Preparation method of metaiodobenzylguanidine (MIBG) sulphate

The technology of m-iodobenzylguanidine sulfate and m-iodobenzyl bromide is applied in the field of preparation of labeling precursor m-iodobenzylguanidine sulfate, and can solve the problem that the health of production personnel is greatly affected, the residual highly toxic substances in the final product are unfavorable, and the Large-scale product preparation and other problems, to achieve the effect of reducing the risk of highly toxic substance residues, simple production operation, and easy large-scale preparation

Inactive Publication Date: 2015-04-08
BEIJING ZHIBO BIO MEDICAL TECH +1
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

The synthesis cost of the above-mentioned carrier-labeled precursor MIBG sulfate is relatively high, and highly toxic reagents such as nitrile amines are used in the synthesis process, which has a greater impact on the health of production personnel, more serious environmental pollution, and has caused serious damage to the final product. Risk of residual toxic substances, therefore not suitable for pharmaceutical production mode
In addition, the separation of products in the above methods all adopts the method of silica gel column separation, which is not conducive to the preparation of large-scale products and has high technical requirements for production personnel, which is not conducive to saving costs.

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  • Preparation method of metaiodobenzylguanidine (MIBG) sulphate
  • Preparation method of metaiodobenzylguanidine (MIBG) sulphate
  • Preparation method of metaiodobenzylguanidine (MIBG) sulphate

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preparation example Construction

[0045] The preparation method of m-iodobenzylguanidine sulfate of the present invention prepares the synthetic MIBG sulfate as the labeling precursor of the radiopharmaceutical m-iodobenzylguanidine used in the treatment and diagnosis of neuroendocrine tumors such as human pheochromocytoma and neuroblastoma, Higher security, as can be seen from the above-mentioned preparation method of the present invention, the present invention has abandoned the use of highly toxic reagents such as cyanide, greatly reducing the impact of the production process on personnel and the environment, and at the same time, reducing the highly toxic substances in the final product Residual risk, thus greatly improving the safety of medicines; In addition, the present invention removes the operation of silica gel separation, adopts a large number of recrystallization methods, makes the production operation simple, easy to prepare on a large scale, and has low requirements for the production personnel's ...

Embodiment 1

[0051] Synthetic MIBG sulfate as shown in formula (I),

[0052]

[0053] The synthesis reaction is as follows:

[0054]

[0055] The preparation method is as follows:

[0056] (1) Synthetic intermediate N, N'-(tert-butyloxycarbonyl)-N-(3-iodobenzyl)guanidine

[0057] (1.1) Synthesis of m-iodobromobenzyl

[0058] Take m-iodotoluene 124mmol, N-bromosuccinimide 204mmol and 2,2'-azobisisobutyronitrile 3.42mmol and dissolve in 100mL CCl 4 In the process, the heating temperature is controlled at 80°C to 100°C, and the reflux is performed for 3 to 5 hours; suction filtration, distillation under reduced pressure to remove the solvent, separation by column chromatography, and a light yellow powder product is obtained, the structure of which is the compound metaiodine shown in the following formula (II): Benzyl bromide, the productive rate is 40%; 1 HNMR (400MHz, CDCl 3 )δ7.74(t, J=1.6Hz, 1H), 7.63(d, J=7.9Hz, 1H), 7.36(d, J=7.7Hz, 1H), 7.08(t, J=7.8Hz, 1H) ,4.40(s,2H);

[...

Embodiment 2

[0073] Synthetic MIBG vitriol salt as shown in formula (I), preparation method is as follows:

[0074] (1) Synthetic intermediate N, N'-(tert-butyloxycarbonyl)-N-(3-iodobenzyl)guanidine

[0075] (1.1) Synthesis

[0076] Take m-iodotoluene 124mmol, N-bromosuccinimide 204mmol and 2,2'-azobisisobutyronitrile 3.42mmol and dissolve in 100mL CCl 4 , the heating temperature was controlled at 85°C to 95°C, and refluxed for 4 hours; suction filtration, decompression distillation to remove the solvent, and column chromatography separation gave a light yellow powder product, the structure of which was the compound shown in the following formula (II), and the yield was 39.8%; 1 H NMR (400MHz, CDCl 3 )δ7.74(t, J=1.6Hz, 1H), 7.63(d, J=7.9Hz, 1H), 7.36(d, J=7.7Hz, 1H), 7.08(t, J=7.8Hz, 1H) ,4.40(s,2H);

[0077]

[0078] (1.2) Synthesis

[0079] (1.2.1) Synthesis

[0080] Dissolve 50mmol of S-methylisothiourea sulfate and 100mmol of di-tert-butyl dicarbonate in 125ml of dichlo...

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Abstract

The invention relates to the technical field of radiopharmaceuticals and in particular relates to a preparation method of a radiopharmaceutical *I-metaidobenzylguanidine labelled precursor metaiodobenzylguaidine sulphate applied in the aspects of treatment and diagnosis of neuroendocrine carcinoma including human pheochromocytoma, neuroblastoma and the like. By applying the provided preparation method of MIBG sulphate, MIBG sulphate purity reaches up more than 95%, a technology is simple and optimized compared with the existing MIBG sulphate preparation method, and economic cost is greatly reduced, so that the provided preparation method of MIBG sulphate is applicable to industrial large-scale production application.

Description

technical field [0001] The invention relates to the technical field of radiopharmaceuticals, in particular to a preparation method of the radiopharmaceutical m-iodobenzylguanidine labeled precursor m-iodobenzylguanidine sulfate used in the treatment and diagnosis of neuroendocrine tumors such as human pheochromocytoma and neuroblastoma . Background technique [0002] Pheochromocytoma is a tumor originating from the chromaffin tissue of the neuroectoderm, which mainly secretes catecholamines. According to whether the tumor comes from the sympathetic or parasympathetic nerve, paragangliomas are divided into parasympathetic paragangliomas (including chemoreceptor tumors, carotid artery tumors, etc.) body tumors, etc.) and sympathetic paragangliomas (including retroperitoneal, pelvic and mediastinal paragangliomas). Such tumors can secrete a large amount of catecholamine hormones (such as norepinephrine and adrenaline, etc.) in the body, causing patients to suffer severe heart,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C279/06C07C277/08
Inventor 林春平
Owner BEIJING ZHIBO BIO MEDICAL TECH
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