred at room temperature for 30 h. Then p-toluenesulfonic acid (0.25 mmol, 43.1 mg) was added, and the reaction mixture was stirred at room temperature for 8 h. After the reaction is complete, the toluene is evaporated under reduced pressure to obtain a crude product. The crude product is separated and purified by column chromatography to obtain the compound I - c (White solid, 92% yield).

[0036] Compound obtained I - c The hydrogen spectrum, carbon spectrum and mass spectrum data of is as follows:

[0037] 1 H NMR (DMSO-d 6 , 300 MHz), δ (ppm): 2.27 (s, 3H), 4.37 (s, 2H), 5.20 (s, 2H), 7.04-7.06 (m, 3H), 7.18-7.23 (m, 2H), 7.34-7.43 (m, 5H) ), 7.55-7.61 (m, 1H), 8.16-8.19 (m, 1H), 8.3...

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Abstract

The invention discloses a novel urea type compound preparation method, and belongs to the technical field of organic synthesis. 3-halogenate oxidation indole as shown in a structural formula II reacts with O-tosyl-N-carbobenzoxy-hydroxylamine as shown in a structural formula III for 10 to 30 hours at 0 DEG C to 100 DEG C in an organic solvent under the existence of alkali, then organic acid is added, the reaction is conducted continuously, after complete reaction is finished, the solvent is dried by distillation, separated and purified, and a product is obtained. By means of the method, utilization of poisonous phosgene and substitutes of the poisonous phosgene is avoided, and raw materials and intermediate products are stable and not prone to being oxidized; the intermediate products and end-products are easy to separate and purify; the operation is simple, the reaction condition is moderate, the reaction yield is high, and the yield can reach 92%.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a new method for preparing urea compounds. Background technique [0002] Derivatives of urea widely exist in nature and are widely used in the fields of medicine, agriculture, industry and light industry. For example: the compound Diuron (A) is used as a herbicide in agriculture, the urea compound (B) with a morpholine ring structure can be used to treat chronic myelogenous leukemia, and the substituted urea compound (C) has been proved is an effective HIV-1 protease inhibitor, and compound (D) is an inhibitor of tyrosine kinase receptor (RTK). Urea compounds can also be used as catalysts to catalyze organic reactions, and some urea compounds are also important intermediates in organic synthesis. Therefore, the development of new methods for synthesizing urea compounds will bring many conveniences to the fields of medicine, agriculture and industry. [0003] [0004] So fa...

Claims

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Application Information

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IPC IPC(8): C07C273/18C07C275/60
Inventor 袁伟成左健周鸣强徐小英张晓梅
Owner CHENGDU LIKAI CHIRAL TECH
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