Synthesis of 14C-labeled 4-hydroxyindole as an intermediate for the preparation of (S)-2-[4-[2-[3-(indol-2-[14C]-4-yloxy)-2-hydroxypropylamino]-2-methylpropyl]-phenoxy]pyridine-5-carboxamide (LY368842-[indole-14C]) glycolate

Synthesis of 4-hydroxyindole labeled with 14C at the 2-position was accomplished based on the vicarious nucleophilic substitution reaction of benzyl-protected 3-nitrophenol with p-chlorophenoxyacetonitrile-[1-14C]. This was followed by the reductive cyclization of o-nitrocyanomethyl derivative by palladium catalyzed hydrogenation. p-Chlorophenoxyacetonitrile-[1-14C] was prepared from commercially available p-chlorophenoxymethyl chloride and sodium cyanide-[14C]. 4-Hydroxyindole-[2-14C] was used for the synthesis of 14C-labeled β3 adrenergic agonist LY368842. Copyright © 2002 John Wiley & Sons, Ltd.

[1]  G. McGaughey,et al.  New generation dopaminergic agents. 6. Structure-activity relationship studies of a series of 4-(aminoethoxy)indole and 4-(aminoethoxy)indolone derivatives based on the newly discovered 3-hydroxyphenoxyethylamine D2 template. , 1999, Journal of medicinal chemistry.

[2]  K. Hashimoto,et al.  H-D EXCHANGE OF PSILOCIN AND ITS ANALOGS , 1999 .

[3]  B. Czeskis.  Synthesis of(S)-1-(1H-indol-4-yloxy)-3-[4-(3-methoxyphenyl)-4-hydroxypiperidin-1-yl)-propan-2-ol (LY333068) succinate, and its 3-[14C]-isotopomer based on chiral glycerol-[14C] derivatives , 1998 .

[4]  Björn C. G. Söderberg,et al.  Palladium-Catalyzed Synthesis of Indoles by Reductive N-Heteroannulation of 2-Nitrostyrenes , 1997 .

[5]  K. Ryan,et al.  Synthesis and reactivity of pyrrolo[3,2-e]indole: Removal of a N-BOM group from an unactivated indole , 1997 .

[6]  J. Marino,et al.  An Improved Synthesis of 3-Methyl-5-hydroxy Protected Indoles , 1994 .

[7]  Yoichi M. A. Yamada,et al.  Syntheses of (S)-(−)-pindolol and [3′-13C]-(R)-(−)-pindolol utilizing a lanthanum-lithium-(R)-BINOL ((R)-LLB) catalyzed nitroaldol reaction , 1994 .

[8]  Hideo Tanaka,et al.  A facile synthesis of 4-hydroxy- and 4-aminoindoles through corresponding indolines , 1989 .

[9]  K. Wojciechowski,et al.  Reactions of organic anions, 147. Simple and general synthesis of hydroxy‐ and methoxyindoles via vicarious nucleophilic substitution of hydrogen , 1988 .

[10]  A. F. Renaldo,et al.  Palladium-catalyzed coupling of 2-bromoanilines with vinylstannanes. A regiocontrolled synthesis of substituted indoles , 1988 .

[11]  J. Pitha,et al.  Affinity labels for beta-adrenoceptors: preparation and properties of alkylating beta-blockers derived from indole. , 1987, Journal of medicinal chemistry.

[12]  A. Kalir,et al.  One-Step Synthesis of 2- and 4-Nitrobenzyl Cyanides , 1987 .

[13]  D. Brunswick,et al.  Synthesis and beta-adrenergic receptor blocking potency of 1-(substituted amino)-3-(4-indolyloxy)propan-2-ols. , 1986, Journal of medicinal chemistry.

[14]  M. Mąkosza,et al.  Reactions of organic anions. Part 110. Vicarious nucleophilic substitution of hydrogen in nitroarenes with .alpha.-substituted nitriles and esters. Direct .alpha.-cyanoalkylation and .alpha.-carbalkoxyalkylation of nitroarenes , 1984 .

[15]  M. Mąkosza,et al.  Vicarious nucleophilic substitution of hydrogen in nitroarenes with α-substituted nitriles and esters. Direct α-cyanoalkylation and α-carbalkoxyalkylation of nitroarenes , 1984 .

[16]  D. B. Repke,et al.  Psilocin analogs. III. Synthesis of 5‐methoxy‐ and 5‐hydroxy‐1,2,3,4‐tetrahydro‐9H‐pyrido[3,4‐b]indoles , 1982 .

[17]  A. Rashidbaigi,et al.  Synthesis and characterization of iodoazidobenzylpindolol. , 1982, Journal of pharmaceutical sciences.

[18]  M. Somei,et al.  The Chemistry of Indoles. XVI. A Convenient Synthesis of Substituted Indoles carrying a Hydroxy Group, a Halogeno Group, or a Carbon Side Chain at the 4-Position via 4-Indolediazonium Salts and a Total Synthesis of (±)-6,7-Secoagroclavine , 1981 .

[19]  M. Somei,et al.  The Chemistry of Indoles. XIII. Syntheses of Substituted Indoles carrying an Amino, Nitro, Methoxycarbonyl, or Benzyloxy Group at the 4-Position and Their 1-Hydroxy Derivatives , 1981 .

[20]  T. Onishi,et al.  A FACILE SYNTHESIS OF 4-HYDROXYINDOLE VIA ELECTROCHEMICAL OXIDATIVE C–C COUPLING , 1980 .

[21]  I. Stamos.  A Convenient Preparation of Ethyl 5,6-Dimethoxyindole-3-acetate , 1980 .

[22]  W. C. Still,et al.  Rapid chromatographic technique for preparative separations with moderate resolution , 1978 .

[23]  D. B. Repke,et al.  Psilocin analogs. 1. Synthesis of 3-[2-(dialkylamino)ethyl] -and 3-[2-(cycloalkylamino)ethyl] indol-4-ols , 1977 .

[24]  J. Suh,et al.  A Novel Synthesis of 2,3-Disubstituted Indoles. A Study of the Reductive Cyclizations of Some 3-Substituted 2-(4,5-Dimethoxy-2-nitrophenyl)acrylonitriles1a , 1965 .

[25]  R. M. Herbst,et al.  Tetrazole Analogs of Plant Auxins1 , 1959 .

[26]  C. G. Force,et al.  Synthesis of Indoles by Catalytic Reduction of o-Nitrobenzyl Cyanides , 1958 .

[27]  G. N. Walker.  Synthesis of 5,6-Dimethoxyindoles and 5,6-Dimethoxyoxindoles. A New Synthesis of Indoles , 1955 .