Reaction equation
NC1C=C(N)C=C(N)C=1C1C=CC(C)=CC=1.[C:17]([O:20][CH:21]1[O:35][C@H:34]([CH2:36][O:37][C:38](=[O:40])[CH3:39])[C@@H:29]([O:30][C:31](=[O:33])[CH3:32])[C@H:24]([O:25][C:26](=[O:28])[CH3:27])[C@H:22]1[NH2:23])(=[O:19])[CH3:18].[I:41][C:42]1[C:47]([CH2:48][CH3:49])=[C:46]([I:50])[CH:45]=[C:44]([I:51])[C:43]=1[C:52]1[CH:57]=[CH:56][C:55]([C:58](Cl)=[O:59])=[C:54]([N+:61]([O-:63])=[O:62])[CH:53]=1>>[N+:61]([C:54]1[CH:53]=[C:52]([C:43]2[C:44]([I:51])=[CH:45][C:46]([I:50])=[C:47]([CH2:48][CH3:49])[C:42]=2[I:41])[CH:57]=[CH:56][C:55]=1[C:58]([C:21]1([O:35][C@H:34]([CH2:36][O:37][C:38](=[O:40])[CH3:39])[C@@H:29]([O:30][C:31](=[O:33])[CH3:32])[C@H:24]([O:25][C:26](=[O:28])[CH3:27])[C@H:22]1[NH2:23])[O:20][C:17](=[O:19])[CH3:18])=[O:59])([O-:63])=[O:62]Participants
Procedure
Freidel-Crafts acylation is performed on 2′,4′,6′-triiodo-3-nitrobiphenyl-4-carboxylic acid (6) in the presence of AlCl3 and CH3COCl to yield 2′,4′,6′-triiodo-3′-acetyl-3-nitrobiphenyl-4-carboxylic acid (12). C 13 H 6 I 3 N O 4 → C H 3 C O Cl Al Cl 3 C 15 H 8 I 3 N O 5 2′,4′,6′-triiodo-3′-acetyl-3-nitrobiphenyl-4-carboxylic acid (12) is then reacted with a zinc mercury amalgam and hydrochloric acid and heated to yield 2′,4′,6′-triiodo-3′-ethyl-3-nitrobiphenyl-4-carboxylic acid (13). C 15 H 8 I 3 N O 5 → Δ Zn ( Hg ) , H Cl C 15 H 10 I 3 N O 4 2′,4′,6′-triiodo-3′-ethyl-3-nitrobiphenyl-4-carboxylic acid (13) is reacted with thionyl chloride to yield 2′,4′,6′-triiodo-3′-ethyl-3-nitrobiphenyl-4-carbonyl chloride (14). C 15 H 10 I 3 N O 4 → S O Cl 2 C 15 H 9 Cl I 3 N O 3 1,3,4,6-tetra-O-acetyl-D-glucosamine (9) is reacted with 2′,4′,6′-triiodo-3′-ethyl-3-nitrobiphenyl-4-carbonyl chloride (14) to yield 2-nitro-4-(3′-ethyl-2′,4′,6′-triiodophenyl)-benzoyl-1,3,4,6-tetra-O-acetyl-D-glucosamine (15). C14H21NO9+C15H9ClI3NO3→C29H29I3N2O12 2-nitro-4-(3′-ethyl-2′,4′,6′-triiodophenyl)-benzoyl-1,3,4,6-tetra-O-acetyl-D-glucosamine (15) is treated with stannous chloride and hydrochloric acid to yield 2-amino-4-(3′-ethyl-2′,4′,6′-triiodophenyl)-benzoyl-D-glucosamine (16). C 29 H 29 I 3 N 2 O 12 → Sn Cl 2 , H Cl C 21 H 23 I 3 N 2 O 6 Example 2 is similar in general structure to Example 1, with the additional presence of a short alkyl chain attached to the radio-opaque tri-iodophenyl moiety at the C-3′ position to further increase lipophilicity of the molecule and enhance cell membrane permeability. The computed logP of Example 2 is 5.31.
Sources & evidence
- ORD record
- ord-af058d137c5048deb8f7eb97904b2b1c
- Source dataset
- uspto-grants-2005_08
- Patent number
- US06923950B2
Linked notes
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