2-Amino-7- thieno pyrimidine

Other variants of this type of ring system are obtained by simple (S -type ) cyclization of the (3-hydroxypropyl-amino)thieno[2,3- /]pyrimidines 475 (Equation 202) <2000PS( 165)221 > and reaction of the parent aminopyrimidine with the enol ether 476 under microwave irradiation (Equation 203) <1999H(51)1819>. 

Chloroacetylation of the amino group provides an intermediate that can be cyclized to 2-substituted-4-amino thieno[2,3- pyrimidines upon treatment with KSCN <1996JPR206>. 

Ring chlorination of 2-amino(or substituted amino)thieno[3,4-d]pyrim-idin-4(3//)-ones 370 (90EUP404356) and 5,7-dihydro-2-(2-methylanilino) thieno[3,4-c/]pyrimidin-4(3//)-one 372 (91MIP1) in boiling phosphoryl chloride gave the respective 4-chloro compounds 371 (90EUP404356) and 373 (91MIP1). The displacement of chlorine from both these compounds by a variety of nucleophiles was also reported. 

Thieno[2,3-d]pyrimidine, 4-amino-synthesis, 4, 1017, 1018 Thieno[2,3-d]pyrimidine, 4-chloro-synthesis, 4, 1017... 

Zinc dust has been used to reduce a tetrazole of the tricyclic system 57 to generate the corresponding bicyclic 2-amino-3,5,6-trimethyl-3//-thieno[2,3- /]pyrimidin-4-one 58 (Equation 8) <2000MOL835>. 

Conversion of the amino group into a Schiff base intermediate offers yet another method for preparing thieno[2,3-41-pyrimidines. Sucl <2004JOC8366>. 

Isolated examples of syntheses of thieno[2,3-,7 pyrimidines commencing with either amino- or nitrothiophene possessing no other functionality have been described <2004CHE370, 1996J(P1)417, 1996J(P1)1403>. 

The examples above open up synthetic approaches that involve manipulating either the amino or carboalkoxy moieties. The following examples illustrate the variety of ways in which these transformations have been used to synthesize thieno[3,2-4 pyrimidines. Scheme 37 describes one such method in which an intermediate urea derivative 456 is formed from 455 by reaction with ethyl isothiocyanatoformate. Cyclization to 457 occurs upon heating in an ethanolic alkoxide medium <2003BML107>. 

Analogs of 457 that possess a sulfur atom at position 2 have also been prepared in a similar way <2002MI717>. The use of thiophene isothiocyanates has also been valuable in the formation of thieno[3,2-t/ pyrimidines. Treatment of 458 with (A)-(- -)-2-amino-l-propanol at reflux in the presence of KOBu produces 459a (Equation 171). 

A widely used method of preparing 3-amino-2-unsubstituted thieno-[2,3-d]pyrimidines 49a is by condensing o-aminocarbonitriles 48 with forma-mide (83MI1 86KFZ39 88JPR585 89MI2 90MI5). On the other hand,... 

Starting from 2-amino-3-cyano-4,5-dihydrothiophenes 60 the derived 2-benzamido derivatives 61 were treated with cyclohexylamine, morpholine, piperidine, or pyrrolidine to yield the respective 5,6-dihydro-2-phenyl 4-substituted aminothieno[2,3-d]pyrimidines 62a-d (83CPB401). In the presence of tin(IV) chloride, benzamides 61 reacted with acetic (or propionic) anhydride to give the corresponding 3-acetyl(or propionyl)thieno[2,3-[Pg.206]

When o-aminocarbonitriles 48 (R2 = R3 = Me) or 52 were reacted with jY-arylcyanamides in the presence of dry hydrogen chloride gas followed by aqueous workup, a mixture of 2-amino-3-aryl-4-iminothieno[2,3-d]-pyrimidines 65d and the corresponding thieno[2,3-d]pyrimidin-4(3//)-ones 66b was isolated. The formation of the latter as a minor product for each derivative was rationalized to proceed via the guanidine intermediate 67, which hydrolyzed through a Ritter-type reaction and then cyclized during workup (93JHC435). 

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