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

Synthesis method for 6-amino-2,2-dimethyl-2H-pyridino-[3,2-b] [1,4] oxazine-3(4H)-ketone

A technology of dimethylformamide and acetone, applied in the direction of organic chemistry, can solve the problems of inability to produce on a large scale, difficulty in purification of intermediates, low yield, etc.

Active Publication Date: 2014-04-09
PHARMABLOCK SCIENCES (NANJING) INC
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It mainly solves the problem of low yield of existing 6-amino-2,2-dimethyl-2H-pyridin[3,2-b][1,4]oxazin-3(4H)-one, difficult purification of intermediates, and inability to Technical issues of mass 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 more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Synthesis method for 6-amino-2,2-dimethyl-2H-pyridino-[3,2-b] [1,4] oxazine-3(4H)-ketone
  • Synthesis method for 6-amino-2,2-dimethyl-2H-pyridino-[3,2-b] [1,4] oxazine-3(4H)-ketone
  • Synthesis method for 6-amino-2,2-dimethyl-2H-pyridino-[3,2-b] [1,4] oxazine-3(4H)-ketone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Synthesis of 2,2-Dimethyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Compound 3)

[0030]

[0031] Dissolve 2-amino-3-hydroxypyridine (450.0 g, 4.086 mol, 1.0 eq) in 6750 mL of acetone, add potassium carbonate (1.7 kg, 12.26 mol, 3.0 eq) and ethyl 2-bromo-2-methylpropanoate Ester (1036g, 5.312mol, 1.3eq), heated and stirred under reflux for 24h. After cooling, add to ice water in batches, stir, suction filter and wash the filter cake three times, drain and dry to obtain 630 g of off-white solid with a yield of 86.5%. used directly in the next reaction.

[0032] 1 HNMR (400MHz, CDCl3) δ: 1.09(s, 1H), 8.07-8.09(q, 1H), 7.26-7.28(q, 1H), 6.95-6.99(q, 1H), 1.58(s, 6H).

[0033] Synthesis of 2,2-Dimethyl-6-nitro-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (compound 6)

[0034]

[0035] Compound 3 (580 g, 3.255 mol, 1.0 eq) was added in batches to 3000 mL of concentrated sulfuric acid in an ice-salt bath, and the temperature dropped to below 0°C due to exothermic phenomenon. ...

Embodiment 2

[0042] Synthesis of 2,2-Dimethyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Compound 3)

[0043]

[0044] Dissolve 2-amino-3-hydroxypyridine (5.0 g, 45.4 mmol, 1.0 eq) in 25 mL of methanol, add potassium carbonate (18.8 g, 136.2 mmol, 3.0 eq) and ethyl 2-bromo-2-methylpropanoate Ester (13.28g, 68.1mmol, 1.5eq), heated and stirred under reflux for 18h. After cooling, add to ice water in batches, stir, filter with suction and wash with water three times, drain and dry to obtain 5.21 g of off-white solid with a yield of 64%.

[0045] 1 HNMR (400MHz, CDCl3) δ: 1.09(s, 1H), 8.07-8.09(q, 1H), 7.26-7.28(q, 1H), 6.95-6.99(q, 1H), 1.58(s, 6H).

[0046] Synthesis of 2,2-Dimethyl-6-nitro-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Compound 6)

[0047]

[0048]Compound 3 (5.0 g, 28.06 mmol, 1.0 eq) was added in batches to 15 mL of concentrated sulfuric acid in an ice-salt bath, and the temperature dropped to below 0° C. due to exothermic phenomenon. Prepare mixed acid: Add 5 mL of concen...

Embodiment 3

[0055] Synthesis of 2,2-Dimethyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Compound 3)

[0056]

[0057] Dissolve 2-amino-3-hydroxypyridine (5.0 g, 45.4 mmol, 1.0 eq) in 25 mL of DMF, add potassium carbonate (18.8 g, 136.2 mmol, 3.0 eq) and ethyl 2-bromo-2-methylpropanoate Ester (13.28g, 68.1mmol, 1.5eq), heated to 60°C and stirred for 18h. After cooling, add to ice water in batches, stir, filter with suction and wash with water three times, drain and dry to obtain 5.66 g of off-white solid with a yield of 70%.

[0058] 1 H NMR (400 MHz, CDCl3) δ: 1.09 (s, 1H), 8.07-8.09 (q, 1H), 7.26-7.28 (q, 1H), 6.95-6.99 (q, 1H), 1.58 (s, 6H).

[0059] Synthesis of 2,2-Dimethyl-6-nitro-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Compound 6)

[0060]

[0061] Compound 3 (5.0 g, 28.06 mmol, 1.0 eq) was added in batches to 15 mL of concentrated sulfuric acid in an ice-salt bath, and the temperature dropped to below 0° C. due to exothermic phenomenon. Prepare mixed acid: Add 5 mL of concentr...

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 the field of chemical synthesis, in particular to a synthesis method for 6-amino-2,2-dimethyl-2H-pyridino-[3,2-b] [1,4] oxazine-3(4H)-ketone, which is characterized by including the steps of carrying out percyclic reaction of 2-amino-3-hydroxypyridine serving as a raw material and 2-bromine-2-methyl propionic acid ethyl in the presence of potassium carbonate, then dropwise adding mixed acid of concentrated sulfuric acid and fuming nitric acid into a reaction system, selectively obtaining 2,2-dimethyl-6-nitryl-2H-pyridino-[3,2-b] [1,4] oxazine-3(4H)-ketone by means of nitration, and finally obtaining a target compound after reduction. The synthesis method has the advantages of high yield, mild reaction conditions and the like, and has large-scale preparation value.

Description

Technical field: [0001] The invention relates to the field of chemical synthesis, in particular to a synthesis method of 6-amino-2,2-dimethyl-2H-pyridin[3,2-b][1,4]oxazin-3(4H)-one. Background technique [0002] 6-Amino-2,2-dimethyl-2H-pyridin[3,2-b][1,4]oxazin-3(4H)-one is a useful drug intermediate, and JP2008013527 reports that it contains such The compound of the core structure is spleen tyrosine kinase (Spleen tyrosine kinase, Syk), which plays an important role in the maturation of lymphocytes and the activation of immune cells. Syk may become a target for the treatment of lymphoma, leukemia and other tumors related to the immune system. [0003] For the preparation of 6-amino-2,2-dimethyl-2H-pyridin[3,2-b][1,4]oxazin-3(4H)-one, the methods of related compounds reported in literature are as follows: [0004] Method JP2008 / 013527A reports two preparation methods, which are as follows: [0005] method one: [0006] [0007] Reagents and yield: (I) sodium methoxide...

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
Patent Type & Authority Patents(China)
IPC IPC(8): C07D498/04
Inventor 夏爱华潘光新周西朋吴希罕杨民民
Owner PHARMABLOCK SCIENCES (NANJING) INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com