Processes and intermediates for the preparation of heterocyclic sulfonamide compounds
AssigneeWyeth
InventorsAsaf Alimardanov, Antonia Nikitenko, Gregg Feigelson, John Potoski
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Abstract
Methods for preparing compound of formula (I) are described, wherein R1-R3 are defined herein, as are methods for preparing the intermediates formed therein. Also described are methods for enantioselectively preparing a chiral compound of the following structure, wherein R2 and R3 are defined herein.
Claims32
A method for preparing a sulfonamide compound of the structure:
- wherein:
- R1 is aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
- R2 and R3 are, independently, C1 to C6 alkyl, substituted C1 to C6 alkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
- said method selected from the group consisting of:
- (a) a method comprising:
- (i) enantioselectively hydrogenating R2C(═CHCOOH)R3 to R2CH(CH2COOH)R3;
- (ii) converting R2CH(CH2COOH)R3 to an imide of a chiral oxazolidinone;
- (iii) substituting the α-carbon atom of said imide of said chiral oxazolidinone with an azide;
- (iv) converting said imide of said chiral oxazolidinone containing said azide to an amine or salt thereof;
- (v) reducing said amine or salt thereof to an aminoalcohol or salt thereof;
- and
- (vi) sulfonylating said aminoalcohol or salt thereof;
- (b) a method comprising:
- (i) enantioselectively hydrogenating R2C(═CHCOOH)R3 to R2CH(CH2COOH)R3;
- (ii) converting R2CH(CH2COOH)R3 to an imide of a chiral oxazolidinone;
- (iii) substituting the α-carbon atom of said imide of a chiral oxazolidinone with an azide;
- (iv) converting said imide of a chiral oxazolidinone containing an azide to an imide of a chiral oxazolidinone containing an amine or salt thereof;
- (v) sulfonylating said imide of a chiral oxazolidinone containing an amine or salt thereof;
- and
- (vi) reducing said sulfonylated imide of a chiral oxazolidinone containing an amine or salt thereof;
- (c) a method comprising:
- (i) converting R2C(═CHCOOH)R3 to an unsaturated imide of a chiral oxazolidinone;
- (ii) diastereoselectively hydrogenating said unsaturated imide of a chiral oxazolidinone to an imide of a chiral oxazolidinone;
- (iii) substituting the α-carbon atom of said imide of said chiral oxazolidinone with an azide;
- (iv) converting said imide of said chiral oxazolidinone with said azide to an amine or salt thereof;
- (v) reducing said amine or salt thereof to an aminoalcohol or salt thereof;
- and
- (vi) sulfonylating said aminoalcohol or salt thereof;
- (d) a method comprising:
- (i) enantioselectively hydrogenating R2C(═CHCOOH)R3 to R2CH(CH2COOH)R3;
- (ii) converting R2CH(CH2COOH)R3 to an imide of a chiral oxazolidinone;
- (iii) substituting the α-carbon atom of said imide of said chiral oxazolidinone with an azide;
- (iv) converting said imide of said chiral oxazolidinone containing said azide to an aminoalcohol or salt thereof;
- and
- (v) sulfonylating said aminoalcohol or salt thereof;
- (e) a method comprising:
- (i) converting R2C(═CHCOOH)R3 to an unsaturated imide of a chiral oxazolidinone;
- (ii) diastereoselectively hydrogenating said unsaturated imide of a chiral oxazolidinone to an imide of a chiral oxazolidinone;
- (iii) substituting the α-carbon atom of said imide of said chiral oxazolidinone with an azide;
- (iv) converting said imide of said chiral oxazolidinone with said azide to an aminoalcohol or salt thereof;
- and
- (v) sulfonylating said aminoalcohol or salt thereof;
- and
- (f) a method comprising:
- (i) converting R2C(═CHCOOH)R3 to an unsaturated imide of a chiral oxazolidinone;
- (ii) diastereoselectively hydrogenating said unsaturated imide of a chiral oxazolidinone to an imide of a chiral oxazolidinone;
- (iii) substituting the α-carbon atom of said imide of a chiral oxazolidinone with an azide;
- (iv) converting said imide of a chiral oxazolidinone containing an azide to an imide of a chiral oxazolidinone containing an amine or salt thereof;
- (v) sulfonylating said imide of a chiral oxazolidinone containing an amine or salt thereof;
- and
- (vi) reducing said imide of a chiral oxazolidinone containing an amine or salt thereof.
A method for enantioselectively preparing a chiral compound, or derivative thereof, of the structure:
- wherein, R2 and R3 are, independently, C1 to C6 alkyl, substituted C1 to C6 alkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
- said method comprising:
- (i) converting R2C(═CHCOOH)R3 to a chiral oxazolidinone of the structure:
- wherein, R4 is C1 to C6 alkyl, substituted C1 to C6 alkyl, aryl, or substituted aryl;
- (ii) hydrogenating the product of step (i);
- and
- (iii) converting the product of step (ii) to said chiral compound.
A compound which is selected from the group consisting of (a) (S)-3-(3,5-difluorophenyl)-4,4,4-trifluorobutanoic acid, (b) (S)-4-Benzyl-3-((S)-3-(3,5-difluorophenyl)-4,4,4-trifluorobutanoyl)oxazolidin-2-one, (c) (S)-3-((2S,3R)-2-Azido-3-(3,5-difluorophenyl)-4,4,4-trifluorobutanoyl)-4-benzyloxazolidin-2-one, (d) (S)-3-((2S,3R)-2-Amino-3-(3,5-difluorophenyl)-4,4,4-trifluorobutanoyl)-4-benzyloxazolidin-2-one hydrochloride, (e) (2S,3R)-2-Amino-3-(3,5-difluorophenyl)-4,4,4-trifluorobutan-1-ol hydrochloride, and (f) N-((2S,3R)-1-((S)-4-Benzyl-2-oxo-oxazolidin-3-yl)-3-(3,5-difluorophenyl)-4,4,4-trifluoro-1-oxobutan-2-yl)-5-chlorothiophene-2-sulfonamide.
Dependencies are inferred from the claim text.