Chiral Synthesis of 3,4 - difluoro - N - {2 - (2-fluoro-4 - yodofenil) amino - 6 - 1 - (4-methoxyphenyl) 2,3-dihydroxy propyl cyclopropane Sulfonamides

摘要

A method for preparing enantiomers Enantioselective (S) - and (R) - N - {3,4 - difluoro - (2 - [2-fluoro-4 - yodofenil) amino] - 6 - [1 - (4-methoxyphenyl) 2,3-dihydroxy propyl] - cyclopropane sulfonamide, formulas and (S) - 14 (R) - 14, Intermediate Compounds, and the use of these compounds as intermediaries for the Prep These araciu00f3n enantiomers (S) - and (R) - N - {3,4difluoro - (2 - [2-fluoro-4 - yodofenil) amino] - 6 - [1 - (4-methoxyphenyl) 2,3-dihydroxy propyl] cyclopropane sulfonamide.Claim 1, characterized in that: a compound is selected from: bromide 1 - {[(4S) - 2,2 Dimethyl 1,3 - dioxolan - 4-yl] methyl cyclopropane sulfonyl} formula (S) - 10 - BR; bromide 1 - {[(4R) - 2,2 Dimethyl 1,3 - dioxolan - 4-yl] methyl cyclopropane sulfonyl} Formula (R) - 10 - BR; 1 - {[(4S) - 2,2-dimethyl - 1.3 - dioxolan - 4-yl] methyl} cyclopropane sulfonate Potassium formula (S) - 7 '; 1 - {[(4R) - 2,2-dimethyl - 13 - dioxolan - 4-yl] methyl} cyclopropane sulfonate Potassium formula (R) - 7 '; 1 - {[(4S) - 2,2 Dimethyl 1,3 - dioxolan - 4-yl] methyl} formula cyclopropane sulfonate butyl (S) - 6; 1 - {[(4R) - 2,2 Dimethyl 1,3 - dioxolan - 4-yl] methyl} cyclopropane sulfonate Butyl formula (R) - 6; 1 - [(2S) - 2,3-dihydroxypropyl Cyclopropane sulfonate formula] butyl (S) - 5, 1 - [(2R) - 23 - dihydroxypropyl) cyclopropane sulfonate Butyl formula (R) - 5, 1 - [(2S) - 2 - oxiran - ylmethyl] Formula cyclopropane sulfonate butyl (S) - 4 - [(2R) - 1 - 2 - ylmethyl] oxiran cyclopropane sulfonate Butyl formula (R) - 4; 1 - [(2S) - 3-chloro-2-hydroxypropyl sulfonate Butyl Fu00f3rmul cyclopropane] (S) - 3; 1 - [(2R) - 3-chloro-2-hydroxypropyl sulfonate butyl] cyclopropane formula (R) - 3; 1 - [(2S) - 2 - {[Tert Butyl (dimethyl) silyl] oxy] - 2-hydroxypropyl] Formula cyclopropane sulfonate butyl (S) - 9A; 1 - [(2R) - 3 - [(tert butyl dimethyl) silyl] oxy] - 2-hydroxypropyl] cyclopropane sulfonate Butyl formula (R) - 9th 1 - [(2S) - 2 - hydroxy - 3 - (Tetrahydro - 2H - piran - 2 - iloxi) propyl] cyclopropane sulfonate Butyl Formula (S) - 9B; 1 - [(2R) - 2 - hydroxy - 3 - (Tetrahydro - 2H - piran - 2 - iloxi) propyl] cyclopropane sulfonate BuTilo formula (R) - 9B.Claim 2: wherein is a method for preparing a compound with the formula (S) - 14, which comprises: (i) The Next Step J: where a compound with the formula (S) - 10 left to react with a compound of the formula (12) in the presence of bromide bromide, e.g. t ETRA - n or - butylammonium bromide Lithium, optionally in the presence of a base such as PyridineOptionally a Solvent, e.g., sulpholane, providing thus a reaction mixture containing a compound with the formula (S) - 13; and then (ii) The Next Step K, which adds an aqueous mineral acid, such as hydrochloric acid, The reaction mixture S containing a compound with the formula (S) - 13To give such a compound with the formula (S) - 14.