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US 2004/0073045 A1Published application
Pyrrolidine derivative and process for producing the same
OwnerManabu Sasyou, Toyokazu Haga +3inventors
InventorsManabu Sasyou, Toyokazu Haga, Akio Kayano, Shigeto Negi, Hiroyuki Naka
Life of this patent
Estimating the term…
Abstract
A pyrrolidine derivative, which is an intermediate for a quinuclidine derivate side chain useful as a squalene synthase inhibitor, and producing method thereof are disclosed. A pyrrolidine derivative (X) represented by the following formula (X) (wherein R1 and R2 each represents a hydroxy group, C1-6 alkoxy groups or the like; R3 represents a hydrogen atom, a benzyl group or the like); or a salt thereof or a hydrate thereof: 1
Claims16
A compound represented by the general formula (X);
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- wherein each of R1 and R2 independently means a halogen atom, a hydroxyl group or a group represented by formula —O—R10 (wherein R10 means C1-6 alkyl groups which may have 1 to 3 substituents selected from a substituent group A consisting of a halogen atom, a hydroxyl group, a methoxy group, a phenyl group, C3-8 cycloalkyl groups and C1-6 alkoxy groups, or C3-8 cycloalkyl groups which may have 1 to 3 substituents selected from the substituent group A;
- and R3 means a benzyl group which may have 1 to 3 methoxy group(s) or nitro group(s) as substituent(s), or a hydrogen atom;
- with the proviso that a case (1) where R1 and R2 are the same with each other, and a case (2) where either of R1 and R2 is a hydroxyl group, and another is an ethoxy group or a chlorine atom are excluded);
- or a salt thereof or a hydrate thereof.
2 more elements
A compound represented by the general formula (X1);
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- wherein each of Z1, Z2, Z3 and Z4 independently means a hydrogen atom, a halogen atom, a hydroxyl group or a group represented by formula —O—R10 (wherein R10 means C1-6 alkyl groups which may have 1 to 3 substituents selected from a substituent group A consisting of a halogen atom, a hydroxyl group, a methoxy group, a phenyl group, C3-8 cycloalkyl groups and C1-6 alkoxy groups, or C3-8 cycloalkyl groups which may have 1 to 3 substituents selected from the substituent group A);
- any one of Z1 and Z2 as well as any one of Z3 and Z4 mean hydrogen atom;
- and R3 means benzyl group which may have 1 to 3 methoxy group(s) or nitro group(s) as substituent(s), or a hydrogen atom;
- with the proviso that a case (1) where a group which is not a hydrogen atom in Z1 and Z2 is the same with a group which is not a hydrogen atom in Z3 and Z4, and a case (2) where a group which is not a hydrogen atom in Z1 and Z2 is hydroxyl group, and a group which is not hydrogen atom in Z3 and Z4 is an ethoxy group or a chlorine atom are excluded;
- or a salt thereof or a hydrate thereof.
3 more elements
A process for producing 3-hydroxy-4-methoxypyrrolidine (6y) represented by the following formula (6y):
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- comprising the steps of:
- subjecting a compound (1y) represented by formula (1y) to oxidation reaction to obtain a compound (2y) represented by formula (2y);
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- then, converting two hydroxyl groups in said compound (2y) into leaving groups to obtain a compound (3y) represented by formula (3y) (wherein L1 means a halogen atom, a methylsulfonyloxy group, a p-toluenesulfonyloxy group, or a methanesulfonyloxy group);
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- then, allowing said compound (3y) to react with an amine derivative represented by general formula R3a—NH2 (wherein R3a means a benzyl group which may have 1 to 3 methoxy group(s) or nitro group(s) as substituent(s)) to obtain a compound (4y) represented by formula (4y) (wherein R3a has the same meaning as defined above);
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- then, allowing said compound (4y) to react with alkaline metal methoxide salt to obtain a compound (5y) represented by formula (5y) (wherein R3a has the same meaning as defined above);
- and
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- then, releasing R3a in said compound (5y);
- or a salt thereof or a hydrate thereof.
10 more elements
A process for producing 3-hydroxy-4-methoxypyrrolidine (6y) represented by the following formula (6y):
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- comprising the steps of:
- allowing a compound (4y) represented by formula (4y) (wherein R3a means a benzyl group which may have 1 to 3 methoxy group(s) or nitro group(s) as substituent(s)) to react with alkaline metal methoxide salt to obtain a compound (5y) represented by formula (5y) (wherein R3a has the same meaning as defined above);
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- and then, releasing R3a in said compound (5y);
- or a salt thereof or a hydrate thereof.
3 more elements
A process for producing 3-hydroxy-4-methoxypyrrolidine (8z) represented by formula (8z):
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- comprising the steps of:
- allowing a compound (1z) represented by the following formula (1z) (wherein R5 means C1-6 alkyl groups, a benzyl group or a hydrogen atom) to react with a compound represented by formula Ar—CHO (wherein Ar means a phenyl group which may have 1 to 3 substituent(s) selected from the group consisting of a nitro group and a methoxy group) to obtain a compound (2z) represented by formula (2z) (wherein each of Ar and R5 has the same meaning as defined above);
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- then, subjecting said compound (2z) to reductive reaction to obtain a compound (3z) represented by formula (3z) (wherein Ar has the same meaning as defined above);
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- then, converting hydroxyl groups in said compound (3z) into leaving groups to obtain a compound (4z) represented by formula (4z) (wherein Ar has the same meaning as defined above, and L1 means a halogen atom, a methanesulfonyloxy group, a p-toluenesulfonyl group or a trifluoromethylsulfonyloxy group);
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- then, subjecting said compound (4z) to reductive reaction to obtain a compound (5z) represented by formula (5z) (wherein each of Ar and L1 has the same meaning as defined above);
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- then, allowing said compound (5z) to react with a compound represented by formula R3a—NH2 (wherein R3a means a benzyl group which may have 1 to 3 methoxy group(s) or nitro group(s) as substituent(s)) to obtain a compound (6z) represented by formula (6z) (wherein each of Ar and R3a has the same meaning as defined above);
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- then, subjecting said compound (6z) to methylating reaction to obtain a compound (7z) represented by formula (7z) (wherein each of Ar and R3a has the same meaning as defined above);
- and
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- then, subjecting protecting group in said compound (7z) to deprotection;
- or a salt thereof or a hydrate thereof.
14 more elements
A process for producing 3-hydroxy-4-methoxypyrrolidine (8z) represented by formula (8z):
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- comprising the steps of:
- subjecting a compound (4z) represented by formula (4z) (wherein Ar means a phenyl group which may have 1 to 3 substituent(s) selected from the group consisting of a nitro group and a methoxy group, and L1 means a halogen atom, a methanesulfonyloxy group, a p-toluenesulfonyl group or a trifluoromethylsulfonyloxy group) to reductive reaction to obtain a compound (5z) represented by formula (5z) (wherein each of Ar and L1 has the same meaning as defined above);
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- then, allowing said compound (5z) to react with formula R3a—NH2 (wherein R3a means a benzyl group which may have 1 to 3 methoxy group(s) or nitro group(s) as substituent(s)) to obtain a compound (6z) represented by formula (6z) (wherein each of Ar and R3a has the same meaning as defined above);
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- then, subjecting said compound (6z) to methylating reaction to obtain a compound (7z) represented by formula (7z) (wherein each of Ar and R3a has the same meaning as defined above);
- and
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- then, subjecting protecting group in said compound (7z) to deprotection;
- or a salt thereof, or a hydrate thereof.
9 more elements
Dependencies are inferred from the claim text.