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US 8,940,880 B2Granted
Process for the preparation of 9-deoxo-9a-homoerythromycin A, modified in the C-4″ of the cladinose ring by an epoxide group
AssigneeNovartis AG
InventorsRafael Garcia, Oriol Martorell, Albert Codony
Life of this patent
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Abstract
The present invention concerns a process for the preparation of the compound of formula The compound of formula (1) is the key intermediate in the synthesis of some antibacterial agents of the triamilide class, such as Tulathromycin, useful to treat bacterial and protozoa infections.
Claims12
Process for the manufacture of a compound of formula
- comprising the steps of:
- (i) protecting the hydroxyl group in the C-2′ and, optionally, the C-9 oxime group of erythromycin A 9-(E)-oxime to obtain a compounds of formula
- wherein R1 is a hydroxyl protecting group and R2 is hydrogen or an oxime protecting group;
- (ii) oxidizing the compound of formula (3) in the presence of an oxidizing agent in order to obtain a compound of formula
- wherein R1 and R2 are as defined above;
- (iii) converting the compound of formula (4) to the corresponding epoxide of formula
- wherein R1 and R2 are each as defined above;
- (iv) removing the protecting group R1 and optionally R2 of the compound of formula (5) to yield the compound of formula
- (v) subjecting the oxime of formula (6) to a Beckmann rearrangement in order to obtain the corresponding 6,9-iminoether of formula
- and
- (vi) reducing the iminoether of formula (7) to obtain the epoxide of formula (1).
8 more elements
The process of clairnl, wherein the removal of the protecting group of R1 and optionally R2 is carried out by a treatment with a Ci-C4-alkanol.
A process for the manufacture of Tulathromycin, which comprises:
- (i) protecting the hydroxyl group in the C-2′ and, optionally, the C-9 oxime group of erythromycin A 9-(E)-oxime to obtain a compound of formula
- wherein R1 is a hydroxyl protecting group and R is hydrogen or an oxime protecting group;
- (ii) oxidizing the compound of formula (3) in the presence of an oxidizing agent in order to obtain a compound of formula
- wherein R1 and R are as defined above;
- (iii) converting the compound of formula (4) to the corresponding epoxide of formula
- wherein R1 and R are each as defined above;
- (iv) removing the protecting group R1 and optionally R2 of the compound of formula (5) to yield the compound of formula
- (v) reacting the compound of formula (1) with n-propylamine.
5 more elements
Dependencies are inferred from the claim text.