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

C6-alkylthio/amino substituted pyrimidine derivative and preparation method thereof

A technology of pyrimidine derivatives and alkylthio groups, which is applied in the field of C6-alkylthio/amino-substituted pyrimidine derivatives and their preparation, can solve the problems of lack of downstream operation space, complicated process of special oxidants, limited functional groups of products, etc. , to achieve the effects of cheap and easy availability of raw materials and catalysts, good functional group compatibility, and mild reaction conditions

Pending Publication Date: 2022-04-08
HEBEI UNIV OF TECH
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The purpose of the present invention is to establish an easy-to-obtain α-acyl dihydrogen compound for the problems of noble metals, use of special oxidants, complicated process, harsh conditions, limited functional groups of the product, and lack of downstream operation space in the current synthesis of the lead skeleton pyrimidine. Starting from the raw material of thioketene, using green and abundant ammonium acetate as the nitrogen source, renewable and environmentally friendly alcohols as the C1 source and reaction medium, under the action of a simple copper metal catalyst, a simple and efficient synthesis of C6-alkylthio New approach to amino-substituted pyrimidine derivatives

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
  • C6-alkylthio/amino substituted pyrimidine derivative and preparation method thereof
  • C6-alkylthio/amino substituted pyrimidine derivative and preparation method thereof
  • C6-alkylthio/amino substituted pyrimidine derivative and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Preparation of Heterocyclic Compound 2a

[0030]

[0031] Wherein, SEt and EtS refer to thioethyl;

[0032] Under air conditions, 2-(bis(ethylthio)methylene)-3-oxo-N-phenylbutanamide 2a (309.1mg, 1mmol), ammonium acetate (462mg, 6mmol), copper chloride (13.4mg, 0.1mmol) mixed, added 10ml of methanol solvent, reacted at 90°C for 24h, filtered, extracted, dried, and evaporated under reduced pressure to remove the solvent, then chromatographed on a silica gel column to obtain a white solid 4-( Ethylthio)-6-methyl-N-phenylpyrimidine-5-carboxamide 2a (213.01 mg, yield 78%); relative to the general structural formula, the R of the product obtained in this embodiment 1 is hydrogen, R 2 is methyl, R 3 is an anilide group, R 4 For ethyl.

[0033] 1 H NMR (400MHz, CDCl 3 )δ1.37(t, J=7.2Hz, 3H), 2.50(s, 3H), 3.22(q, J=7.2Hz, 2H), 7.21(t, J=7.2Hz, 1H), 7.40(t, J=7.6Hz, 2H), 7.65(d, J=7.6Hz, 2H), 7.90(s, 1H), 8.79(s, 1H). 13 C NMR (100MHz, CDCl 3)δ14.2, 21.9, 24.4, 120....

Embodiment 2

[0035] Preparation of Heterocyclic Compound 2b

[0036]

[0037] Under air conditions, 2-(bis(ethylthio)methylene)-3-oxobutyramide 2b (233.3 mg, 1 mmol), ammonium acetate (462 mg, 6 mmol), copper chloride (13.4 mg, 0.1 mmol) after mixing, add 10ml of methanol solvent, react at 90°C for 24h, filter with suction, extract, dry, and distill under reduced pressure to remove the solvent, then use silica gel column chromatography to obtain white solid 4-(ethylthio)- 6-methylpyrimidine-5-carboxamide 2b (155.7 mg, yield 79%);

[0038] 1 H NMR (400MHz, DMSO-d 6 )δ1.28(t, J=6.4Hz, 3H), 2.36(s, 3H), 3.16(q, J=7.2Hz, 2H), 7.84(s, 1H), 8.06(s, 1H), 8.82( s, 1H). 13 C NMR (100MHz, DMSO-d 6 )δ14.4, 21.5, 23.3, 129.0, 156.3, 160.0, 165.2, 166.5. HRMS (ESI-TOF) calcd for C 8 h 11 N 3 NaOS + ([M+Na] + )220.0515, found 220.0518.

Embodiment 3

[0040] Preparation of Heterocyclic Compound 2c

[0041]

[0042] Under air conditions, tert-butyl 2-(bis(ethylthio)methylene)-3-oxobutanoate 2c (290 mg, 1 mmol), ammonium acetate (462 mg, 6 mmol), copper chloride (13.4 mg , 0.1mmol) after mixing, add 10ml of methanol solvent, react at 90°C for 24h, filter, extract, dry, and distill under reduced pressure to remove the solvent, then use silica gel column chromatography to obtain yellow oil 4-(ethylsulfide Base)-tert-butyl 6-methylpyrimidine-5-carboxylate 2c (139.9 mg, yield 55%);

[0043] 1 H NMR (400MHz, CDCl 3 )δ1.37(t, J=7.4Hz, 3H), 1.63(s, 9H), 2.51(s, 3H), 3.19(q, J=7.2Hz, 2H), 8.79(s, 1H). 13 C NMR (100MHz, CDCl 3 )δ14.2, 22.7, 24.4, 28.1 (3C), 83.7, 125.5, 156.7, 162.4, 165.1, 168.2. HRMS (ESI-TOF) calcd for C 12 h 18 N 2 NaO 2 S + ([M+Na] + )277.0981, found 277.0972.

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 C6-alkylthio / amino substituted pyrimidine derivative and a preparation method thereof. The structural general formula of the derivative is as shown in formula I in the specification. In the preparation, the C6-alkylthio / amino substituted pyrimidine derivative is synthesized under the action of a simple copper metal catalyst by starting from easily available alpha-acyl ketene dithioacetal, utilizing green and rich ammonium acetate as a nitrogen source and renewable and environment-friendly alcohol as a C1 source and a reaction medium, and the use of noble metal catalysts such as Pt, Ir, Rh and the like is avoided. The operation is simple, the raw materials and the catalyst are cheap and easy to obtain, the reaction condition is mild, the synthesized pyrimidine compound has good functional group compatibility, and an operable space is provided for further functional group derivatization.

Description

Technical field: [0001] The invention belongs to the technical field of organic synthesis chemistry. The invention relates to a C6-alkylthio / amino substituted pyrimidine derivative and a preparation method thereof. Background technique: [0002] Pyrimidine is an important class of heterocyclic compounds, and is the key structural unit of many natural products and drugs, and is widely used in medicine, pesticides, dyes, energy, materials and other fields. Especially in the field of medicine, such as Rosuvastatin (heart disease drug). Therefore, the research and development of the simple and efficient synthesis of multi-substituted pyrimidine heterocyclic derivatives from cheap and easily available raw materials, especially the multi-substituted pyrimidine heterocyclic compounds with potential application value, is a recent priority in the field of synthetic methodology. research focus. [0003] The developed synthetic methods include: Shimizu's research group used Pt / C to ...

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): C07D239/28C07D239/38
Inventor 宋晓宁刘保光王佑坤张笑轩
Owner HEBEI UNIV OF TECH
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