Synthesis of tritium labeled MK-886, a leukotriene biosynthesis inhibitor; employment of epibromohydrin as a masked electrophilic acetone synthon
✍ Scribed by Stanley J. Schmidt; Keith T. Garnes; J. Richard Heys; Scott W. Landvatter; Jerry L. Adams
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- French
- Weight
- 404 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0022-2135
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✦ Synopsis
Abstract
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.