4-Amino-2-substituted thieno

More recently (2001 JHCl 167), this approach was extended to the synthesis of 0X0- and amino-substituted thieno[2,3-()]thiophenes. Compounds containing an active methylene group (3-keto esters, malononitrile, ethyl cyanoacetate or 3-ketonitrile) were used as the starting reagents, and ethyl bromoacetate or bromoacetonitrile served as the alkylating agent. The yields of thienothiophenes were 61-87%. 

Organolithium derivatives served as intermediates in the synthesis of 5-amino-substituted thieno[2,3-Z ]- and -[3,2- >]thiophene-2-sulfonamides possessing biological... 

In 1962 Gompper, Kutter, and Topfl prepared substituted thieno-thiophenes (1) from dithiocarboxylate s ts. With haloacetic acid derivatives these give ketenemercaptals (104), which are easily converted by base into 3-amino- and 3-hydroxythiophenes (105). Further cyclization of 105 results in substituted thienotMophenes 106, which may also be obtained directly by heating the dithiocarboxylates with haloacetic acid derivatives in alcoholic sodium alkoxide (Scheme 7). 

Cycloaddition and cyclization routes were used to access certain 1,3-diazines. The 4+2 cycloaddition reaction of 4-(N-allyl-N-aryl)amino-l,3-diaza-l,3-butadienes with vinyl-, isopropenyl-, and chloroketene led to pyrimidinone-fused pyrimidinones <97T13841>. Cis-cyclopenta[d]pyrimidines were derived from cis-2-amino-l-cyclopentanecarboxylates by cyclization with KOCN and KSCN <97JHC1211>. 2-Thioxopyrido[3, 2 4,5]thieno[3,2-r/]pyrimidin-4(3//)-ones 19 were prepared by cyclocondensation of 2-carbethoxy-3-amino-4-phenyl-6-substituted-thieno[2,3-/)]pyridines and isothiocyanates <97JHC937>. Thiazolyl-benzimidazoles derived from 2-cyanomethyl-l//-benzimidazole and 2,3-dihydrothiazole-2-(3//)-thiones were cyclized to the corresponding thiazolo[4,5-r/]pyrimidines <97PHA346>. Reductive cyclization of 6-cyanomethyl-5-nitropyrimidines afforded 7-alkyl-5//-pyrrolo[3,2-r/]pyrimidines and 6-amino-7,7-dialkyl-7//-pyrrolo[3,2-rf]pyrimidines <97T391>. 7-Methyl-5-alkyl-2-vinyl-pyrazolo[3,4-r/]pyrimidine-4,6(5//,7//)-diones arose from cyclization and alkylation of... 

Amino and imino groups. Amino thieno benzoxepine 163 (Scheme 32, Section 2.2.3) can be smoothly transformed into the corresponding amides and urea (1994JCS(P1)2191). The dimethylamino substituted pyrrolo-benzoxazepine... 

The amino group of 10H-benzo[i7]thieno[2,3-e][l,4]diazepin-4-amine 253 can be substituted with N-methyl piperazine by direct amination under thermal conditions (Scheme 53, Section 3.1.3 (1997BMCL25)). 

A photocyclization of 3-(2-pyrrolyl)-3-amino-2-alkeneimines under acidic reaction conditions leads to the formation of pyrrolo[3,2-3]pyridine as shown in Equation (22) <1999T14079>. When oxygen or sulfur heteroatoms are substituted for the pyrrole ring nitrogen, the corresponding furo- and thieno[3,2-3]pyridines are formed. All of the photocyclizations require lengthy reaction times and the yields tend to be low, especially for the furopyridine derivatives. 

Dichloro-5-methoxyphenyl)amino]thieno[3,2- ]pyridine-6-carbonitriles substituted with heteroaryl groups at position C-2, 160, have been found to inhibit Src kinase activity. The highest activity in Src and cell assays has been found with a 2,5-furan or 2,5-pyridine substituent at C-2 <2005BML4681, 2005JME3891>. 

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>. 

Thieno[3,2-fc]pyridines are obtained in 49-87% yield (74JPR169). Application of the Friedlander reaction to 3-amino-2-formylthiophene gives (261) in reasonable yield (Scheme 78) (75ACS(B)224,75 ACS(B)233). As in the case of the synthesis of furo[3,2- >]pyridines (Section 3.17.2.1.1(i)(d), Scheme 17), it was unnecessary to isolate the o-aminocarbonyl compounds. 6-Substituted 7-hydroxythieno[3,2-6]pyridin-5(4/7)-ones (e.g. 295) can be prepared by base-catalyzed cyclization of the amides (294), which were obtained in high yields from readily available 3-amino-2-alkoxycarbonylthiophenes (293 Scheme 79) (80JCR(S)6) for... 

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]

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. 

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