合成路线:Bromination of methyl 3-methoxy-4-methylbenzoate (I) with N-bromosuccinimide in the presence of catalytic amounts of 2,2'-azabisisobutyronitrile in chlorobenzene yields benzylic bromide (II).This compound is coupled with 5-nitroindole via treatment with Ag2CO3 in toluene to afford methyl 4-(5-nitroindol-3-ylmethyl)-3-methoxybenzoate (III).N-Methylation of ester (III),using NaH and MeI in DMF,followed by hydrolysis with NaOH in aqueous THF,affords 4-(5-nitro-1-methylindol-3-ylmethyl)-3-methoxybenzoic acid (IV).Conversion of acid (IV) to the sulfonimide derivative (V) is achieved by sequentially treating (IV) with: (i) SOCl2 plus a catalytic amount of DMF in dichloromethane and (ii) o-tolylsulfonamide and 4-(N,N-dimethylamino)pyridine (DMAP).This intermediate sulfonimide is isolated as the DMAP salt (V),which is converted to ICI 204219 via treatment with H2 over Pd/C in alkaline aqueous methoxyethanol,followed by acylation with cyclopentylchloroformate.
参考文献标题:A physical form of N-[4-[5-(cyclopentyloxycarbonylamino)-1-methyl-indol-3-ylmethyl]-3-methoxybenzoyl]-2-methylbenzenesulfonamide,a process for its preparation and pharmaceutical compsns.containing it
文献作者:Edwards,M.P.; Sherwood,J.D.(AstraZeneca plc)
参考来源:EP 0490649; US 5294636
合成路线:Bromination of methyl 3-methoxy-4-methylbenzoate (I) with N-bromosuccinimide in the presence of catalytic amounts of 2,2'-azabisisobutyronitrile in chlorobenzene yields benzylic bromide (II).This compound is coupled with 5-nitroindole via treatment with Ag2CO3 in toluene to afford methyl 4-(5-nitroindol-3-ylmethyl)-3-methoxybenzoate (III).N-Methylation of ester (III),using NaH and MeI in DMF,followed by hydrolysis with NaOH in aqueous THF,affords 4-(5-nitro-1-methylindol-3-ylmethyl)-3-methoxybenzoic acid (IV).Conversion of acid (IV) to the sulfonimide derivative (V) is achieved by sequentially treating (IV) with: (i) SOCl2 plus a catalytic amount of DMF in dichloromethane and (ii) o-tolylsulfonamide and 4-(N,N-dimethylamino)pyridine (DMAP).This intermediate sulfonimide is isolated as the DMAP salt (V),which is converted to ICI 204219 via treatment with H2 over Pd/C in alkaline aqueous methoxyethanol,followed by acylation with cyclopentylchloroformate.
参考文献标题:Evolution of a series of peptidoleukotriene antagonists: Synthesis and structure/activity relationships of 1,3,5-substituted indoles and indazoles
文献作者:Aharony,D.; Snyder,D.W.; Keith,R.A.; Shapiro,H.S.; Matassa,V.G.; Maduskuie,T.P.Jr.; Hesp,B.; Krell,R.D.
参考来源:J Med Chem 1990,33(6),1781
合成路线:Bromination of methyl 3-methoxy-4-methylbenzoate (I) with N-bromosuccinimide in the presence of catalytic amounts of 2,2'-azabisisobutyronitrile in chlorobenzene yields benzylic bromide (II).This compound is coupled with 5-nitroindole via treatment with Ag2CO3 in toluene to afford methyl 4-(5-nitroindol-3-ylmethyl)-3-methoxybenzoate (III).N-Methylation of ester (III),using NaH and MeI in DMF,followed by hydrolysis with NaOH in aqueous THF,affords 4-(5-nitro-1-methylindol-3-ylmethyl)-3-methoxybenzoic acid (IV).Conversion of acid (IV) to the sulfonimide derivative (V) is achieved by sequentially treating (IV) with: (i) SOCl2 plus a catalytic amount of DMF in dichloromethane and (ii) o-tolylsulfonamide and 4-(N,N-dimethylamino)pyridine (DMAP).This intermediate sulfonimide is isolated as the DMAP salt (V),which is converted to ICI 204219 via treatment with H2 over Pd/C in alkaline aqueous methoxyethanol,followed by acylation with cyclopentylchloroformate.
参考文献标题:Accolate
文献作者:Bernstein,P.R.
参考来源:Drugs Fut 1994,19(3),217
产品链接: CAS No. 107753-78-6››