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US 12,497,375 B2Granted
Processes and intermediates for the preparations of benzoprostacyclin analogues and benzoprostacyclin analogues prepared therefrom
AssigneeChirogate International Inc.
InventorsChun-Yu Lin, Tzyh-Mann Wei, Shih-Yi Wei
Life of this patent
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Abstract
The invention relates to processes for preparing benzoprostacyclin analogues and intermediates prepared from the process, and the benzoprostacyclin analogues prepared therefrom. The invention also relates to cyclopentenone intermediates in racemic or optically active form.
Claims2
A process for preparing an optically enriched compound of Formula 4a:
- wherein P is H, P1 or P2;
- X is Cl, Br, I, or —CH2CH2CH2COOR1, wherein R1 is C1-7-alkyl or C7-11-aralkyl;
- and P1 and P2 are protective groups for the hydroxyl groups, the process comprising the steps of:
- (1′) reacting an optically enriched compound of Formula (R)-1a′:
- wherein P1 and X are as defined above, with a cuprate derived from an optically enriched compound of Formula L1a, Formula L2a, or Formula L3a:
- wherein Y is Cl, Br, or I;
- and P2 is as defined above, to form a compound of Formula 2a:
- wherein P and X are as defined above;
- (2′) reducing a ketone of the compound of Formula 2a to form a compound of Formula 3a:
- wherein P and X are as defined above;
- (3′) performing an intramolecular cyclization of the compound of Formula 3a to form the compound of Formula 4a:
- wherein P and X are as defined above;
- (4′) optionally performing a deprotecting reaction to remove the protective groups for the hydroxyl groups;
- and
- (5′) optionally performing a Suzuki cross-coupling reaction of the compound of Formula 2a, 3a or 4a wherein X is Cl, Br, or I, to form the compound of Formula 2a, 3a or 4a wherein X is —CH2CH2CH2COOR1 and R1 is as defined above.
12 more elements
A process for preparing a racemic compound of Formula 4b:
- wherein P is H, P1 or P2;
- X is Cl, Br, I, or —CH2CH2CH2COOR1, wherein R1 is C1-7-alkyl or C7-11-aralkyl;
- and P1 and P2 are protective groups for the hydroxyl groups, the process comprising the steps of:
- (1″) reacting a racemic compound of Formula 1′:
- wherein P1 and X are as defined above, with a cuprate derived from a racemic and diastereomeric mixture comprising a compound of Formula L1b, Formula L2b, or Formula L3b:
- wherein X1 is Cl, Br, or I;
- and P2 is as defined above, to form a compound of Formula 2b:
- wherein P and X are as defined above;
- (2″) reducing a ketone of the compound of Formula 2b to form a compound of Formula 3b:
- wherein P and X are as defined above;
- (3″) performing an intramolecular cyclization of the compound of Formula 3b to form the compound of Formula 4b:
- wherein P and X are as defined above;
- (4″) optionally performing a deprotecting reaction to remove the protective groups for the hydroxyl groups;
- and
- (5″) optionally performing a Suzuki cross-coupling reaction of the compound of Formula 2b, 3b or 4b when X is Cl, Br, or I, to form the compound of Formula 2b, 3b or 4b wherein X is —CH2CH2CH2COOR1 and R1 is as defined above.
12 more elements
Dependencies are inferred from the claim text.