Chapter I. Synthesis, modification and bioactivity of bicyclic thieno[3,2-D]pyrimidines

CHAPTER I. SYNTHESIS, MODIFICATION AND BIOACTIVITY OF BICYCLIC THIENO[3,2-D]PYRIMIDINES

1.1 Synthesis of thiopyrimidine derivatives
Synthesis of thiopyrimidine is formed by combining two main starting products: firstly, thiopyrimidine derivatives react with thiophene ring as substance, and secondly, thiopyrimidine derivatives react with pyrimidine ring as substance[1-14].
1.1.2 Synthesis of pyrimidine derivatives with the participation of thiophene and pyrimidine rings
There are a lot of way to synthesis of pyrimidine derivatives with the participation of thiophene and pyrimidine ring. The first way to synthesis: In the above-mentioned reaction, the synthesis of thiophene derivatives was first carried out. In this case, R can optionally be alkyls or aryls, and this process requires 2 more terms and one process. After the formation of the thiophene derivative, the phenyl radical is attached, and in this process, the thiophyrimidine derivative is formed. In this case, instead of conditionally defined A in the resulting substance, there may be O, N, S and other elements as shown in the reaction, and depending on the composition and properties of the substance we need, we can synthesize any of them. We can analyze these processes more fully as follows

1.1.3 Synthesis of 4-Substituted 3-Amino-2- cyanothiophenes 1
We can see the reaction system given for this reaction in two ways, i.e. the first view given in the literature, we can see the view of practical realization A, we can also see the two stages of this process B[15, 16].
A-scheme

It is better to call this stage the stage given in the literature, that is, this stage was first implemented and is present in many literatures. We can say that the second stage is completed.
This second B reaction is an important step with LDA
B-scheme

1.1.4 Proposed Synthesis of 1 Using O-Ethyl Thioformate
It is noteworthy that O-ethyl thioformate has been used to generate thioformamides which are synthetically useful intermediates for the synthesis of various heterocycles,8 thioamides, 9 iminyl sulfides, 10 enamines, 11 and amines. 12 However, it was only recently, as reported by Borths, that the preparation of O-ethyl thioformate became readily achievable at a large scale and in high yield.To our great delight, when 2-alkyl or aryl substituted acetonitriles were sequentially treated at −40 °C with LDA, O-ethyl thioformate (A), and 2- chloroacetonitrile (B), the desired thiophene product 1 was indeed produced[17].

This reaction process describes as and that reaction substance use for synthies was result of cycle.
The next reaction process demonstrates us to syntheses situation and mechanism for reaction

The mechanism for this process, illustrated using benzyl cyanide (2g) as a representative example, involves the deprotonation of nitrile 2g, followed by a Claisen-like nucleophilic addition of the resulting anion to O-ethyl thioformate to generate thiolate 7 when 1 equiv of LDA was employed. The second equivalent of LDA then promotes an elimination reaction of thiolate 7 to afford an ethoxide and thiolate 5a. Upon treatment with 2-chloroacetonitrile, thiolate 5a is readily converted to a mixture of isomeric vinyl thiolates (6a and 6b).
An ethoxide anion promotes not only the isomerization of E-thiolate 6b to Z-thiolate 6a but also the facile cyclization of Z-thiolate 6a to the cyclized intermediate 9, which quickly undergoes tautomerization to form the desired thiophene 1g.[18, 19].