US 6,307,048 B1Granted

Enantioselective alkylation of tricyclic compounds

AssigneeSchering Corporation

InventorsShen-Chun Kuo, Charles F. Bernard, Frank Xing Chen, Donald Hou, Agnes S. Kim-Meade, George G. Wu

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Abstract

Disclosed is a process for preparing a compound of the formula: wherein X1, X2, X3, X4, and X5 are independently selected from the group consisting of H, halo, alkyl, alkoxy, aryl, and aryloxy, and R is a protecting group, in which a compound having the formula wherein X1, X2, X3, X4, and X5 are as defined above, is treated with the following, in any sequence: (a) a non-nucleophilic strong base; (b) a chiral amino alcohol; and (c) a compound having the formula wherein L is a leaving group and R is as defined above. The compounds made by this process are useful intermediates for preparing compounds that are inhibitors of farnesyl protein transferase.

Claims17

Dependent claims

A process for preparing a compound of the formula:

wherein X1, X2, X3, X4, and X5 are independently selected from the group consisting of H, halo, alkyl, aryl, and aryloxy, and R is a protecting group, said process comprising:
treating a compound having the formula
wherein X1, X2, X3, X4, and X5 are a defined above, with the following, in any sequence:
(a) a non-nucleophilic strong base;
(b) a chiral amino alcohol, wherein the chiral amino alcohol is a compound
(i) having the formula
wherein the dotted line represents an optional second bond and wherein R1 is selected from alkoxy, aryloxy, or NRARB, wherein RA and RB are selected from alkyl or aryl, R1 being optionally substituted by one or more alkoxy groups,
(ii) having the formula
wherein R2 is a phenyl group optionally substituted by 1 to 5 substituents independently selected from the group consisting of alkyl and alkoxy, or
(iii) having the formula
and
(c) a compound having the formula
wherein L is a leaving group selected from the group consisting of sulfonates, phosphates, benzoates, and halo, and R is as defined above.

10 more elements

A process for preparing a compound having the formula

wherein X1, X2, X3, X4, and X5 are independently selected from the group consisting of H, halo, alkyl, aryl, and aryloxy, and R is a protecting group, said process comprising:
(a) reacting a compound having the formula
wherein X1, X2, X3, X4, and X5 are as defined above, with a non-nucleophilic strong base in the presence of a chiral amino alcohol to form a complex;
wherein the chiral amino alcohol is a compound
(i) having the formula
wherein the dotted line represents an optional second bond and wherein R1 is selected from alkoxy, aryloxy, or NRARB, wherein RA and RB are selected from alkyl or aryl, R1 being optionally substituted by one or more alkoxy groups,
(ii) having the formula
wherein R2 is a phenyl group optionally substituted by 1 to 5 substituents independently selected from the group consisting of alkyl and alkoxy, or
(iii) having the formula
(b) reacting the complex formed in step (a) with a compound having the formula
wherein L is a leaving group selected from the group consisting of sulfonates, phosphates, benzoates, and halo, and R is as defined above.

8 more elements

Dependencies are inferred from the claim text.

Facts

Application: 09/442,511Filed 18 Nov 1999 · us provisional application
Priority: 20 Nov 1998
Granted: 23 Oct 2001
Term ends: Not estimatedThe source records don’t support an estimate.

Classification5 codes

C07D 401/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
Y02P 20/55
Improvements relating to the production of bulk chemicals: design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
C07D
Heterocyclic compounds