Back to results
US 7,071,329 B2Granted
Process for preparing cephalosporins with salified intermediate
AssigneeACS DOBFAR S.p.A.
InventorsRiccardo Monguzzi, Antonio Manca, Leonardo Marsili, Maurizio Zenoni
Life of this patent
Estimating the term…
Abstract
Cephalosporins may be conveniently prepared by a process in which a benzathinium salt of formula (V) wherein: Z is benzathine; and X and R2 are as defined in the specification, is reacted with thiourea. The resulting product may be crystallized as a sodium salt, as an internal salt, or as a pharmaceutically acceptable salt.
Claims12
A process for preparing a compound of formula (I):
- wherein:
- R1 is H;
- and
- R2 is selected from the group consisting of
- —H, —CH3, —CH2OCH3, —CH2OCOCH3, and —CH═CH2,
- wherein said process comprises:
- (1) reacting a compound of formula (IV):
- wherein:
- X is Cl or Br;
- R2 is as defined above;
- and
- R3 is hydrogen,
- with benzathine or a salt thereof, to obtain crystals of a compound of formula (V):
- wherein:
- Z is benzathine;
- and
- X and R2 are as defined above;
- and
- (2) reacting said compound of formula (V) with thiourea, to obtain said compound of formula (I).
16 more elements
A compound of formula (V):
- wherein:
- Z is benzathine;
- X is Cl or Br;
- and
- R2 is selected from the group consisting of
- —H, —CH3, —CH2OCH3, —CH2OCOCH3, and —CH═CH2.
3 more elements
A process for preparing a compound of formula (V):
- wherein:
- Z is benzathine;
- X is Cl or Br;
- and
- R2 selected from the group consisting of
- —H, —CH3, —CH2OCH3, —CH2OCOCH3, and —CH═CH2,
- wherein said process comprises:
- (1) reacting a compound of formula (IV):
- wherein X and R2 are as defined above, and R3 is hydrogen, with benzathine or a salt thereof, to obtain said compound of formula (V).
6 more elements
A process for preparing a cephalosporin of formula (I) or a pharmaceutically acceptable salt thereof
- wherein:
- R1 is H or Na;
- and
- R2 is selected from the group consisting of
- —H, —CH3, —CH2OCH3, —CH2OCOCH3, and —CH═CH2;
- wherein said process comprises:
- (1) silylating a compound of formula (II):
- wherein R2 is as defined above, to obtain the corresponding trialkylsilyl-ester;
- (2) reacting said trialkylsilyl ester with a compound of formula (III):
- wherein X is Cl or Br and Y is Cl, or —O—CH═N+(CH3)2Cl−, to obtain a compound of formula (IV):
- wherein X and R2 are as defined above, and R3 is trialkylsilyl;
- (3) hydrolyzing said compound of formula (IV) at pH 7 to 7.5, to obtain a hydrolyzed compound;
- (4) reacting said hydrolyzed compound in an aqueous solution with benzathine or a salt thereof, to obtain a salt of formula (V):
- wherein Z is benzathine and R2 and X are as defined above, in which the carboxyl is salified by said benzathine;
- (5) collecting said salt of formula (V) by filtration, to obtain a solid;
- (6), washing said solid with water, to obtain a washed solid;
- and
- (7) reacting said washed solid in an aqueous solvent with thiourea, to obtain a solution of said compound of formula (I) in which R2 is as defined above and R1 is H, said compound of formula (I) being crystallized from this solution in the form of the sodium salt, of the salt of a pharmaceutically acceptable inorganic acid or of an internal salt.
15 more elements
Dependencies are inferred from the claim text.