Synthesis of antibacterial aminoglycoside analogs
AssigneeCipla USA, Inc.
InventorsRaissa TREND, Michael DAPPEN, Christopher E. HENRY, Adam Aaron GOLDBLUM, James Bradley AGGEN, Ricardo Filipe de Jesus Gonçalves MENDONÇA, João Carlos Falcão SARDINHA
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Abstract
The present disclosure relates to novel methods for preparing antibacterial aminoglycoside compounds, as well as to related intermediates, and crystal forms thereof, useful in such methods.
Claims35
A process for preparing a compound of formula (2), or a salt thereof, or solvate thereof, or an enantiomer thereof, or a diastereomer thereof comprising:
- (a) contacting a compound of formula (1):
- or an enantiomer thereof, or a diastereomer thereof, with 1-{[(p-nitrobenzyl)oxy]carbonyl}-1H-benzotriazole (PNZ-Bt) to form the compound of formula (2):
- or a salt thereof, or a solvate thereof, or an enantiomer thereof, or a diastereomer thereof;
- wherein is a single bond or a double bond;
- R1 is H or C1-C3 alkyl;
- R2 is H or C1-C3 alkyl;
- and
- R3 is H or C1-C3 alkyl.
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7-10. (canceled)
13-16. (canceled)
18-19. (canceled)
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25-26. (canceled)
28-30. (canceled)
32-40. (canceled)
43-46. (canceled)
49-97. (canceled)
A compound selected from the group consisting of
- (i) a compound of formula (4):
- or a salt thereof, or a solvate thereof, or an enantiomer thereof, or a diastereomer thereof;
- (ii) a compound of formula (4a):
- or a salt thereof, or a solvate thereof;
- (iii) crystalline tert-butyl ((2S,3R)-2-(((1R,2S,3S,4R,6S)-6-((tert-butoxycarbonyl)amino)-4-((S)-4-((tert-butoxycarbonyl)amino)-2-hydroxybutanamido)-3-(((2R,3R,4R,5R)-3,5-dihydroxy-5-methyl-4-(methylamino)tetrahydro-2H-pyran-2-yl)oxy)-2-hydroxycyclohexyl)oxy)-6-(((((4-nitrobenzyl)oxy)carbonyl)amino)methyl)-3,4-dihydro-2H-pyran-3-yl)carbamate, Formula (4a), or a solvate thereof;
- (iv) crystalline tert-butyl ((2R,3R,4R,5R)-2-(((1S,2S,3R,4S,6R)-3-(((2S,3R)-6-(aminomethyl)-3-((tert-butoxycarbonyl)amino)-3,4-dihydro-2H-pyran-2-yl)oxy)-4-((tert-butoxycarbonyl)amino)-6-((S)-4-((tert-butoxycarbonyl)amino)-2-hydroxybutanamido)-2-hydroxycyclohexyl)oxy)-3,5-dihydroxy-5-methyltetrahydro-2H-pyran-4-yl)(methyl)carbamate, Formula (6a), or a solvate thereof;
- (v) a compound of formula (7):
- or a salt thereof, or solvate thereof, or an enantiomer thereof, or a diastereomer thereof;
- (vi) a compound of formula (7a):
- or a salt thereof, or a solvate thereof;
- and
- (vii) crystalline tert-butyl ((2R,3R,4R,5R)-2-(((1S,2S,3R,4S,6R)-4-((tert-butoxycarbonyl)amino)-6-((S)-4-((tert-butoxycarbonyl)amino)-2-hydroxybutanamido)-3-(((2S,3R)-3-((tert-butoxycarbonyl)amino)-6-(((2-hydroxyethyl)amino)methyl)-3,4-dihydro-2H-pyran-2-yl)oxy)-2-hydroxycyclohexyl)oxy)-3,5-dihydroxy-5-methyltetrahydro-2H-pyran-4-yl)(methyl)carbamate, Formula (7a), or a solvate thereof.
99-100. (canceled)
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104-107. (canceled)
Dependencies are inferred from the claim text.