- PROCESS FOR MAKING ANAGRELIDE
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The invention relates to a process for the manufacture and purification of pharmaceutically active compound anagrelide of formula (1). The process is based on converting anagrelide or an acid addition salt thereof to a formate salt of anagrelide, in particular to anagrelide hemiformate.
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Page/Page column 11
(2015/01/16)
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- PROCESS FOR MAKING ANAGRELIDE
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The present invention relates to an improved process for making anagrelide of formula (1), or an acid addition salt thereof, including any hydrated or solvated form thereof, comprising reacting a compound of formula (3), or an acid addition salt thereof, (3), wherein R is a C1-C4 alkyl group, with chloroformamidine hydrochloride of formula (8), in an inert solvent, followed by treatment of the reaction mixture with a base.
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Page/Page column 12
(2014/09/29)
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- Process for the Manufacture of Anagrelide Hydrochloride Monohydrate
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The present invention relates to a process for preparation of Anagrelide Hydrochloride Monohydrate.
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Page/Page column 2; 4
(2010/12/29)
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- PROCESS FOR THE PREPARATION OF ETHYL-N-(2, 3-DICHLORO-6-NITROBENZYL) GLYCINE HYDROCHLORIDE
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The invention relates to a process for the preparation of anagrelide, and for the preparation of intermediates for use in preparing anagrelide. The invention also relates to the inte?nediates per se, in particular compounds of formula (V) where R constitutes a suitable leaving group, which may not be hydrogen. The R group may be is selected from: (i) -SiR1 3, (ii) -CH2Ar, (iii) -COOR2, and (iv) sulfonates such as -SO2R3.
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Page/Page column 14
(2008/12/08)
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- METHOD FOR THE PRODUCTION OF ANAGRELIDE HYDROCHLORIDE
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Disclosed is a method for producing 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazoline-2(3H)-on hydrochloride (anagrelide hydrochloride). Said method comprises the following steps: a) 2,3-dichlorobenzaldehyde is nitrated to obtain 2,3-dichloro-6-nitrobenzaldehyde; b) 2,3-dichloro-6-nitrobenzaldehyde is reacted with hydroxylamine HCl and acetic anhydride by applying heat so as to obtain 2,3-dichloro-6-nitrobenzonitrile; c) the nitro group of 2,3-dichloro-6-nitrobenzonitrile is reduced to obtain 2,3-dichloro-6-aminobenzonitrile; d) the nitrile group of 2,3-dichloro-6-aminobenzonitrile is reduced to obtain 2,3-dichloro-6-aminobenzylamine dihydrochloride; e) 2,3-dichloro-6-aminobenzylamine dihydrochloride is reacted with i) bromoacetic acid ethyl ester, CH3CN, and triethylamine; and ii) BrCN to obtain (2-amino-5,6-dichloro-4H-quinazoline-3-yl) acetic acid ethyl ester; f) (2-amino-5,6-dichloro-4H-quinazoline-3-yl) acetic acid ethyl ester is reacted in cycloalkylation conditions to obtain 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazoline-2(3H)-on; and g) 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazoline-2(3H)-on is reacted with HCl to obtain anagrelide hydrochloride.
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Page/Page column 5-6
(2010/02/13)
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- USE OF 2-AMINO-2H-QUINAZOLINE DERIVATIVES FOR PRODUCING THERAPEUTIC AGENTS
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The invention relates to the use of 2-amino-2H-quinazoline derivatives of general chemical formula (I), wherein R1 represents an alkyl group having 1 - 5 carbon atoms and R2, R3, R4 and R5 independently represent a chlorine or hydrogen atom, in addition to the pharmaceutically compatible salts thereof for producing therapeutic agents for treating myeloproliferative diseases, high blood pressure and bronchodilation.
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Page/Page column 13
(2010/02/07)
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- Method for the manufacture of anagrelide
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Methods are provided for making Anagrelide base from 2,3-dichlorobenzaldehyde. A method is also provided for making an intermediate compound ethyl N-(2,3-dichloro-6-nitrobenzyl)glycine from 2,3-dichlorobenzaldehyde and for reducing the glycine compound using either SnCl2 or a specially defined catalyst. A cyclization method to form Anagrelide base from the corresponding iminoquinazoline compound is further provided.
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- Process for the preparation of 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazolin-2[3H]-one
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This invention relates to a new and improved process for the preparation of 6,7-dichloro-1,5-dihydroimidazo[2,1-b]-quinazolin-2[3H]-one of formula STR1 (anagrelide), a valuable blood platelet antiaggregative compound. According to the process of the invention the compound of formula (I) is prepared by subjecting a new 2-cyanoiminoquinazoline derivative of the general formula STR2 wherein R stands for cyano or a group of the formula COOR1, in the latter R1 representing lower alkyl optionally carrying a phenyl substituent, to thermal cyclization in an acidic medium. The invention also relates to new 2-cyanoiminoquinazo-lines of the general formula (III) used for the production of anagrelide and to the preparation of the said compounds. The invention provides an advantageous process for the preparation of anagrelide which is devoid of the drawbacks of the hitherto known processes and renders possible the production of the compound of the formula (I) on industrial scale, too.
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- Process for and 2-(cyanoimino)-quinazoline derivatives useful as intermediates in the preparation of 6,7-di-(chloro)-1,5-di(hydro)-imidazo-[2,1-b]quinazolin-2[3H]-one and process for preparing the 2-(cyanoimino)-quinazoline derivatives
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A subject matter of the invention is a process for the preparation of 6,7-di-(chloro)-1,5-di-(hydro)-imidazo[2,1-b]quinazolin-2[3H]-one of formula or a salt thereof including their hydrates, characterized by subjecting [2-(cyanoimino)-5,6-di-(chloro)-1,2,3,4-tetra-(hydro)-quinazolin-3-yl]-acetonitrile or a /2-(cyanoimino)-5,6-di-(chloro)-1,2,3,4-tetra-(hydro)-quinazolin-3-yl/-acetic acid alkylester of the general formula wherein R'stands for a cyano group or a group of the formula in which latter R1represents a straight or branched alkyl group having from 1 to 6 carbon atom(s), optionally carrying a phenyl substituent, to thermic cyclization in an acidic medium. Further subject matters of the invention are [2-(cyanoimino)-5,6-di-(chloro)-1,2,3,4-tetra-(hydro)-quinazolin-3-yl]-acetonitriles or -acetic acid alkylesters of the general formula wherein R' is as defined above, useful as intermediates in the said process and a process for preparing them.
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- Optionally substituted 1,2,3,5-tetrahydroimidezo(2,1-b)-quinazolin-2-ones and 6(H)-1,2,3,4-tetrahydropyimido(2,1-b)quinazolin-2-ones
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Optionally substituted 1,2,3,5-tetrahydroimidazol[2,1-b]-quinazolin-2-ones and 6-[H]-1,2,3,4-tetrahydropyrimidol[2,1-b]quinazolin-2-ones or the pharmaceutically acceptable salts thereof are compounds useful as blood platelet anti-aggregative and/or antihypertensive and/or bronchodilator agents in mammals, including humans.
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- Process for the preparation of imidazo[2,1-b]quinazolinones
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Known cardiovascular agents of the formula STR1 wherein R1 and R2 are each independently hydrogen, (lower)alkyl, (lower)alkoxy, (lower)alkylthio, trifluoromethyl, hydroxy, nitro, chloro, bromo or fluoro are prepared by reacting a compound of the formula STR2 in which R1 and R2 are as described above and R3 is hydrogen, (lower)alkyl or aryl, with a compound of the formula STR3 in which X is a leaving group as described herein.
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- Alkyl 5,6-dichloro-3,4-dihydro-2(1H)-iminoquinazoline-3-acetate hydrohalides
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The known blood platelet antiaggregative agent 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-one is prepared in high yield via an improved process involving a novel intermediate of the Formula STR1 in which R1 is (lower)alkyl and X is bromo, chloro or iodo. Two processes for the preparation of compounds of the Formula III are disclosed, one of which involves the novel intermediate STR2
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- Optionally substituted 1,2,3,5-tetrahydroimidezo(2,1-b)-quinazolin-2-ones and 6(H)-1,2,3,4-tetrahydropyimido(2,1-b)quinazolin-2-ones
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Optionally substituted 1,2,3,5-tetrahydroimidazo[2,1-b]-quinazolin-2-ones and 6-[H]-1,2,3,4-tetrahydropyrimido[2,1-b]-quinazolin-2-ones or the pharmaceutically acceptable salts thereof are compounds useful as blood platelet anti-aggregative and/or antihypertensive and/or bronchodilator agents in mammals, including humans.
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