Patent ID: 6872823
Filing Date: 2005-03-29
Classification: A61P,C07B,C07C,C07D,C12P,Y02P

Abstract:
1. A process for producing a compound represented by the following formula: which comprises comprising obtaining a compound represented by formula (VI-a) by any of the following Processes A to J: treating this compound with a boron trifluoride compound to thereby convert it into a boron chelate compound represented by the following formula: reacting this compound with 4-methylpiperazine to give a compound represented by the following formula: and then cleaving and eliminating the boron chelate of this compound: Process A: a process which comprises reacting a compound represented by formula (I): with a compound represented by formula (II-1-a) in the presence of a base: to give a compound represented by the formula (III-1-a): reducing this compound into a compound represented by formula (IV-a): reacting this compound with a compound represented by the following formula: to give a compound represented by the formula (V-a): and then treating this compound in the presence of a base; Process B: a process which comprises reacting a compound represented by formula (I): with a compound represented by formula (II-2-a) in the presence of a base: to give a compound represented by formula (III-2-a): eliminating the hydroxyl-protective group of this compound to give a compound represented by formula (IV-a): reacting this compound with a compound represented by the following formula: to give a compound represented by the formula (V-a): and then treating this compound in the presence of a base; Process C; a process which comprises reacting a compound represented by formula (I): with a compound represented by formula (II-1-a) in the presence of a base: to give a compound represented by formula (III-1-a): reducing this compound into a compound represented by formula (IV-a): treating this compound in the presence of a base to give a compound represented by the formula (VII-a): and reacting this compound with a compound represented by the following formula; Process D: a process which comprises reacting a compound represented by formula (1): with a compound represented by formula (II-2-a) in the presence of a base: to give a compound represented by formula (III-2-a): eliminating the hydroxyl-protective group of this compound to give a compound represented by formula (IV-a): treating this compound in the presence of a base to give a compound represented by formula (VII-a): and then reacting this compound with a compound represented by the following formula: Process E: a process which comprises reacting a compound represented by formula (I): with a compound represented by formula (II-1) in the presence of a base: to give a compound represented by formula (III-1): and then subjecting this compound to the following Method 1 or 2; Method 1: in case of the compound represented by the formula (III-1) where R Method 2: in case of the compound represented by the formula (III-1) where R3 is a hydrogen atom, a method which comprises optically resolving this compound by reacting with an optically active organic base; to obtain a carboxylic acid compound represented by the following formula: esterifying this compound in the presence of an alcohol represented by the following formula: to give an ester compound represented by the following formula: reducing the compound into a compound represented by formula (IV-a): reacting this compound with a compound represented by the following formula: to give a compound represented by formula (V-a): and then treating this compound in the presence of a base; Process F: a process which comprises reacting a compound represented by formula (I): with a compound represented by formula (II-1) in the presence of a base: to give a compound represented by formula (III-1): and then subjecting this compound to the following Method 1 or 2; Method 1: in case of the compound represented by the formula (III-1) where R Method 2: in case of the compound represented by the formula (III-1) where R to obtain a carboxylic acid compound represented by the following formula: esterifying this compound in the presence of an alcohol represented by the following formula: to give an ester compound represented by the following formula: reducing the compound into a compound represented by formula (IV-a): treating this compound in the presence of a base to give a compound represented by formula (VII-a): and then reacting this compound with a compound represented by the following formula; Process G: a process which comprises reacting a compound represented by the following formula: or by the following formula: with a compound represented by the following formula in the presence of a metal catalyst under a hydrogen gas atmosphere, optionally in the presence of a dehydrating agent or an acid: to give a compound represented by formula (III-1): and then subjecting this compound to the following Method 1 or 2; Method 1: in case of the compound represented by the formula (III-1) where R Method 2: in case of the compound represented by the formula (III-1) where R to obtain a carboxylic acid compound represented by the following formula: esterifying this compound in the presence of an alcohol represented by the following formula: to give an ester compound represented by the following formula: reducing the compound into a compound represented by formula (IV-a): reacting this compound with a compound represented by the following formula: to give a compound represented by the formula (V-a): and then treating this compound in the presence of a base; Process H: a process which comprises reacting a compound represented by the following formula: or by the following formula: with a compound represented by the following formula in the presence of a metal catalyst under a hydrogen gas atmosphere, optionally in the presence of a dehydrating agent or an acid: to give a compound represented by formula (III-1): and then subjecting this compound to the following Method 1 or 2; Method 1: in case of the compound represented by the formula (III-1) where R Method 2: in case of the compound represented by the formula (III-1) where R to obtain a carboxylic acid compound represented by the following formula: esterifying this compound in the presence of an alcohol represented by the following formula: to give an ester compound represented by the following formula: reducing the compound into a compound represented by formula (IV-a): treating this compound in the presence of abase to give a compound represented by formula (VII-a): and then reacting this compound with a compound represented by the following formula; Process I: a process which comprises reacting a compound represented by the following formula: with a compound represented by the following formula: to give a compound represented by the following formula: asymmetrically reducing this compound into a compound represented by formula (III-1-a): reducing this compound into a compound represented by formula (IV-a): reacting this compound with a compound represented by the following formula: to give a compound represented by the formula (V-a): and then treating this compound in the presence of a base; and Process J: a process which comprises reacting a compound represented by the following formula: with a compound represented by the following formula: to give a compound represented by the following formula: asymmetrically reducing this compound into a compound represented by formula (III-1-a): reducing this compound into a compound represented by formula (IV-a): treating this compound in the presence of a base to give a compound represented by formula (VII-a): and then reacting this compound with a compound represented by the following formula: in each of the above formulae, X 1 , X 2 and X 3 , each independently represents a halogen atom; R 1 represents a leaving group; R 3 represents a hydrogen atom or a carboxyl-protective group; R 4 represents a hydroxyl-protective group; R 5 and R 6 , each independently represents an alkyl group having 1 to 6 carbon atoms; R 7 represents a carboxyl-protective group; and Y represents an alkoxy group having 1 to 6 carbon atoms, a halogen atom or a dialkylamino group (wherein the alkyl groups may be the same or different and each represents an alkyl group having 1 to 6 carbon atoms).