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US 2023/0286920 A1Published application
Cyclooctynes for click chemistry
AssigneeMassachusetts Institute of Technology
InventorsRonald T. Raines, Brian Gold, Jesús M. Dones, Nile S. Abularrage, Brian James Graham
Life of this patent
Estimating the term…
Abstract
Provided herein are dibenzocyclooctyne compounds useful as reagents in 1,3-dipolar cycloaddition reactions, and methods for their preparation.
Claims26
A compound of formula (I):
- or a pharmaceutically acceptable salt thereof,
- wherein:
- R1 and R2 are, independently for each occurrence, F, Cl, Br, I, OTf, B(OH)2, CN, NHR5, NHS(O)2R5, OR5, OS(O)2R5, SR5, —CF3, —C(O)OC1-6 alkyl, —C(O)N(C1-6 alkyl)2, —C(O)R5, S(O)2R5, NO2, —C1-6 alkyl, —C1-6 alkenyl, or 5- to 10-membered heteroaryl substituted with 1, 2, 3, 4, or 5 R6 groups, optionally wherein the alkyl and alkenyl are substituted with one or more R5 groups;
- R3 and R4 are, independently for each occurrence, H or —C1-6 alkyl;
- R5 is selected from H, —C1-6-alkyl, —CF3, —C(O)OC1-6 alkyl, or —C(O)N(C1-6 alkyl)2;
- R6 is selected from H, F, Cl, Br, I, OTf, CN, NH2, OR5, SR5, —CF3;
- —C(O)R5, —C(O)OC1-6 alkyl, NO2, or —C1-6 alkyl;
- n is 0, 1, or 2;
- p is 0, 1, or 2;
- X1 is N or CH;
- and
- X2 is N+ or C;
- provided that when X1 is N, X2 is C;
- or when X1 is CH, X2 is N+.
11 more elements
A process of making a compound of formula (II):
- or a pharmaceutically accepted salt thereof,
- wherein:
- R1 and R2 are, independently for each occurrence, F, Cl, Br, I, OTf, B(OH)2, CN, NHR5, NHS(O)2R5, OR5, OS(O)2R5, SR5, —CF3, —C(O)OC1-6 alkyl, —C(O)N(C1-6 alkyl)2, —C(O)R5, S(O)2R5, NO2, —C1-6 alkyl, —C1-6 alkenyl, or 5- to 10-membered heteroaryl substituted with 1, 2, 3, 4, or 5 R6 groups, optionally wherein the alkyl and alkenyl are substituted with one or more R5 group;
- R3 and R4 are, independently for each occurrence, H or —C1-6 alkyl;
- R5 is selected from H, —C1-6-alkyl, —CF3;
- —C(O)OC1-6 alkyl, or —C(O)N(C1-6 alkyl)2;
- R6 is selected from H, F, Cl, Br, I, OTf, CN, NH2, OR5, SR5, —CF3, —C(O)R5, —C(O)OC1-6 alkyl, NO2, —C1-6 alkyl;
- n is 0, 1, or 2;
- p is 0, 1, or 2;
- and
- X is CH or N;
- wherein the process comprises:
- (A) combining a compound of formula (III):
- with a compound of formula (IV):
- and a non-nucleophilic base to provide the compound of formula (V):
- and
- (B) combining the compound of formula (V) with a carbodiimide to provide the compound of formula (II).
14 more elements
A process of making a compound of formula (VIa):
- or regioisomer thereof,
- wherein:
- R1 and R2 are, independently for each occurrence, F, Cl, Br, I, OTf, B(OH)2, CN, NHR5, NHS(O)2R5, OR5, OS(O)2R5, SR5, —CF3, —C(O)OC1-6 alkyl, —C(O)N(C1-6 alkyl)2, —C(O)R5, S(O)2R5, NO2, —C1-6 alkyl, —C1-6 alkenyl, or 5- to 10-membered heteroaryl substituted with 1, 2, 3, 4, or 5 R6 groups, optionally wherein the alkyl and alkenyl are substituted with one or more R5 groups;
- R3 and R4 are, independently for each occurrence, H or —C1-6 alkyl;
- R5 is selected from H, —C1-6-alkyl, —CF3;
- —C(O)OC1-6 alkyl, or —C(O)N(C1-6 alkyl)2;
- R6 is selected from H, F, Cl, Br, I, OTf, CN, NH2, OR5, SR5, —CF3, —C(O)R5, —C(O)OC1-6 alkyl, NO2, —C1-6 alkyl;
- R7 is C1-6 alkyl optionally substituted with one or more C6-10 aryl or 5- to 10-membered heteroaryl;
- n is 0, 1, or 2;
- p is 0, 1, or 2;
- X is CH or N;
- and
- Y is O or NH;
- wherein the process comprises combining a compound of formula (II):
- with a compound of formula (VIIa):
- to provide the compound of formula (VIa).
13 more elements
A process of making a compound of formula (VIb):
- or a regioisomer thereof,
- wherein:
- R1 and R2 are, independently for each occurrence, F, Cl, Br, I, OTf, B(OH)2, CN, NHR5, NHS(O)2R5, OR5, OS(O)2R5, SR5, —CF3, —C(O)OC1-6 alkyl, —C(O)N(C1-6 alkyl)2, —C(O)R5, S(O)2R5, NO2, —C1-6 alkyl, —C1-6 alkenyl, or 5- to 10-membered heteroaryl substituted with 1, 2, 3, 4, or 5 R6 groups, wherein the alkyl and alkenyl are optionally substituted with one or more R5 groups;
- R3 and R4 are, independently for each occurrence, H or —C1-6 alkyl;
- R5 is selected from H, —C1-6-alkyl, —CF3;
- —C(O)OC1-6 alkyl, or —C(O)N(C1-6 alkyl)2;
- R6 is selected from H, F, Cl, Br, I, OTf, CN, NH2, OR5, SR5, —CF3, —C(O)R5, —C(O)OC1-6 alkyl, NO2, —C1-6 alkyl;
- R7 is C1-6 alkyl optionally substituted with one or more C6-10 aryl or 5- to 10-membered heteroaryl;
- n is 0, 1, or 2;
- p is 0, 1, or 2;
- X is CH or N;
- and
- Y is O or NH;
- wherein the process comprises combining a compound of formula (II):
- with a compound of formula (VIIb):
- to provide the compound of formula (VIb).
13 more elements
Dependencies are inferred from the claim text.