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Synthesis of tritium labeled MK‐886, a leukotriene biosynthesis inhibitor; employment of epibromohydrin as a masked electrophilic acetone synthon
Author(s) -
Schmidt Stanley J.,
Garnes Keith T.,
Heys J. Richard,
Landvatter Scott W.,
Adams Jerry L.
Publication year - 1991
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580290805
Subject(s) - chemistry , synthon , indole test , ketone , propanoic acid , electrophile , acetone , moiety , medicinal chemistry , tribromide , organic chemistry , stereochemistry , catalysis
1‐(4‐Chloro‐[3‐ 3 H]benzyl) ‐3‐( t ‐butylthio)‐ a , a ‐dimethyl‐5‐( i ‐propyl) ‐indole‐2‐propanoic acid ( 10 , MK‐886) was prepared by catalytic tritium/halogen exchange on 1‐(4‐chloro‐3‐iodobenzyl)‐3‐( t ‐butylthio)‐ a , a ‐dimethyl‐5‐( i ‐propyl)‐indole‐2‐propanoic acid ( 9 ). Compound 9 was prepared by a synthesis converging at the indole benzylation step. The required indole 4 was prepared by means of a Fischer indole synthesis employing the highly functionalized unsymmetrical ketone 3 . Ketone 3 was efficiently made in three steps using epibromohydrin as a masked electrophilic acetone synthon. The halogenated benzyl bromide moiety 7 was prepared in three steps from 1‐chloro‐2‐iodo‐4‐(trifluoromethyl)‐benzene.