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US 2019/0241525 A1Published application
Methods for the synthesis of deuterated dextromethorphan
AssigneeAvanir Pharmaceuticals
InventorsMatt Johnson, Cunxiang Zhao, Weihua Meng, Zhijun Lu, Yan Li
Life of this patent
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Abstract
The application describes methods for making a deuterated dextromethorphan of Formula (I), deuterated dextromethorphan produced by these methods, and pharmaceutically acceptable salts thereof.
Claims25
A method for synthesizing a deuterated dextromethorphan of Formula (I) or a pharmaceutically acceptable salt thereof
- the method comprising:
- (i) deuterating a dextromethorphan compound of Formula (II)
- to a compound of Formula (III)
- by N-demethylation followed by N-methylation in the presence of a base and iodomethane-D3 at a temperature in the range of −90° C. to 90° C. inclusive;
- and
- (ii) deuterating the compound of Formula (III) to the compound of Formula (I) by O-demethylation followed by O-methylation in the presence of a base and iodomethane-D3 at temperatures in the range of −10 to 10° C. inclusive.
3 more elements
(canceled)
A method for synthesizing a deuterated dextromethorphan of Formula (I)
- the method comprising:
- (i) N-demethylating the tertiary amine of a dextromethorphan compound of Formula (II)
- to obtain an N-demethylated compound of Formula (V)
- (ii) deuterating the N-demethylated compound of Formula (V) to a compound of Formula (Ill)
- by N-methylation in the presence of a base and iodomethane-D3 at a temperature in the range of −90° C. to 90° C. inclusive;
- (iii) O-demethylating the methoxy group of Formula (Ill) to a compound of Formula (VI)
- and
- (iv) deuterating the O-demethylated compound of Formula (VI) to the compound of Formula (I) by O-methylation in the presence of a base and iodomethane-D3 at temperatures in the range of −10° C. to 10° C. inclusive.
5 more elements
(canceled)
A method for synthesizing a deuterated dextromethorphan of Formula (I)
- the method comprising:
- (i) deuterating a dextromethorphan compound of Formula (II)
- to a compound of Formula (VII)
- by O-demethylation followed by O-methylation in the presence of a base and iodomethane-D3 at a temperature in the range of −10° C. to 10° C. inclusive;
- and
- (ii) deuterating the compound of Formula (VII) to the compound of Formula (I) by N-demethylation followed by N-methylation in the presence of a base and iodomethane-D3 at a temperature in the range of −90° C. to 90° C. inclusive.
3 more elements
(canceled)
A method for synthesizing a deuterated dextromethorphan of Formula (I)
- the method comprising:
- (i) O-demethylating the methoxy group of a dextromethorphan compound of Formula (II)
- to a compound of Formula (VIII)
- (ii) deuterating the O-demethylated compound of Formula (VIII) to a compound of Formula (VII)
- by O-methylation in the presence of a base and iodomethane-D3 at temperatures in the range of −10° C. to 10° C. inclusive;
- (iii) N-demethylating the tertiary amine of a dextromethorphan compound of Formula (VII) to a compound of Formula (IX);
- and
- (iv) deuterating the N-demethylated compound of Formula (IX) to the compound of Formula (I) by N-methylation in the presence of a base and iodomethane-D3 at a temperature in the range of −90° C. to 90° C. inclusive.
5 more elements
(canceled)
Dependencies are inferred from the claim text.