Process for preparing dibenzothiazepine compounds
AssigneesAstraZeneca UK Limited, Ube Industries, Ltd.
InventorsPaul Michael Murray, Luis-Manuel Vaz, Debra Ainge, Katsumasa Harada, Shigeyoshi Nishino, Kiyotaka Yoshii
Life of this patent
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Abstract
A dibenzothiazepine compound is suitably prepared by subjecting a 2-amino-2′-carboxy-diphenylsulfide compound to dehydration-condensation reaction in the presence of an acidic catalyst; the 2-amino-2′-carboxy-diphenylsulfide compound is suitably prepared by reducing a 2-nitro-2′-carboxy-diphenylsulfide compound in a lower aliphatic ester solvent; and the 2-nitro-2′-carboxy-diphenylsulfide compound is suitably prepared by reacting a nitrobenzene compound with a thiosalicylic acid compound in a mixture of a lower aliphatic alcohol and water.
Claims17
A method of preparing a dibenzothiazepine compound of Formula I:
- in which each of R1, R2, R3, R4, R5, R6, R7, and R8, independently, represents a hydrogen atom, an alkyl group, an alkoxy group, an alkylcarbonyl group, an aryl group, an aryloxy group, or an arylcarbonyl group, each group being optionally substituted,
- which comprises steps of:
- reducing a 2-nitro-2′-carboxy-diphenylsulfide compound of Formula IV:
- in which each of R1, R2, R3, R4, R5, R6, R7 and R8 is the same as defined above, in an aliphatic ester of an aliphatic alcohol having 1 to 6 carbon atoms and an aliphatic carboxylic acid having 1 to 6 carbon atoms to obtain the 2-amino-2′-carboxy-diphenylsulfide compound of Formula V:
- and
- subjecting the 2-amino-2′-carboxy-diphenylsulfide compound of Formula V to dehydration-condensation reaction in the presence of an acidic catalyst.
A method of preparing a 2-amino-2′-carboxy-diphenylsulfide compound of Formula V:
- in which each of R1, R2, R3, R4, R5, R6, R7, and R8, independently, represents a hydrogen atom, an alkyl group, an alkoxy group, an alkylcarbonyl group, an aryl group, an aryloxy group, or an arylcarbonyl group, each group being optionally substituted,
- which comprises a step of reducing a 2-nitro-2′-carboxy-diphenylsulfide compound of Formula IV:
- in which each of R1,R2,R3,R4,R5,R6,R7,and R8 is the same as defined above, in an aliphatic ester of an aliphatic alcohol having 1 to 6 carbon atoms and an aliphatic carboxylic acid having 1 to 6 carbon atoms.
A method of preparing 2-nitro-2′-carboxy-diphenylsulfide compound of Formula IV:
- in which each of R1, R2, R3, R4, R5, R6, R7, and R8, independently, represents a hydrogen atom, an alkyl group, an alkoxy group, an alkylcarbonyl group, an aryl group, an aryloxy group, or an arylcarbonyl group, each group being optionally substituted,
- which comprises a step of reacting a nitrobenzene compound of Formula II:
- in which each of R1, R2, R3, and R4 is the same as defined above, with a thiosalicylic acid compound of Formula III:
- in which each of R5, R6, R7 and R8 is the same as defined above, in a mixture of an aliphatic alcohol having 1 to 6 carbon atoms and water.
Dependencies are inferred from the claim text.