Back to results
US 10,759,764 B2Granted
Fluorination of organic compounds
AssigneePresident and Fellows of Harvard College
InventorsTobias Ritter, Constanze Nicole Neumann
Life of this patent
Estimating the term…
Abstract
Methods for fluorinating organic compounds utilizing a novel organic reagent are described herein. The invention further discloses the utility of this reagent for incorporation of the 18 F isotope into hydroxyl group-containing organic molecules for PET imaging studies. Preparation of the reagents is described along with isolable intermediate structures from reaction of the reagent with a hydroxyl group-containing organic molecule.
Claims30
A compound of Formula (I):
- wherein
- D is oxygen;
- A is hydrogen, LiX, MgX2, ScX3, ScR63YX3, YR63, BR63, BX3, TiX4, TiR64, ZrX4, ZrR64, FeX3, FeR63, ZnX2, ZnR62, AlX3, AlR63, InX3, InR63, SiX4, SiR64, SnX2, SnR62, SnX4, SnR64, BiX3, or BiR63;
- each occurrence of R6 is independently C1-6 alkyl, —OR7, C6-10 aryl, C6-10 aralkyl, 5-10 membered heteroaryl, 5-10 membered heteroaralkyl, 4-10 membered heterocyclyl, 4-10 membered heterocyclylalkyl, 3-10 membered carbocyclyl, or 3-10 membered carbocyclylalkyl, wherein each of C1-6 alkyl, C6-10 aryl, C6-10 aralkyl, 5-10 membered heteroaryl, 5-10 membered heteroaralkyl, 4-10 membered heterocyclyl, 4-10 membered heterocyclylalkyl, 3-10 membered carbocyclyl, and 3-10 membered carbocyclylalkyl is independently optionally substituted with 0 to 5 occurrences of R5;
- each occurrence of X is independently halogen or Q−t;
- Q−t is an anion;
- R1 and R2 are independently selected from the group consisting of C1-6 alkyl, C6-10 aryl, C6-10 aralkyl, 5-10 membered heteroaryl, 5-10 membered heteroaralkyl, 4-10 membered heterocyclyl, 4-10 membered heterocyclylalkyl, 3-10 membered carbocyclyl, and 3-10 membered carbocyclylalkyl, each of which is independently optionally substituted with 0 to 5 occurrences of R5;
- R3 and R4 are independently selected from the group consisting of hydrogen, unsubstituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, nitro, cyano, halo, C1-6 haloalkyl, C1-6 alkoxy, optionally substituted C6-10 aryl, optionally substituted C6-10 aralkyl, optionally substituted 5-10 membered heteroaryl, optionally substituted 4-10 membered heterocyclyl, optionally substituted 3-10 membered carbocyclyl, optionally substituted 4-10 membered heterocyclylalkyl, acyl, —NH2, —NHR7, —N(R7)2, —OH, —SH, —SO2R7, —SOR7, —SO2N(R7)2, and —SR7;
- each occurrence of R7 is independently selected from the group consisting of hydrogen, acyl, optionally substituted aliphatic, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R7 groups are taken together with their intervening atoms to form an optionally substituted heterocyclic ring;
- each occurrence of R5 is independently selected from the group consisting of halo, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkoxy, optionally substituted C6-10 aryl, optionally substituted 5-10 membered heteroaryl, optionally substituted 4-10 membered heterocyclyl, optionally substituted 3-10 membered carbocyclyl, nitro, cyano, acyl, —NH2, —NHR7, —N(R7)2, —OH, —SH, —SO2R7, —SOR7, —SO2N(R7)2, and —SR7;
- t is the anion charge number and is 1, 2, or 3;
- v is 0, 1, 2, or 3;
- and
- m is 1, 2, 3, 4, or 5;
- provided that the compound is electrically neutral.
12 more elements
A compound of Formula (II) or (II′):
- wherein:
- S is an organic substrate;
- Q⊖ is Cl−, Br−, or NO3−;
- Q2⊖ is SO42−;
- R1 and R2 are independently selected from the group consisting of C1-6 alkyl, C6-10 aryl, C6-10 aralkyl, 5-10 membered heteroaryl, 5-10 membered heteroaralkyl, 4-10 membered heterocyclyl, 4-10 membered heterocyclylalkyl, 3-10 membered carbocyclyl, and 3-10 membered carbocyclylalkyl, each of which is independently optionally substituted with 0 to 5 occurrences of R5;
- R3 and R4 are independently selected from the group consisting of hydrogen, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, nitro, cyano, halo, C1-6 haloalkyl, C1-6 alkoxy, optionally substituted C6-10 aryl, optionally substituted C6-10 aralkyl, optionally substituted 5-10 membered heteroaryl, optionally substituted 4-10 membered heterocyclyl, optionally substituted 3-10 membered carbocyclyl, optionally substituted 4-10 membered heterocyclylalkyl, acyl, —NH2, —NHR7, —N(R7)2, —OH, —SH, —SO2R7, —SOR7, —SO2N(R7)2, and —SR7;
- each occurrence of R7 is independently selected from the group consisting of hydrogen, acyl, optionally substituted aliphatic, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R7 groups are taken together with their intervening atoms to form an optionally substituted heterocyclic ring;
- and
- each occurrence of R5 is independently selected from the group consisting of halo, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkoxy, optionally substituted C6-10 aryl, optionally substituted 5-10 membered heteroaryl, optionally substituted 4-10 membered heterocyclyl, optionally substituted 3-10 membered carbocyclyl, nitro, cyano, acyl, —NH2, —NHR7, —N(R7)2, —OH, —SH, —SO2R7, —SOR7, —SO2N(R7)2, and —SR7.
6 more elements
A compound of Formula (V):
- wherein:
- S is an organic substrate;
- R1 and R2 are independently selected from the group consisting of C1-6 alkyl, C6-10 aryl, C6-10 aralkyl, 5-10 membered heteroaryl, 5-10 membered heteroaralkyl, 4-10 membered heterocyclyl, 4-10 membered heterocyclylalkyl, 3-10 membered carbocyclyl, and 3-10 membered carbocyclylalkyl, each of which is independently optionally substituted with 0 to 5 occurrences of R5;
- R3 and R4 are independently selected from the group consisting of hydrogen, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, nitro, cyano, halo, C1-6 haloalkyl, C1-6 alkoxy, optionally substituted C6-10 aryl, optionally substituted C6-10 aralkyl, optionally substituted 5-10 membered heteroaryl, optionally substituted 4-10 membered heterocyclyl, optionally substituted 3-10 membered carbocyclyl, optionally substituted 4-10 membered heterocyclylalkyl, acyl, —NH2, —NHR7, —N(R7)2, —OH, —SH, —SO2R7, —SOR7, —SO2N(R7)2, and —SR7;
- each occurrence of R7 is independently selected from the group consisting of hydrogen, acyl, optionally substituted aliphatic, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or two R7 groups are taken together with their intervening atoms to form an optionally substituted heterocyclic ring;
- and
- R5 is independently selected from the group consisting of halo, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkoxy, optionally substituted C6-10 aryl, optionally substituted 5-10 membered heteroaryl, optionally substituted 4-10 membered heterocyclyl, optionally substituted 3-10 membered carbocyclyl, nitro, cyano, acyl, —NH2, —NHR7, —N(R7)2, —OH, —SH, —SO2R7, —SOR7, —SO2N(R7)2, and —SR7.
4 more elements
Dependencies are inferred from the claim text.