Back to results
US 8,476,442 B2Granted
Process for making modulators of cystic fibrosis transmembrane conductance regulator
AssigneeVertex Pharmaceutical Incorporated
InventorsJohn DeMattei, Adam R. Looker, Bobbianna Neubert-Langille, Martin Trudeau, Stefanie Roeper, Michael P. Ryan, Dahrika Milfred Lao Yap, Brian R. Krueger, Peter D. J. Grootenhuis, Fredrick F. van Goor, Martyn C. Botfield, Gregor Zlokarnik
Life of this patent
Estimating the term…
Abstract
The invention provides a process for the preparation of a compound of Formula 1, comprising coupling a carboxylic acid of Formula 2 with an aniline of Formula 3 in the presence of a coupling agent.
Claims13
A process for the preparation of a compound 34
- comprising:
- (a) reacting compound 26
- with compound 32
- in the presence of propane phosphonic anhydride and pyridine using 2-methyl tetrahydrofuran as the solvent, wherein the reaction temperature is maintained between about 42° C. and 53° C., and wherein the reaction is allowed proceed for at least 2 hours, to produce compound 33
- (b) treating compound 33 with NaOMe/MeOH in 2-methyl tetrahydrofuran;
- and
- (c) forming a slurry of compound 34 in a mixture of acetonitrile and water.
4 more elements
A process for the Preparation of a compound 34
- comprising the steps of
- (a) reacting compound 26
- with compound 32
- in the presence of 2-propane phosphonic anhydride and pyridine using 2-methyl tetrahydrofuran as the solvent, wherein the reaction temperature is maintained between about 42° C. and 53° C., and wherein the reaction is allowed proceed for at least 6 hours, to produce compound 33
- (b) treating compound 33 with NaOMe/MeOH in 2-methyl tetrahydrofuran;
- (c) adding a solution of 1.2 M HCl to the reaction mixture, thereby forming a biphasic solution;
- (d) separating the organic layer from the biphasic solution;
- (e) adding a solution of 0.1 M HCl to the organic layer, thereby forming a biphasic solution;
- (f) separating the organic layer from the biphasic solution;
- (g) reducing the amount of solvent in the organic layer by 50% using distillation;
- (h) increasing the volume of the organic layer by 100% by adding acetonitrile;
- (i) performing step (g) through step (h) two additional times;
- (j) adding water to the organic layer to form a slurry of compound 34 in a mixture having a ratio of 9:1 of acetonitrile to water;
- (k) heating the slurry to a temperature between 73° C. and 83° C. for at least 3 hours;
- (l) cooling the slurry to a temperature between 20° C. and 25° C.;
- and
- (m) filtering and removing solid matter from the slurry.
14 more elements
A process for the preparation of a compound 34
- comprising:
- (a) reacting compound 26
- with compound 32
- in the presence of propane phosphonic anhydride and pyridine using 2-methyl tetrahydrofuran as the solvent, wherein the reaction temperature is maintained between about 42° C. and 53° C., and wherein the reaction is allowed proceed for at least 2 hours, to produce compound 33
- (b) hydrolyzing the methoxycarbonyl protecting group from the phenolic oxygen atom of Compound 33 by treating compound 33 with NaOMe/MeOH in 2-methyl tetrahydrofuran to provide Compound 34;
- and
- (c) forming a slurry of compound 34 in a mixture of acetonitrile and water to provide Compound 34 in a pure form.
4 more elements
Dependencies are inferred from the claim text.