Photocleavable and acid cleavable linkers for combinatorial chemistry
AssigneePharmacopeia, Inc.
InventorsVinh D. Tran, Vu Van Ma, Ruiyan Liu
Life of this patent
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Abstract
A substrate for solid phase synthesis comprising a solid phase-linker combination of the formula I is disclosed. Also disclosed are processes for preparing the substrate and chemical intermediates useful therein. Among the novel intermediates are compounds of the formula II wherein R1 is —NO2 or —CHO; R2 is —OCH3, —CHO or —H; R3 is chosen from the group consisting of hydroxyl, the residue of a solid support having a plurality of amino groups, and the residue of an ester, and n=1 or 3. A substrate of solid phase synthesis of the formula III is also disclosed.
Claims5
A process for solid phase synthesis comprising:
- a) reacting a substrate for solid phase synthesis of the formula I:
- wherein:
- represents a solid support having a plurality of amino groups;
- R1 is —NO2;
- R2 is —CHO;
- and
- n=1 or 3,
- with an amine under conditions for reductive amination to provide a support-linked amine;
- b) carrying out a plurality of chemical transformations on said support-linked amine to provide a support-linked product;
- and
- c) exposing said support-linked product to ultraviolet light to cleave the product from the support and linker.
A process for solid phase synthesis comprising:
- a) reacting a substrate for solid phase synthesis of the formula I:
- wherein:
- represents a solid support having a plurality of amino groups;
- R1 is —CHO;
- R2 is —OCH3;
- and
- n=1 or 3,
- with an amine under conditions for reductive amination to provide a support-linked amine;
- b) carrying out a plurality of chemical transformations on said support-linked amine to provide a support-linked product;
- and
- c) reacting said support-linked product with acid to cleave the product from the support and linker.
A process for solid phase synthesis comprising:
- a) reacting a substrate for solid phase synthesis of the formula I:
- wherein:
- represents a solid support having a plurality of amino groups;
- R1 is —CHO;
- R2 is —H;
- and
- n=1 or 3,
- with an amine under conditions for reductive amination to provide a support-linked amine;
- b) carrying out a plurality of chemical transformations on said support-linked amine to provide a support-linked product;
- and
- c) reacting said support-linked product with an acid to cleave the product from the support and linker.
A process for solid phase synthesis comprising:
- a) reacting a substrate for solid phase synthesis of the formula III:
- wherein:
- represents a solid support having a plurality of amino groups;
- represents a first linker,
- represents a second linker in which R2=—OCH3,
- and n=1 or 3,
- with an amine under conditions for reductive amination to provide a support-linked amine;
- b) carrying out a plurality of chemical transformations on said support-linked amine to provide a support-linked product;
- c) exposing said support-linked product to ultraviolet light to cleave the product from the support and said first linker;
- and
- d) reacting said support-linked product with trifluoroacetic acid to cleave the support-linked product from the support and said second linker.
A process for solid phase synthesis comprising:
- a) reacting a substrate for solid phase synthesis of the formula III:
- wherein:
- represents a solid support having a plurality of amino groups;
- represents a first linker,
- represents a second linker in which R2=—H,
- and n=1 or 3,
- with an amine under conditions for reductive amination to provide a support-linked amine;
- b) carrying out a plurality of chemical transformations on said support-linked amine to provide a support-linked product;
- c) exposing said support-linked product to ultraviolet light to cleave the product from the support and said first linker;
- and
- d) reacting said support-linked product with trifluoroacetic acid to cleave the support-linked product from the support and said second linker.
Dependencies are inferred from the claim text.