Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Preparation method of 6-fluoro-1H-indazole-4-methyl formate

A technology of methyl formate and methyl nitrobenzoate, applied in the field of medicine, can solve problems such as low safety, high price, and difficulty in industrialization, and achieve the effects of high safety, short reaction steps and low cost

Active Publication Date: 2017-06-16
山东轩德医药科技有限公司
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] 6-Fluoro-1H-indazole-4-carboxylic acid methyl ester is the key intermediate for the preparation of Rucaparib, Organic Process Research and Development; vol.16; nb.12; (2012) introduces the preparation method of Rucaparib and its intermediates , comprehensively discussed the existing technology, and proposed a new synthetic route, but for the preparation of the key intermediate 6-fluoro-1H-indazole-4-carboxylic acid methyl ester, the synthetic method has harsh conditions, and the method of catalytic reduction is adopted, which is safe. Low stability, using metal platinum catalyst, expensive, not easy to industrialize

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
  • Preparation method of 6-fluoro-1H-indazole-4-methyl formate
  • Preparation method of 6-fluoro-1H-indazole-4-methyl formate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Example 1 Preparation of 6-fluoro-1H-indole-4-carboxylhydrazide

[0024]

[0025] In the reaction flask, add DMF (5L), 5-fluoro-2-methyl-3-nitrobenzoic acid methyl ester (1kg, 4.7mol), N,N-dimethylformamide dimethyl acetal ( 3kg, 25.2mol), triethylamine (250g, 2.47mol), after the addition, the temperature was raised to 100 degrees Celsius, the reaction was completed, the temperature was lowered, and rotary steaming was added, methanol (5 liters), 50% hydrazine hydrate (1.4kg, 14.1mol) were added , the temperature was raised to 60 degrees Celsius, the reaction was completed, and a white solid was obtained by filtration, 6-fluoro-1H-indole-4-carboxylhydrazide, 843g, yield: 93.1%.

Embodiment 2

[0026] Example 2 Preparation of 6-fluoro-1H-indazole-4-carboxylic acid methyl ester

[0027]

[0028] Add 6-fluoro-1H-indole-4-carboxylhydrazide (843g, 4.37mol) into the reaction flask, add methanol (1 liter), dichloromethane (5 liters), 2-iodobenzoic acid (1.47kg , 5.25mol), warming up to 40 degrees Celsius, stirring, the reaction is complete, adding 10% sodium sulfite aqueous solution, liquid separation, drying the organic layer, evaporating to dryness, recrystallizing with ethyl acetate and n-heptane to obtain the product 6-fluoro-1H- Indazole-4-carboxylic acid methyl ester, 658g, yield: 78%.

[0029] 1H NMR (400MHz, 25°C, DMSO-d6):

[0030] 3.87(s,3H),6.9(dd,1H,J=0.8,3.1Hz),7.43-7.49(m,2H),7.51(d,1H,J=3.1Hz),11.47(s,br,1H) .

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 invention relates to a preparation method of 6-fluoro-1H-indazole-4-methyl formate. The method has the advantages of simple and convenient reaction process, high safety, high yield and mass production capacity.

Description

[0001] 1. Technical field [0002] The invention belongs to the technical field of medicine, and relates to a preparation method of methyl 6-fluoro-1H-indazole-4-carboxylate. [0003] 2. Background technology [0004] Rucaparib, an ovarian cancer treatment drug, was granted FDA breakthrough drug designation in 2015 and is suitable for its third-line application in ovarian cancer. The spread of certain genetic mutations occurs. The FDA granted Breakthrough Therapy Designation to rucaparib for the treatment of patients with BRCA-mutated advanced ovarian cancer who had previously failed second-line therapy. In May 2016, a new drug listing application was submitted in the United States for the study of Rucaparib for the treatment of ovarian cancer. [0005] 6-Fluoro-1H-indazole-4-carboxylic acid methyl ester is the key intermediate for the preparation of Rucaparib, Organic Process Research and Development; vol.16; nb.12; (2012) introduces the preparation method of Rucaparib and i...

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): C07D209/08
CPCC07D209/08
Inventor 董岩岩
Owner 山东轩德医药科技有限公司
Features
  • Generate Ideas
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com