2-Amino-3-cyano- thiophene

Amino-3-cyano-thiophenes or 2-amino-thiophene-3-esters result from this route, generally conducted as a one-pot process, involving a ketone that has an a-methylene, ethyl cyanoacetate or malononitrile, sulfur, and morpholine. Various improvements to the original procedure include using microwave irradiation on solid snpport, or with potassium fluoride on alumina as the base, or solvent-free,and using morpho-lininm acetate in excess morpholine for aryl alkyl ketones. 

Thieno[2,3- /]pyrimidines have been synthesized from 5-acylamino-2,3-dialkylthiophen-4-aldehydes. 2-Amino-3-cyano-thiophens have been transformed into the 2-cyanamino-3-cyano-thiophens and ring-closed to 4-aminothieno[2,3-Raney nickel to the 4-oxo-pyrimidine (263). ... 

Successive treatment of 2-amino-3-cyanothiophenes 30 with carbon disulfide in the presence of sodium methoxide and then with methyl iodide gave w c-Z>A(methyl-thio)methylideneamino(cyano)thiophenes 68, which were transformed into al-kylthiothienopyrimidineimines 69 under the action of amines (1993JCR(S)302). It was emphasized that it is necessary to thoroughly control the reaction conditions to prevent the possible Dimroth rearrangement. 

When the enolate is that derived from malononitrile, 3-amino-4-cyano-thiophenes are the result. ... 

Thiophene, 3-amino-2-benzoyl-4-cyano-5-hydroxy synthesis, 4, 927... 

Thiophene, 2-amino-3-cyano-5-phenyl-synthesis, 4, 888-889 Thiophene, 3-amino-4,5-dihydro-cycloaddition reactions, 4, 848 Thiophene, 2-amino-3-ethoxycarbonyl-ring opening, 4, 73 Thiophene, 2-amino-5-methyl-synthesis, 4, 73 Thiophene, 2-anilino-synthesis, 4, 923-924 Thiophene, aryl-synthesis, 4, 836, 914-916 Thiophene, 2-(arylamino)-3-nitro-synthesis, 4, 892 Thiophene, azido-nitrenes, 4, 818-820 reactions, 4, 818-820 thermal fragmentation, 4, 819-820 Thiophene, 3-azido-4-formyl-reactions... 

Thiophene-2-carboxamide, 3-amino-diazotization, 4, 810 Thiophene-2-carboxamide, 5-cyano-synthesis, 4, 898, 920... 

Chakrabarti and coworkers at Eli Lilly in the United Kingdom have reported the initial discovery and synthesis of olanzapine (Schemes 5 and,6). The thiophene 22 was synthesized by adding a DMF solution of malononitrile to a mixture of sulfur, propionaldehyde and triethylamine in DMF. The anion of amino thiophene 22 underwent a nucleophilic aromatic substitution with 2-fluoronitrobenzene to provide 23. The nitro group was reduced with stannous chloride and the resulting anihne cyclized with the cyano group to form amidine 24. Finally, a mixture of N-methylpiperazine and 24 were refluxed in DMSO/toluene to afford olanzapine (2). 

Thiophene, 2-acyl-3-amino-5-aryl-4-cyano-synthesis, 4, 897 Thiophene, alkenyl-synthesis, 4, 917 Thiophene, alkoxy-synthesis, 4, 929 Thiophene, 2-alkoxy-5-aryl-synthesis, 4, 929 Thiophene, alkyl-... 

Virtually all of the syntheses of thieno[2,3-synthetic strategy. Thus, thiophenes with a 2-amino- (or (substituted)amino-) function, and either a carboalkoxy, carboxamido, or a cyano group at 03 are the preferred starting points. Typically, when the thiophene has a carbonyl function at 03 (268 R = OEt or NH2) cyclization affords the 4-oxothienopyrimidines (269) (Equation (93)). 

Decarboxylation of 5,7-dimethyl-8-oxo-6-aza-8//-indeno[2,1 - ]thiophene-4-carboxylic acid could be effected by heating an admixture of it and copper powder <87H(26)1535). Direct sublimation in vacuo afforded the desired product (58%). 9-Chloro-2- and 3-methyltriazolo[4,5-/]quinoline-7-carboxylic acids are decarboxylated under similar conditions <93H(36)259>. The cyano group of 8-cyano-7-oxo-4,5,6,7-tetrahydrothiazolo[4,5-/]quinolines can be converted into an amino group by cone. HC1 mediated hydrolysis to the amide, followed by Hofmann rearrangement <89H(29)I517>. 

Trioxopyrido[3,2, 4,5]thieno[3,2-<7]pyrimidin-4(3//)-ones were synthesized by the reactions of 3-amino-2-ethoxycarbonylthieno[2,3-Z>]pyridines with isothiocyanates (1997JHC937) or by the reactions of 3-amino-2-cyano(carbamoyl)thieno[2,3-Z>]pyridines with carbon disulfide (1998M523). An analogous reaction of 2-amino-thiophene-3-carboxamide with carbon disulfide yielded thioxopyrimidinone 10 (1990PS181, 1993MI1). 

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