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US 6,784,210 B2Granted
Compound and a novel process for their preparation
AssigneeAstraZeneca AB
InventorsKeith Fagnou, Mark Lautens
Life of this patent
Estimating the term…
Abstract
The present invention is directed to a procedure for making an enantiomerically enriched compound containing a hydronaphthalene ring structure. The process involves reacting oxabenzonorbornadienes with nucleophiles using rhodium as a catalyst and in the presence of a phosphine ligand. The compounds synthesized may be used in pharmaceutical preparations for the treatment of a variety of diseases and conditions.
Claims16
A compound according to formula IV:
- wherein:
- a) R8 is H or CH3;
- b) t=0-3
- c) R9 is a C3-C6 aryl optionally substituted at one or more positions with a group selected from:
- a C1-C3 alkyl;
- a C1-C3 alkoxy;
- Cl;
- F;
- NO2;
- and CF3;
- d) X and Y are independently selected from the group consisting of H;
- NH2;
- F;
- Cl;
- Br;
- a C1-C3 alkyl;
- and a C1-C3 alkoxy;
- or wherein the combination XY or YY together form a C3-C6 carbocyclic ring or a C3-C6 heterocyclic ring containing one or more heteroatoms selected from the group consisting of O;
- N;
- and S;
- e) Z is selected from O or NRa, wherein Ra is selected from:
- (i) a straight or branched C1-C6 alkyl;
- (ii) phenyl;
- (iii) (O)C—O—Rb, wherein Rb is a straight or branched C1-C6 alkyl;
- (iv) —SO2—Rc, wherein Rc is an unsubstituted phenyl or a phenyl substituted with a C1-C3 alkyl or NO2;
- and
- (v) —SO2—(CH2)q—Si(CH3)3 wherein q is 1-3;
- and with the proviso that when Z is O, R10 is H;
- when Z is NRa, R10 is either H or CH3;
- and with the further proviso that when Z is O and R10 is H, t is 2 or 3 and either X or Y is not H.
27 more elements
A compound selected from the group consisting of:
- (1S,2S)-N-(1-hydroxyl-1,2-dihydro-naphthalen-2-yl)-benzene sulfonamide;
- (1R,2R)-2-(methyl-phenyl-amino)-1,2-dihydro-naphthalen-1-ol;
- (1R*,2R*)-2-benzylamino-1,2-dihydro-naphthalen-1-ol;
- (1R*,2R* )-2-(4-methoxy-benzylamino)-1,2-dihydro-naphthalen-1-ol;
- (1R,2S)-2-methoxy-N-phenyl-1,2-dihydro-1-naphthalenamine;
- tert-butyl(1R,2S)-2-methoxy-1,2-dihydro-1-naphthalenylcarbamate;
- N-[(1R,2S)-2-methoxy-1,2-dihydro-1-naphthalenyl]-2-(trimethylsilyl) ethanesulfonamide;
- N-[(1R,2S)-2-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl]-4-methylbenzenesulfonamide;
- N-[(1R,2S)-2-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl]-4-methylbenzenesulfonamide;
- 4-methyl-N-[(1R,2S)-2-phenoxy-1,2,3,4-tetrahydro-1-naphthalenyl]benzenesulfonamide;
- (1R,2S)-1-{[(4-methylphenyl)sulfonyl]amino}-1,2,3,4-tetrahydro-2-naphthalenyl acetate;
- (1R,2S)-1-{[(4-methylphenyl)sulfonyl]amino}-1,2-dihydro-2-naphthalenyl benzoate;
- (1R,2S)-1-{[(4-methylphenyl)sulfonyl]amino}-1,2-dihydro-2-naphthalenyl pivalate;
- N-[(1R,2S)-2-methoxy-1,2-dihydro-1-naphthalenyl]-2-(trimethylsilyl) ethanesulfonamide, and
- tert-butyl(1R,2S)-2-methoxy-1,2-dihydro-1-naphthalenylcarbamate.
12 more elements
A pharmaceutical composition comprising a compound according to formula IV:
- wherein:
- a) R8 is H or CH3;
- b) t=0-3
- c) R9 is a C3-C6 aryl optionally substituted at one or more positions with a group selected from:
- a C1--C3 alkyl;
- a C1-C3 alkoxy;
- Cl;
- F;
- NO2;
- and CF3;
- d) X and Y are independently selected from the group consisting of H;
- NH2;
- F;
- Cl;
- Br;
- a C1-C3 alkyl;
- and a C1-C3 alkoxy;
- or wherein the combination XY or YY together form a C3-C6 carbocyclic ring or a C3-C6 heterocyclic ring containing one or more heteroatoms selected from the group consisting of O;
- N;
- and S;
- e) Z is selected from O or NRa, wherein Ra is selected from:
- (i) a straight or branched C1-C6 alkyl;
- (ii) phenyl;
- (iii) (O)C—O—Rb, wherein Rb is a straight or branched C1-C6 alkyl;
- (iv) —SO2—Rc, wherein Rc is an unsubstituted phenyl or a phenyl substituted with a C1-C3 alkyl or NO2;
- and
- (v) —SO—(CH2)q—Si(CH3)3 wherein q is 1-3;
- and
- when Z is O, R10 is H;
- when Z is NRa;
- R10 is either H or CH3.
28 more elements
A process for preparing a compound of formula IV:
- wherein:
- a) R8 is H or CH3;
- b) t=0-3
- c) R9 is a C3-C6 aryl optionally substituted at one or more positions with a group selected from:
- a C1-C3 alkyl;
- a C1-C3 alkoxy;
- Cl;
- F;
- NO2;
- and CF3;
- d) X and Y are independently selected from the group consisting of H;
- NH2;
- F;
- Cl;
- Br;
- a C1-C3 alkyl;
- and a C1-C3 alkoxy;
- or wherein the combination XY or YY together form a C3-C6 carbocyclic ring or a C3-C6 heterocyclic ring containing one or more heteroatoms selected from the group consisting of O;
- N;
- and S;
- e) Z is selected from O or NRa wherein Ra is selected from:
- (i) a straight or branched C1-C6 alkyl;
- (ii) phenyl;
- (iii) (O)C—O—Rb wherein Rb is a straight or branched C1-C6 alkyl;
- (iv) —SO2—Rc wherein Rc is an unsubstituted phenyl or a phenyl substituted with a C1-C3 alkyl or NO2;
- and
- (v) —SO2—(CH2)q—Si(CH3)3 wherein a is 1-3;
- and
- when Z is O, R10 is H;
- when Z is NRa, R10 is either H or CH;
- comprising reacting a compound of formula R9—(CH2)tNHR8 with a compound of formula V
- wherein R8, R9, t, X, Y, and Z are as defined above and wherein said reaction is catalyzed by [Rh(COD)Cl]2 in the presence of a phosphine ligand.
29 more elements
Dependencies are inferred from the claim text.