DD237663A1 - PROCESS FOR PREPARING 4-BASED SUBSTITUTED THIENO / 2,3-D / PYRIMIDIN-2-YLCARBONESAEUREDERIVATES - Google Patents

PROCESS FOR PREPARING 4-BASED SUBSTITUTED THIENO / 2,3-D / PYRIMIDIN-2-YLCARBONESAEUREDERIVATES Download PDF

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DD237663A1
DD237663A1 DD27250785A DD27250785A DD237663A1 DD 237663 A1 DD237663 A1 DD 237663A1 DD 27250785 A DD27250785 A DD 27250785A DD 27250785 A DD27250785 A DD 27250785A DD 237663 A1 DD237663 A1 DD 237663A1
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pyrimidin
general formula
alkyl
polymethylene
compounds
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DD27250785A
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German (de)
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Ralf Boehm
Reinhard Pech
Jutta Mertens
Dieter Lohmann
Gunter Laban
Horst Nindel
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Univ Halle Wittenberg
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Abstract

Die Erfindung betrifft ein Verfahren zur Herstellung von 4-basischsubstituierten Thieno/2,3-d/pyrimidin-2-ylcarbonsaeurederivaten der allgemeinen Formel I, worin R1, R2alkyl, polymethylen, R3alkoxy, alkylamino, dialkylamino, arylamino, R4, R5H, alkyl, phenyl, substituiertes phenyl bedeuten. Diese Verbindungen stellen potentielle Pharmaka dar und sind gleichzeitig Zwischenprodukte der pharmazeutischen Industrie. Ziel der Erfindung ist es, ausgehend von 5,6-disubstituierten 3,4-Dihydro-4-oxothieno/2,3-d/pyrimidin-2-ylcarbonsaeureestern der allgemeinen Formel II, worin R1, R2alkyl, polymethylen, R3alkoxy bedeuten, 4-basischsubstituierte Thieno/2,3-d/pyrimidin-2-ylcarbonsaeurederivate darzustellen. Die Synthese der Verbindungen der allgemeinen Formel I erfolgt durch Umsetzung der Verbindungen der allgemeinen Formel II mit Phosphoroxidchlorid, wobei die anfallenden 4-Chlorderivate der allgemeinen Formel III anschliessend mit primaeren oder sekundaeren Aminen in einem polar protischen organischen Loesungsmittel zur Reaktion gebraucht werden.The invention relates to a process for the preparation of 4-basic-substituted thieno / 2,3-d / pyrimidin-2-ylcarboxylic acid derivatives of general formula I in which R1, R2alkyl, polymethylene, R3alkoxy, alkylamino, dialkylamino, arylamino, R4, R5H, alkyl, phenyl, substituted phenyl. These compounds are potential drugs and are also intermediates in the pharmaceutical industry. The aim of the invention is, starting from 5,6-disubstituted 3,4-dihydro-4-oxothieno / 2,3-d / pyrimidin-2-ylcarbonsaeureestern the general formula II, wherein R1, R2alkyl, polymethylene, R3alkoxy mean, 4th basic substituted thieno / 2,3-d / pyrimidin-2-ylcarboxylic acid derivatives. The synthesis of the compounds of general formula I is carried out by reacting the compounds of general formula II with phosphorus oxychloride, wherein the resulting 4-chloro derivatives of general formula III are subsequently used with primary or secondary amines in a polar protic organic solvent for reaction.

Description

Anwendungsgebiet der ErfindungField of application of the invention

Die Erfindung betrifft ein Verfahren zur Synthese von 4-basischsubstituiertenThieno/2,3-d/pyrimidin-2-ylcarbon-säurederivaten der allgemeinen Formel I,The invention relates to a process for the synthesis of 4-basic-substituted thieno / 2,3-d / pyrimidin-2-ylcarbon-acid derivatives of the general formula I,

worin R1, R2 = alkyl, polymethylen,wherein R 1 , R 2 = alkyl, polymethylene,

R3 = alkoxy, alkylamino,dialkylamino, arylamino,R 3 = alkoxy, alkylamino, dialkylamino, arylamino,

R4, R6 = H, alkyl, phenyl, substituiertes phenyl, aralkyl, polymethylen bedeutenR 4 , R 6 = H, alkyl, phenyl, substituted phenyl, aralkyl, polymethylene mean

Die Verbindungen stellen potentielle Pharmaka und gleichzeitig Zwischenprodukte der pharmazeutischen Industrie dar. The compounds are potential drugs and also intermediates of the pharmaceutical industry.

Charakteristik der bekannten technischen LösungenCharacteristic of the known technical solutions

Verbindungen der allgemeinen Formel I sind bisher weder in der Patent- noch in der Fachliteratur beschrieben worden. Beschrieben werden lediglich 3,4-Dihydro-4-oxothieno/2,3-d/-pyrimidin-2-ylcarbonsäuren, deren Ester bzw. Salze. Eine Derivatisierung dieser für die vorgelegte Erfindung als Ausgangssubstanzen dienenden Strukturen wird bisher in keiner Literaturangabe erwähnt (CH 638527, FP 2401164, GB 1583679, US 4054656, US 4159377, US 4234581, DD 0152129). Patente, bei denen Esterstrukturen über ein Schwefelatom an den Heterocyclus gebunden sind, berühren die vorgelegte Erfindung nicht (FR 2332992, DE 2654090).Compounds of the general formula I have hitherto not been described either in the patent or in the specialist literature. Described are only 3,4-dihydro-4-oxothieno / 2,3-d / -pyrimidin-2-ylcarboxylic acids, their esters or salts. A derivatization of these structures used as starting materials for the present invention is not mentioned in any literature reference (CH 638527, FP 2401164, GB 1583679, US 4054656, US 4159377, US 4234581, DD 0152129). Patents in which ester structures are bonded to the heterocycle via a sulfur atom do not affect the present invention (FR 2332992, DE 2654090).

Ziel der ErfindungObject of the invention

Ziel der Erfindung ist eine einfache und schnelle Herstellungsmethode für bisher nicht zugängliche 4-basischsubstituierte Thieno/2,3-d/pyrimidin-2-ylcarbonsäurederivate der allgemeinen Formel I mit gut zugänglichen Ausgangsprodukten, um die Palette potentieller Pharmaka bzw. interessanter Zwischenprodukte zu erweitern.The aim of the invention is a simple and rapid production method for hitherto inaccessible 4-basic-substituted thieno / 2,3-d / pyrimidin-2-ylcarbonsäurederivate the general formula I with readily available starting materials to expand the range of potential drugs or interesting intermediates.

Darlegung des Wesens der ErfindungExplanation of the essence of the invention

Aufgabe der Erfindung ist ein Verfahren zur Synthese von 4-basischsubstituierten Thieno/2,3-d/pyrimidin-2-ylcarbonsäurederivaten der allgemeinen Formel I, worin R1, R2 = alkyl, polymethylen,The object of the invention is a process for the synthesis of 4-basic-substituted thieno / 2,3-d / pyrimidin-2-ylcarboxylic acid derivatives of the general formula I in which R 1 , R 2 = alkyl, polymethylene,

R3 = alkoxy, alkylamino,dialkylamino, arylamino,R 3 = alkoxy, alkylamino, dialkylamino, arylamino,

R4, R5 = H, alkyl, phenyl, substituiertes phenyl, aralkyl, polymethylen bedeuten.R 4 , R 5 = H, alkyl, phenyl, substituted phenyl, aralkyl, polymethylene mean.

Erfindungsgemäß wird die Aufgabe dadurch gelöst, daß 5,6-disubstituierte 3,4-Dihydro-4-oxothieno/2,3-d/pyrimidin-2-ylcarbonsäureester der allgemeinen Formel II, worin R1, R2 = alkyl, polymethylen,According to the invention the object is achieved in that 5,6-disubstituted 3,4-dihydro-4-oxothieno / 2,3-d / pyrimidin-2-ylcarbonsäureester of the general formula II, wherein R 1 , R 2 = alkyl, polymethylene,

R3 = alkoxy bedeuten,R 3 = alkoxy,

mit Phosphoroxidchlorid in Gegenwart von N,N-Dimethylanilin in der Siedehitze zu 5,6-disubstituierten 4-Chlorthieno-/2,3-d/ pyrimidin-2-ylcarbonsäureestern umgesetzt werden. Diese 5,6-disubstituierten 4-Chlorthieno/2,3-d/pyrimidin-2-ylcarbonsäureester der allgemeinen Formel III, worin R1, R2 = alkyl, polymethylen,be reacted with phosphorus oxychloride in the presence of N, N-dimethylaniline in the boiling heat to 5,6-disubstituted 4-chlorothieno- / 2,3-d / pyrimidin-2-ylcarbonsäureestern. These 5,6-disubstituted 4-chlorothieno / 2,3-d / pyrimidin-2-ylcarboxylic esters of general formula III, wherein R 1 , R 2 = alkyl, polymethylene,

R3 = alkoxy bedeutenR 3 = alkoxy

werden mit einem Amin in einem polar protischen organischen Lösungsmittel in der Siedehitze umgesetzt. Dabei wird entweder das Chloratom in4-Position allein gegen eine Aminogruppe ausgetauscht oder gleichzeitig die Esterstrukturin 2-Position in eine Amidgruppierung umgewandelt, wobei die 4-basischsubstituierten Thieno/2,3-d/pyrimidin-2-ylcarbonsäurederivate der allgemeinen Formel I, worin R1, R2, R3, R4, R5 obige Bedeutung besitzen, gebildet werden. Die Aufarbeitung der erhaltenen Produkte erfolgt in an sich bekannter Weise.are reacted with an amine in a polar protic organic solvent at boiling heat. Either the in4-position chlorine atom alone is replaced by an amino group, or at the same time the 2-position ester structure is converted to an amide moiety, with the 4-basic substituted thieno / 2,3-d / pyrimidin-2-ylcarboxylic acid derivatives of general formula I, wherein R 1 , R 2 , R 3 , R 4 , R 5 have the above meaning be formed. The workup of the resulting products is carried out in a conventional manner.

Ausführungsbeispieleembodiments

Die Erfindung soll nachfolgend an drei Ausführungsbeispielen erklärt werden:The invention will be explained below with reference to three embodiments:

Beispiel 1example 1

4-Chlor-5,6-dimethylthieno/2,3-d/pyΓimidin-2-ylcarboπsäure-ethylester, C11H11CIN2O2S (270,7) Ein Gemisch aus 0,01 mol ö^-Dimethyl^-oxo-SAdihydrothieno^S-d/pyrimidin^-ylcarbonsäureethylester, 0,5ml N,N-Dimethylanilin und 6ml POCI3 wird 14h unter Rückfluß erhitzt. Der abgekühlte dickflüssige Rückstand wird anschließend in Wasser verrührt und die Suspension mit Natriumkarbonat neutralisiert. Nach dem Absaugen reinigt man säulenchromatographisch (Elutionsmittel Chloroform).4-Chloro-5,6-dimethylthieno / 2,3-d / pyiumimidin-2-ylcarboxylic acid ethyl ester, C 11 H 11 CIN 2 O 2 S (270.7) A mixture of 0.01 mol of ethyldimethyl -oxo-S-dihydro-thieno ^ Sd / pyrimidine-ethylcarboxylate, 0.5 ml of N, N-dimethylaniline and 6 ml of POCl 3 are refluxed for 14 h. The cooled viscous residue is then stirred in water and the suspension neutralized with sodium carbonate. After filtration with suction, it is purified by column chromatography (eluent chloroform).

Schmelzpunkt: 124-1260C, Ausbeute: 67%Melting point: 124-126 0 C, yield: 67%

Analog wird hergestellt:Analog is produced:

4-Chlor-5,6-tetramethylenthieno/2,3-d/pyrimidin-2-ylcarbonsäureethyiester, C13H13CIN2O2S (296,8)4-Chloro-5,6-tetramethylenethieno / 2,3-d / pyrimidin-2-ylcarboxylic acid ethyl ester, C 13 H 13 CIN 2 O 2 S (296.8)

Schmelzpunkt: 132-133°C, Ausbeute: 70%Melting point: 132-133 ° C, yield: 70%

Beispiel 2Example 2

4-(subst.) Aminothieno/2,3-d/pyrimidin-2-ylcarbonsäureester4- (substituted) aminothieno / 2,3-d / pyrimidin-2-ylcarboxylic acid ester

Ein Gemisch aus 0,005mol 4-Chlorthieno/2,3-d/pyrimidin-2-ylcarbo.ns'äureethylester und 0,015mol primäres aromatisches, aliphatischesodersekundäraliphatisches Amin werden 4-7 h in 8 ml Ethanol unter Rückfluß gekocht. Danach wird der Niederschlag abgesaugt, mit Wasser gewaschen und aus Ethanol umkristallisiert. In einigen Fällen ist eine säulenchromatographische Reinigung notwendig (Aluminiumoxid/neutral, Elutionsmittel: Methylenchlorid).A mixture of 0.005 moles of 4-chlorothieno / 2,3-d / pyrimidin-2-ylcarboxylic acid ethyl ester and 0.015 moles of primary aromatic, aliphatic or secondary aliphatic amine is refluxed for 4-7 hours in 8 ml of ethanol. Thereafter, the precipitate is filtered off, washed with water and recrystallized from ethanol. In some cases, purification by column chromatography is necessary (alumina / neutral, eluent: methylene chloride).

Nach dieser allgemeinen Vorschrift werden die in Tab. 1,2 und 3 zusammengefaßten Verbindungen (entsprechend Formel I) hergestellt:In accordance with this general procedure, the compounds summarized in Tables 1, 2 and 3 (corresponding to formula I) are prepared:

Tabelle 1Table 1

4-Arylamino-5,6-tetramethylenthieno/2,3-d/pyrimidin-2-ylcarbonsäureethylester4-arylamino-5,6-tetramethylenthieno / 2,3-d / pyrimidine-2-ylcarboxylate

R=R = Summento hum Molmol AusOut Schmelzenamel formelformula masseDimensions beubeu punktPoint te (%)te (%) (0C)( 0 C) C6H5 C 6 H 5 C19H19N3O2SC 19 H 19 N 3 O 2 S 353,4353.4 4949 157-159,5157 to 159.5 CeH4-o-CH3 CeH 4 -o-CH 3 C20H21N3O2SC 20 H 21 N 3 O 2 S 367,5367.5 3838 175-178175-178 C6H4-m-CH3 C 6 H 4 -m-CH 3 C20H21N3O2SC 20 H 21 N 3 O 2 S 367,5367.5 7575 146-149146-149 C6H4-p-CH3 C 6 H 4 -p-CH 3 C20H21N3O2SC 20 H 21 N 3 O 2 S 367,5367.5 7979 173-1.75173-1.75 C6H4-O-OCH3 C 6 H 4 -O-OCH 3 C20H21N3O3SC 20 H 21 N 3 O 3 S 383,5383.5 8383 234-237234-237 C6H4-m-OCH3 C 6 H 4 -m-OCH 3 C20H21N3O3SC 20 H 21 N 3 O 3 S 383,5383.5 7171 111-113111-113 C6H4-P-OCH3 C 6 H 4 -P-OCH 3 C20H21N3O3SC 20 H 21 N 3 O 3 S 383,5383.5 6969 170-171,5170 to 171.5 C6H4-P-COCH3 C 6 H 4 -P-COCH 3 C21H2IN3O3SC 21 H 2 IN 3 O 3 S 395,5395.5 5555 241-243241-243 C6H4-ITi-CIC 6 H 4 -ITi-CI C19H18CIN3O2SC 19 H 18 CIN 3 O 2 S 387,9387.9 6767 200-203200-203 C6H4-P-CIC 6 H 4 -P-CI C19H18CIN3O2SC 19 H 18 CIN 3 O 2 S 387,9387.9 6969 211-213211-213 C6H4-P-BrC 6 H 4 -P-Br C19H18BrN3O2SC 19 H 18 BrN 3 O 2 S 432,3432.3 3232 222-224222-224 C6H3-m-CI,p-CH3 C 6 H3-m-CI, p-CH 3 C20H20CIN3O2SC 20 H 20 CIN 3 O 2 S 401,9401.9 5050 119,5-121,5119.5 to 121.5 C6H4-P-FC 6 H 4 -PF C19H18FN3O2SC 19 H 18 FN 3 O 2 S 371,4371.4 3838 178,5-180178.5 to 180 C6H4-(Ti-CF3 C 6 H 4 - (Ti-CF 3 C20H18F3N3O2SC 20 H 18 F 3 N 3 O 2 S 421,4421.4 3131 181,5-183181.5 to 183 C6H3-ITi-CI,p-FC 6 H 3 -ITi-CI, pF C19H17CIFN3O2SC 19 H 17 CIFN 3 O 2 S 405,9405.9 6464 193-196193-196

Summento hum Molmol - Aus- Out -3- 237 663-3- 237 663 Tabelle 2Table 2 formelformula masseDimensions beubeu te (%)te (%) C17H17N3O2SC 17 H 17 N 3 O 2 S 327,4327.4 5353 Schmelzenamel C8H19N3O2SC 8 H 19 N 3 O 2 S 341,4341.4 1616 punktPoint C18H19N3O2SC 18 H 19 N 3 O 2 S 341,4341.4 4141 CC)CC) 4-Arylamino-5,6-dimethylthieno/2,3-d/pyrimiclin-2-ylcarbonsäureethylester4-arylamino-5,6-dimethylthieno / 2,3-d / pyrimiclin-2-ylcarboxylate C18H19N3O2SC 18 H 19 N 3 O 2 S 357,4357.4 5353 151-153151-153 R5 R 5 C18H19N3O3SC 18 H 19 N 3 O 3 S 357,4357.4 4545 146-149146-149 C18H19N3O3SC 18 H 19 N 3 O 3 S 357,4357.4 5353 176,5-178176.5 to 178 Ci9H19N3O3SCi 9 H 19 N 3 O 3 S 369,4369.4 2727 197,5-199197.5 to 199 C6H5 C 6 H 5 C18H18CiN3O2SC 18 H 18 CiN 3 O 2 S 375,9375.9 4343 126,5-128126.5 to 128 C6H4-ITi-CH3 C 6 H 4 -ITi-CH 3 C17H16FN3O2SC 17 H 16 FN 3 O 2 S 345,4345.4 4343 158-160158-160 C6H4-P-CH3C6H4-P-CH3 C18H16F3N3O2SC 18 H 16 F 3 N 3 O 2 S 395,4395.4 4545 194,5-195,5194.5 to 195.5 C6H4-O-OCH3 C 6 H 4 -O-OCH 3 C17H15CIFN3O2SC 17 H 15 CIFN 3 O 2 S 379,8379.8 4141 237,5^239237.5 ^ 239 C6H4-In-OCH3 C 6 H 4 -In-OCH 3 183,5-185183.5 to 185 C6H4-P-OCH3 C 6 H 4 -P-OCH 3 220-221220-221 C6H4-P-COCH3 C 6 H 4 -P-COCH 3 200,5-203200.5 to 203 C6H3-m-CI,P-CH3 C 6 H 3 -m-CI, P-CH 3 C6H4-P-FC 6 H 4 -PF C6H4-m-CF3 C 6 H 4 -m-CF 3 C6H5-m-CI,p-FC 6 H 5 -m-CI, pF

Tabelle 3Table 3

5,6-Disubstituierte4-Aminothieno/2,3-d/pyrimidin-2-ylcarbonsäureethylester5,6-Disubstituierte4-aminothieno / 2,3-d / pyrimidine-2-ylcarboxylate

NR4R5 NR 4 R 5

SummenformelMolecular formula

Molmassemolar mass

Ausbeu te (%)Payout (%)

Schmelzpunkt COMelting point CO

(CH2)4 (CH 2 ) 4 NHC10H17 NHC 10 H 17 (CH2)4 (CH 2 ) 4 NHC6H11 NHC 6 H 11 CH3CH3 CH 3 CH 3 NHC6H11 NHC 6 H 11 (CH2I4 (CH 2 I 4 N(C2H5J2 N (C 2 H 5 J 2 CH3CH3 CH 3 CH 3 N(C2H5),N (C 2 H 5 ), (CH2)4 (CH 2 ) 4 NC5H10 NC 5 H 10 CH3CH3 CH 3 CH 3 NC5H10 NC 5 H 10

C23H31N3O2S C19H25N3O2S C17H23N3O2S C17H23N3O2S C15H21N3O2S C18H23N3O2S C16H21N3O2SC 23 H 31 N 3 O 2 SC 19 H 25 N 3 O 2 SC 17 H 23 N 3 O 2 SC 17 H 23 N 3 O 2 SC 15 H 21 N 3 O 2 SC 18 H 23 N 3 O 2 SC 16 H 21 N 3 O 2 S

413,6 359,5 333,5 333,5 307,4 345,4 319,4413.6 359.5 333.5 333.5 307.4 345.4 319.4

125-127 155,5-157 127-129 101,5-102,5 70125-127 155.5-157 127-129 101.5-102.5 70

94,5-96 108,5-11094.5-96 108.5-110

Analog Beispiel 2 werden weiterhin hergestellt:Analogously to Example 2 are further prepared:

1,4-Bis-(2-ethoxycarbonyl-5,6-tetramethylenthieno/2,3-d/-pyrimidin-4-yl)-piperazin, C30H34N6O4S2 (606,8) Schmelzpunkt: 282-2850C, Ausbeute: 50%1,4-Bis (2-ethoxycarbonyl-5,6-tetramethylenethieno / 2,3-d / pyrimidin-4-yl) piperazine, C 30 H 34 N 6 O 4 S 2 (606.8) Melting point: 282-285 0 C, yield: 50%

1,4-Bis-(2-ethoxycarbonyl-5,6-dimethylthieno/2,3-d/pyrimidin-4-yl)-piperazin, C26H30N6O4S2 (554,7) Schmelzpunkt: 306-3070C, Ausbeute: 35%1,4-bis- (2-ethoxycarbonyl-5,6-dimethylthieno / 2,3-d / pyrimidin-4-yl) -piperazine, C 26 H 30 N 6 O 4 S 2 (554.7) Melting point: 306 -307 0 C, yield: 35%

Beispiel 3Example 3

^Furfurylamino-S.e-tetramethylenthieno^.S-d/pyrimidin^-ylcarbonsäurefurfurylamid, C21H20N4O3S (408,5) Ein Gemisch aus 0,005mol4-Chlor-5,6-tetramethylenthieno-/2,3-d/pyrimidin-2-ylcarborsäureethylester und 0,015 mol primäres aliphatisches Amin werden in 8ml Ethanol 8h unter Rückfluß gekocht. Die beim Abkühlen anfallenden Kristalle werden abgesaugt und mit warmen Wasser gewaschen. Die Reinigung des Produktes erfolgte durch Umkristallisieren aus Ethanol oder säulenchromatographisch (Aluminiumoxid/neutral, Elutionsmittel: Methylenchlorid).^ Furfurylamino-Se-tetramethylenethieno ^ .Sd / pyrimidin ^ -ylcarboxylic acid, ferurylamide, C21H20N4O3S (408.5) A mixture of 0.005mol 4-chloro-5,6-tetramethylenethieno / 2,3-d / pyrimidin-2-ylcarboxylic acid ethyl ester and 0.015 mol primary aliphatic amine are refluxed in 8 ml of ethanol for 8 hours. The crystals formed on cooling are filtered off with suction and washed with warm water. The product was purified by recrystallization from ethanol or by column chromatography (alumina / neutral, eluant: methylene chloride).

Analog werden hergestellt:Analog are produced:

4-Octylamino-5,6-tetramethylenthieno/2,3-d/pyrimidin-2-yl-carbonsäureoctyIamid,4-octylamino-5,6-tetramethylenthieno / 2,3-d / pyrimidin-2-yl-carbonsäureoctyIamid,

C27H44N4OS, (472,7)C 27 H 44 N 4 OS, (472,7)

Schmelzpunkt: 96-98°C, Ausbeute: 7%Melting point: 96-98 ° C, yield: 7%

4-Cyclohexylamino-5,6-dimethylthieno/2,3-d/pyrimidin-2-yl-carbonsäurecylohexylamid,4-cyclohexylamino-5,6-dimethylthieno / 2,3-d / pyrimidin-2-yl-carbonsäurecylohexylamid,

C21H30N4OS, (386,6)C 21 H 30 N 4 OS, (386,6)

Schmelzpunkt: 131-134X, Ausbeute: 9%Melting point: 131-134X, Yield: 9%

4-Octylamino-5,6-dimethylthieno/2,3-d/pyrimidin-2-yl-carbonsäureoctylamid, C25H42N4OS, (446,7)4-Octylamino-5,6-dimethylthieno / 2,3-d / pyrimidin-2-yl-carboxylic acid octylamide, C 25 H 42 N 4 OS, (446.7)

Schmelzpunkt: 65-700C, Ausbeute: 32%Melting point: 65-70 0 C, yield: 32%

Formelblattformula sheet

NR4R5 NR 4 R 5

Formel IFormula I

e\r2.e \ r 2 . alkyl, polyalkyl, poly methyl enmethyl ene ε3ε3 alkoxy, alkyl-alkoxy, alkyl amino, dialkyl-amino, dialkyl amino, acylaminoamino, acylamino E4-, S5 =E 4- , S 5 = H, alkyl, phenyl,H, alkyl, phenyl, substituiertessubstituted phenyl, aralkyl,phenyl, aralkyl, polymethylenpolymethylene

R1 R£ R 1 R £

Formel IIFormula II

COR5 COR 5

"= alkyl, polymethy-"= alkyl, polymethyl

len, · = alkoxylen, · = alkoxy

Cl R , E= alkyl, polymethy-Cl R, E = alkyl, polymethyl

len, S^ = alkoxylen, S ^ = alkoxy

Formel IIIFormula III

Claims (1)

Patentanspruch:Claim: Verfahren zur Herstellung von Thieno/2,3-d/pyrimidin-2-yl-carbonsäurederivaten der allgemeinen Formel I, worin R1, R2 = alkyl, polymethylen,Process for the preparation of thieno / 2,3-d / pyrimidin-2-yl-carboxylic acid derivatives of general formula I, wherein R 1 , R 2 = alkyl, polymethylene, R3 = alkoxy, alkylamino,dialkylamino, arylamino,R 3 = alkoxy, alkylamino, dialkylamino, arylamino, R4, R5 = H, alkyl, phenyl, substituiertes phenyl
bedeuten,R 4 , R 5 = H, alkyl, phenyl, substituted phenyl
mean, gekennzeichnet dadurch, daß 5,6-disubstituiertes 3,4-Dihydro-4-oxothieno/2,3-d/pyrimidin-2-ylcarbonsäureester der allgemeinen Formel II, worin R1, R2 und R3 obige Bedeutung besitzen, mit Phosphoroxidchlorid zu 5,6-disubstituierten 4-Chlorthieno/^S-d/pyrimidin^-ylcarbonsäureestem der allgemeinen Formel III, worin R1, R2 und R3 obige Bedeutung besitzen, umgesetzt und anschließend diese 4-Chlorderivate mit primären oder sekundären Aminen zur Reaktion gebracht werden. Hierzu 1 Seite Formelncharacterized in that 5,6-disubstituted 3,4-dihydro-4-oxothieno / 2,3-d / pyrimidin-2-ylcarboxylic ester of the general formula II, wherein R 1 , R 2 and R 3 have the above meaning, with phosphorus oxychloride to 5,6-disubstituted 4-Chlorthieno / ^ Sd / pyrimidin ^ -ylcarbonsäureestem of the general formula III, wherein R 1 , R 2 and R 3 have the above meaning, reacted and then reacted these 4-chloro derivatives with primary or secondary amines to the reaction become. For this 1 page formulas
DD27250785A 1985-01-11 1985-01-11 PROCESS FOR PREPARING 4-BASED SUBSTITUTED THIENO / 2,3-D / PYRIMIDIN-2-YLCARBONESAEUREDERIVATES DD237663A1 (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1167367A1 (en) * 1999-03-30 2002-01-02 Nippon Soda Co., Ltd. Thienopyrimidine compounds and salts thereof and process for the preparation of the same
WO2009104026A1 (en) * 2008-02-19 2009-08-27 Vichem Chemie Kutató Kft Tricyclic benzo[4,5]thieno-[2,3-d]pyrimidine-4-yl-amin derivatives, their salts, process for producing the compounds and their pharmaceutical use
EP2806875A4 (en) * 2012-01-25 2015-10-21 Proteostasis Therapeutics Inc Proteasome activity modulating compounds

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1167367A1 (en) * 1999-03-30 2002-01-02 Nippon Soda Co., Ltd. Thienopyrimidine compounds and salts thereof and process for the preparation of the same
EP1167367A4 (en) * 1999-03-30 2002-04-24 Nippon Soda Co Thienopyrimidine compounds and salts thereof and process for the preparation of the same
EP1323719A1 (en) * 1999-03-30 2003-07-02 Nippon Soda Co., Ltd. Thienopyrimidine compounds and salts thereof and process for the preparation of the same
WO2009104026A1 (en) * 2008-02-19 2009-08-27 Vichem Chemie Kutató Kft Tricyclic benzo[4,5]thieno-[2,3-d]pyrimidine-4-yl-amin derivatives, their salts, process for producing the compounds and their pharmaceutical use
US8802849B2 (en) 2008-02-19 2014-08-12 Vichem Chemie Kutató Kft. Tricyclic benzo[4,5]thieno-[2,3-d]pyrimidine-4-yl-amin derivatives, their salts, process for producing the compounds and their pharmaceutical use
EP2806875A4 (en) * 2012-01-25 2015-10-21 Proteostasis Therapeutics Inc Proteasome activity modulating compounds
AU2013202368B2 (en) * 2012-01-25 2016-06-16 Proteostasis Therapeutics, Inc. Proteasome activity modulating compounds
US9399647B2 (en) 2012-01-25 2016-07-26 Proteostasis Therapeutics, Inc. Proteasome activity modulating compounds

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