Processes for preparing functionalized cyclooctenes
AssigneesTambo, Inc., The Research Foundation of State University of New York
InventorsJose M. Mejia Oneto, Nathan Yee, Jochem Theodoor Van Herpt, Chun-Min Zeng, Da-Ming Gou, Maksim Royzen
Life of this patent
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Abstract
The present disclosure relates to processes for preparing functionalized cyclooctenes and the synthetic intermediates prepared thereby.
Claims48
A process of preparing a compound of formula I, or a salt thereof:
- wherein
- R1 is selected from the group consisting of —OR4, optionally substituted heterocyclyl, and an amino acid moiety;
- n is 0, 1, 2, 3 or 4;
- each R2 is independently C1-4alkyl, C1-4haloalkyl, and C1-4alkoxy;
- and
- D is a payload moiety;
- R4 is hydrogen or C1-4 alkyl;
- comprising contacting a compound of formula II:
- with HO—R4, an optionally substituted heterocyclyl or an amino acid moiety, or a salt thereof, and a compound of formula III:
- wherein each R3 is independently C1-4 alkyl, in an organic solvent in the presence of a base.
A process of preparing a compound of formula X, or a salt thereof:
- wherein
- R1 is selected from the group consisting of —OR4, an optionally substituted heterocyclyl, and an amino acid moiety;
- n is 0, 1, 2, 3 or 4;
- each R2 is independently C1-4alkyl, C1-4haloalkyl, and C1-4alkoxy;
- and
- R4 is hydrogen or C1-4alkyl;
- comprising contacting a compound of formula IV:
- with HO—R4, an optionally substituted heterocyclyl or an amino acid, or a salt thereof, and a compound of formula III:
- wherein each R3 is independently C1-4 alkyl, in an organic solvent in the presence of a base.
A process of preparing a compound of formula I, or a salt thereof:
- wherein
- R1 is selected from the group consisting of —OR4, optionally substituted heterocyclyl, and an amino acid moiety;
- n is 0, 1, 2, 3 or 4;
- each R2 is independently C1-4 alkyl, C1-4 haloalkyl, and C1-4 alkoxy;
- D is a payload moiety;
- and
- R4 is hydrogen or C1-4 alkyl;
- comprising contacting a compound of formula X, or a salt thereof:
- with a payload moiety, or a salt thereof, in an organic solvent in the presence of a base.
A process of preparing a composition comprising a compound of formula IV, or a salt thereof:
- wherein
- n is 0, 1, 2, 3, or 4;
- and
- each R2 independently hydrogen or C1-4 alkyl;
- comprising contacting one equivalent of a compound of formula V, or a salt thereof:
- with 3-5 equivalents of N,N′-disuccinimidylcarbonate in 15-25 volumes of an anhydrous organic solvent in the presence of a base at a temperature from 15-30° C. for 5-10 hours.
A process for resolving a composition comprising one or more stereoisomers of a compound of formula VI, or a salt thereof:
- wherein
- n is 0, 1, 2, 3, or 4;
- each R2 is independently C1-4 alkyl, C1-4 haloalkyl, and C1-4 alkoxy;
- comprising the steps of:
- (a) contacting a composition comprising one or more stereoisomers of formula VI with a chiral base to provide a chiral salt of the compound of formula VI;
- (b) cooling the composition of step (a);
- (c) isolating the chiral salt of the compound of formula VI;
- and
- (d) hydrolyzing the chiral salt of the compound of formula VI to provide the enantiomerically enriched composition comprising a compound of formula VI, or a salt thereof.
A process for the preparation of an enantiomerically enriched composition comprising a compound of formula VII, or a salt thereof:
- wherein
- n is 0, 1, 2, 3 or 4;
- each R2 is independently C1-4 alkyl, C1-4 haloalkyl, and C1-4 alkoxy;
- and
- R4 is independently hydrogen or C1-4 alkyl;
- comprising sequentially contacting an enantiomerically enriched composition of a compound of formula VI, or a salt thereof:
- with:
- (i) a solution comprising KI and I2, (ii) a base, and (iii) a hydrolyzing composition comprising a base and a compound of formula R4—OH, to provide the enantiomerically enriched composition of a compound of formula VII, or a salt thereof.
A process for the preparation of an enantiomerically enriched composition comprising a compound of formula VIIB, or a salt thereof:
- wherein R5 is hydrogen or C1-4 alkyl, comprising hydrolyzing an enantiomerically enriched composition of a compound of formula IXB, or a salt thereof:
- with a hydrolyzing composition comprising a base and a compound of formula R4—OH, to provide the enantiomerically enriched composition of a compound of formula VIIB, or a salt thereof.
A process for resolving a composition comprising one or more stereoisomers of a compound of formula VIIA, or a salt thereof:
- wherein
- R5 is hydrogen or C1-4 alkyl, comprising the steps of:
- (a) contacting a composition comprising one or more stereoisomers of formula VIIA with a chiral base to provide a chiral salt of the compound of formula VIIA;
- (b) cooling the composition of step (a);
- (c) isolating the chiral salt of the compound of formula VIIA;
- and
- (d) hydrolyzing the chiral salt of the compound of formula VIIA to provide the enantiomerically enriched composition comprising a compound of formula VIIA, or a salt thereof.
A process for the preparation of an enantiomerically enriched composition comprising a compound of formula IXB, or a salt thereof:
- wherein R5 is hydrogen or C1-4 alkyl, comprising contacting an enantiomerically enriched composition of a compound of formula VIIIB, or a salt thereof:
- with a base to provide the enantiomerically enriched composition of a compound of formula IXB, or a salt thereof.
A process for the preparation of an enantiomerically enriched composition comprising a compound of formula VIIIB, or a salt thereof:
- wherein R5 is hydrogen or C1-4alkyl, comprising contacting an enantiomerically enriched composition of a compound of formula VIB, or a salt thereof:
- with a solution comprising KI and I2 to provide the enantiomerically enriched composition of a compound of formula VIIIB, or a salt thereof.
A process for the preparation of an enantiomerically enriched composition comprising a compound of formula VIIB, or a salt thereof:
- wherein
- R4 is hydrogen or C1-4 alkyl;
- and
- R5 is hydrogen or C1-4 alkyl;
- comprising the steps of:
- (a) contacting an enantiomerically enriched composition of a compound of formula VIB, or a salt thereof:
- with a solution comprising KI and I2 to provide an enantiomerically enriched composition of a compound of formula VIIIB, or a salt thereof:
- (b) contacting the enantiomerically enriched composition of a compound of formula VIIIB with a base to provide an enantiomerically enriched composition of a compound of formula IXB, or a salt thereof:
- (c) hydrolyzing the enantiomerically enriched composition of a compound of formula IXB, or a salt thereof, with a hydrolyzing composition comprising a base and a compound of formula R4—OH, to provide the enantiomerically enriched composition of a compound of formula VIIB, or a salt thereof.
A process for the preparation of an enantiomerically enriched composition comprising a compound of formula VB, or a salt thereof:
- wherein
- R4 is hydrogen or C1-4 alkyl;
- and
- R5 is hydrogen or C1-4 alkyl;
- comprising isomerizing an enantiomerically enriched composition of a compound of formula VIIB, or a salt thereof:
A process for the preparation of an enantiomerically enriched composition comprising a compound of formula IVB, or a salt thereof:
- wherein R5 is hydrogen or C1-4alkyl, comprising contacting an enantiomerically enriched composition of a compound of formula VB, or a salt thereof:
- with N,N′-disuccinimidyl carbonate (DSC) under conditions to provide the enantiomerically enriched composition comprising a compound of formula IVB.
The process of any preceding claim, wherein R2 or R5 is methyl.
An enantiomerically enriched composition comprising a compound selected from Table 1, or a salt thereof:
- TABLE 1
- IVC
- IVD
- IVE
- VC-1
- VD-1
- VE-1
- VIC
- VID
- VIE
- VIIC
- VIID
- VIIE
- VIIIC
- VIIID
- VIIIE
- IXC
- IXD
- IXE
- XC
- XD
- XE
The process of any preceding claim, wherein the enantiomerically enriched composition has a % ee of greater than about 25%, or about 50%, or about 70%, or about 80%, or about 90%, or about 95%, or about 98%, or about 99% or about 100%.
Dependencies are inferred from the claim text.